***We are uncertain of a release date for the CTSI Pilot 2025-2026 RFA. We expect to have more information later this summer regarding a possible Fall 2025 Application process. Please note any awards would be contingent upon BU CTSI Funding. If you have questions please email us at ctsisvcs@bu.edu.
The CTSI provides pilot funding for innovative translational research and the development of research methods at BU that encompasses the translational science spectrum. Our goal of the BU CTSI Pilot Grant Program is to help investigators explore and solve major challenges in translational science and we seek to stimulate individual and team science in all areas of translational research related to the prevention, diagnosis, and management of the human disease. Researchers engaged in translational basic/bench, clinical, biomedical, patient-oriented, implementation, and population health science research are encouraged to apply. The CTSI welcomes applications that are at all levels of the translational science spectrum.
The translational science spectrum shows the stages of translational research. The stages do not happen in a straight line or in one direction. Each stage builds upon and informs the others. At all stages, our staff and grantees come up with new approaches, prove their usefulness and share the findings. Patient involvement is a key feature of all stages in translation.
The BU CTSI will provide pilot awards in the amount of up to $25,000 per year. All pilot awards will be required to have the necessary and required regulatory approvals prior to the start of each pilot project (IRB and IACUC- internal and external (NIH) requirements).
2024 CTSI Translational Science Integrated Pilot Awards
Applicants to the BU CTSI Pilot Grant Program are required to have a primary faculty appointment at Boston University, and the research to be conducted must be based at Boston University, Boston Medical Center, VA Boston Health Care or any of their affiliated hospitals and health centers. Faculty with co-appointments at BU and BU/BMC affiliated institutions are also eligible to apply. In particular we encourage early investigators to apply, including those with institutional or individual mentored research awards from NIH or Foundations. Recipients of previous BU CTSI awards are eligible to apply for awards to support new research projects, providing awards are at least two years apart with evidence of successful completion and productivity with the prior award. Individuals from under-represented groups are highly encouraged to apply. Applications from interdisciplinary teams of investigators are highly encouraged. Collaborations with investigators outside of the BU/BMC and affiliates are allowed, though justification should be provided. To search for BU collaborators, refer to BU Profiles or send a request to the BU CTSI Navigator team at ctsisvcs@bu.edu. All applications must include the following documents: Applications will be reviewed by the BU CTSI Scientific Review Committees comprised of faculty with relevant expertise analogous to the NIH review process (with a focus on Significance, Innovation, Approach, and Investigators). Specific review criteria include, but are not limited to: Although not required that applicants be early-stage investigators, the review process will consider career development. We encourage inquiries regarding the BU CTSI Pilot Grant Program and welcome the opportunity to answer questions. Direct your questions to: Andrew Henderson, PhDCriteria for Eligibility
Application Process
Where to Direct Inquiries
Elisha Wachman, MD
Department of Pediatrics
Co-Director, Pilot Grant Program, BU CTSI
E-mail: Elisha.Wachman@bmc.org
Department of Medicine, Infectious Diseases
Co-Director, Pilot Grant Program BU CTSI
E-mail: hender@bu.eduAdministrative Contact:
Hubert Wong
Director of Finance & Operations, BU CTSI
617.358.7553 (ph)
ctsipilots@bu.edu
2024 Integrated Pilot Grant Awardees
Funded by BMC |
Placental Repository to Improve Infant Lung Outcomes in Preeclampsia
The BMC PRIME study is a longitudinal prospective study evaluating placental secreted proteins from preeclamptic pregnancies. Preeclampsia is a hypertensive disorder of pregnancy that is strongly associated with neonatal lung and gut disorders for premature infants. Through the PRIME study, Dr. Taglauer will seek to identify unique signaling proteins from preeclamptic placentas that are connected with pathways of lung and gut developmental injury. The PRIME study will also be creating a highly valuable biorepository of preeclamptic placental samples that will be available for collaborative studies.
Dr. Elizabeth Taglauer is a neonatologist and placental biologist who has developed a unique niche as a physician-scientist to explore how the intrauterine environment can be optimized to improve neonatal outcomes. In her faculty research at Boston Medical Center, Dr. Taglauer is applying her placental expertise to examine how perinatal exposures impact neonatal outcomes. The main focus of her work is on the antenatal determinants of neonatal lung and gut disease, seeking to understand how human placental dysregulation impacts fetal lung and gut development. Dr. Taglauer’s research incorporates human placental components with translational human developmental model systems with a long-term goal of optimizing infant development and health outcomes.
Funded by BU CTSI |
Validity, Acceptability, and Utility of Electronic Health Record Household Linking
Although there is common consensus that clinicians and the health system need to focus on providing care for households, there are few tools that facilitate this process, particularly in the electronic health record. Recently, research methods have been developed to link household members together in the electronic health record. These tools afford a promising opportunity to better direct care towards families as a whole, and to study the effects of family-level care. However the validity, effectiveness, and acceptability of these tools haven’t been well-studied, leaving a major gap in our ability to translate these research tools into clinical care. In this project, we plan to evaluate how effective household linkage tools are by interviewing patients about their household membership, and cross-referencing their descriptions of household composition with household membership gathered through electronic health record linking. We will focus on a key disease that clusters within families, but for which there are few family-level care options: latent tuberculosis infection. We will also interview patients and clinicians about the acceptability of existing and anticipated household linking tools to better understand how these tools could be used, and to anticipate potential challenges to implementing them. The steps we’re taking in this project provide necessary groundwork for translating a promising research tool—electronic health record household linking—to the clinic and the bedside.
Meet the Team
Dr. Jeffrey Campbell is an Assistant Professor of Pediatrics in the Department of Pediatrics/Section of Pediatric Infectious Diseases at the Boston University Chobanian and Avedisian School of Medicine.
Dr. Karen Jacobson is an Associate Professor of Medicine in the Section of Infectious Diseases at the Boston University Chobanian and Avedisian School of Medicine and Boston Medical Center.
Dr. William G. Adams is an epidemiologist, medical informatician, and practicing pediatrician at Boston Medical Center (BMC). He is also Professor of Pediatrics and serves as Director of BU-CTSI Biomedical Informatics for Boston University and Director of Community Health Informatics for the Boston HealthNet, an urban integrated health delivery system. His primary research is focused on developing and evaluating information technology (IT)-based solutions for improving the quality of health and healthcare for urban populations. His foci include electronic health records (EHR) for research, state-wide registries, decision support, patient-centered health IT and clinical data warehousing for quality improvement and comparative effectiveness research.
Dr. Jessica Haberer received her medical degree from Yale University and a master’s degree in Health Services Research from Stanford University. She trained in Internal Medicine at the University of California San Francisco and, early in her career, worked for the William J. Clinton Foundation HIV/AIDS Initiative. Since 2008, she has worked at the Massachusetts General Hospital and Harvard Medical School as a physician-researcher. Her current work focuses on HIV prevention, implementation science, and data science with collaborations primarily in East and South Africa. Dr. Haberer also serves as the Director of Research at the MGH Center for Global Health and is committed to active mentorship, promotion of diversity in the research workforce, and equity in global health research partnerships.
Dr. Robert Horsburgh, Jr., is Professor of Epidemiology, Biostatistics, Global Health and Medicine at Boston University. He is an experienced tuberculosis (TB) clinician whose research has focused on TB epidemiology and clinical trials. He has served as Co-Chairman of the U.S. TB Trials Consortium and the U.S. TB Epidemiologic Studies Consortium. He is currently a member of the Board of Directors of the International Union Against Tuberculosis and Lung Disease and Chairman of the Steering Committee of RESIST-TB, an international organization that advocates for global expansion of treatment for Drug-resistant TB (http://www.resisttb.org/).
Dr. Heather Hsu is an Assistant Professor of Pediatrics and Scientific Director of the Boston Medical Center Clinical Data Warehouse for Research.
Dr. Helen E. Jenkins‘ research focuses on the epidemiology of tuberculosis. She is interested in what we can learn about TB epidemiology using routinely-collected data sources and has collaborations in South Africa, Ukraine, and Peru. She is also interested in pediatric TB and the spatial epidemiology of TB.
Dr. Vishakha Sabharwal is a Pediatric Infectious Diseases provider at Boston Medical Center who works in the BMC TB clinic and manages and treats children with TB disease and infection. She has collaborated closely with Dr. Campbell over the past few years and most recently in the TB household linkages to study household clustering of TB infection.
A soft-foldable Robotic Eetractor with Integrated Pressure Sensing to Reduce Tissue Trauma in Neurosurgery and Skull Base Surgery
Brain retraction systems are frequently required to achieve surgical exposure of deep-seated brain lesions. Retraction, however, can cause localized stress areas and is associated with complications that include brain edema, vascular compromise causing ischemia, and direct damage to the surrounding cortex.
This pilot project will focus on the design, development, and evaluation of a novel soft robotic neurosurgical retractor to tackle current clinical barriers in neurological surgery and skull base surgery. The proposed system is designed to facilitate neurosurgery by creating a minimally invasive surgical workspace in the brain (through expansion and unfolding of pneumatically driven origami-inspired soft robotic actuators) and monitor robot/tissue interaction (via soft capacitive pressure sensors).
This soft robot provides the capability to tune the amount of tissue retraction via actively expanding and contracting its structure by controlling its internal actuation state, and continuously monitor its interaction with the surrounding environment (i.e., brain tissue) while informing the surgeon. The purpose of this device is to address critical unmet needs within the world of brain tumor surgery, such as increasing safety and the depth of access in deep-seated tumor brain locations, improving navigability within the brain, and enabling surgeon awareness during the procedure.
Meet the Team
Dr. Sheila Russo is an Assistant Professor in the Department of Mechanical Engineering and the Division of Materials Science and Engineering at Boston University (BU). She received her Ph.D. degree at the BioRobotics Institute, Sant’Anna School of Advanced Studies, Italy. She completed her postdoctoral training at the Harvard John A. Paulson School of Engineering and Applied Sciences and the Wyss Institute for Biologically Inspired Engineering. She is the founder and director of the Material Robotics Laboratory at BU. Her research interests include medical and surgical robotics, soft robotics, origami-inspired mechanisms, sensing and actuation, and meso- and micro-scale manufacturing techniques. In 2020 she received the NIH Trailblazer Award for New and Early Stage Investigators.
Dr. Anand Devaiah is a Professor in the Departments of Otolaryngology, Neurological Surgery, and Ophthalmology at Boston University and the Boston Medical Center. His research includes development of physical and digital tools in health care; “big data” analytics including the unlocking of data in traditionally siloed repositories; artificial intelligence/machine learning; social determinants of health and health equity; and health care policy. His clinical practice is in anterior and lateral skull base surgery, with special expertise in endoscopic/minimally invasive surgical techniques, head and neck cancer, and complex otology. He is recognized nationally and internationally for his work and holds leadership positions in numerous organizations. He and the teams he works with have been awarded funding from NIH, industry, internal sources, and private sources. In addition to being a resource to students, faculty, and staff interested in entrepreneurship—including offering the Health Care Entrepreneurship elective at the School of Medicine—he serves as an advisor and investor to companies that work in AI, machine learning, and digital health, as well as others in both medical and non-medical industries. He oversees the Electives Curriculum Subcommittee and is a member of the Medical Education Committee in the Boston University Chobanian & Avedisian School of Medicine. He is a retired Medical Officer/Fellow with the Food and Drug Administration and continues working with them through different initiatives. He also serves as part of the Innovation Core in the BU Clinical & Translational Science Institute.
Dr. Urvashi Upadhyay is a board-certified neurosurgeon and director of the Brain Tumor and Skull Base Surgery Program at Boston Medical Center (BMC). Dr. Upadhyay is also a clinical associate professor of Neurosurgery at the Boston University Chobanian & Avedisian School of Medicine and the Associate Program Director for the combined BMC/Beth Israel Deaconess Medical Center (BIDMC) neurosurgery residency training program. She specializes in treating complex brain tumors, meningioma, pituitary tumors, skull base tumors, and trigeminal neuralgia. Dr. Upadhyay’s research interests include intracranial drug delivery, clinical trials in brain tumors, and device development. She collaborates with colleagues from the Massachusetts Institute of Technology (MIT) in the area of drug delivery for brain tumors and at the Material Robotics Lab here at Boston University.
Self-Amplifying RNA Mediated Immunoglobulin Delivery for the Treatment of Breast Cancer
The goal of this project is to leverage a novel self-amplifying RNA (saRNA) technology developed by the Grinstaff and Wong lab to deliver an antibody for the treatment of breast cancer. Success from our work could provide better control of HER2-positive breast cancer progression by reducing tumor volume and extending survival compared to direct intravenous injection of chemotherapy.
Meet the Team
Dr. Wilson Wong is an Associate Professor of Biomedical Engineering at Boston University. His lab has extensive expertise in mammalian synthetic biology, RNA engineering, and immunotherapy.
Dr. Mark Grinstaff is the William Fairfield Warren Distinguished Professor, and a Professor of Biomedical Engineering, Chemistry, Materials Science and Engineering, and Medicine at Boston University. His lab is a leading pioneer in drug delivery, saRNA, nucleic acid chemistry, and biomaterials with successful translation of clinically used products (Abraxane®, OcuSeal®, and Adherus Surgical Sealants®).
A soft Robotic Catheter for Percutaneous Management of Non-compressible Torso Hemorrhage
In the US, injury accounts for over 150,000 deaths and over 3 million injuries per year. Hemorrhage, secondary to traumatic injury, is the leading cause of death of Americans from one to 46 years of age. Noncompressible torso hemorrhage is a leading cause of mortality in patients with trauma.
Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive intervention for temporary control of non-compressible torso hemorrhage originating below the diaphragm to stabilize the patient until they are brought to a hospital for treatment. While it may be lifesaving, the aortic occlusion, can cause severe long term consequences for patients. This project focuses on developing a novel device to enable controllable occlusion of the aorta to allow stabilization of the hemorrhage without completely cutting off blood flow to the lower extremities. The device will be designed to provide a safer alternative to current devices for management of non-compressible hemorrhage. The device will be designed to be easy to use by enabling automation of the hemorrhage control process via robotic technologies.
Meet the Team
Dr. Tom Ranzani received a Bachelor’s and Master’s degree in Biomedical Engineering from the University of Pisa, Italy. He did his Ph.D. at the BioRobotics Institute of the Sant’Anna School of Advanced Studies. In 2014, he joined the Wyss Institute for Biologically Inspired Engineering at the Harvard John A. Paulson School of Engineering and Applied Sciences as a postdoctoral fellow.
He is currently an Assistant Professor in the Department of Mechanical Engineering, Biomedical Engineering, and in the Division of Materials Science and Engineering at Boston University, where he established the Morphable Biorobotics Lab in 2018.
In 2020 he was awarded the NIH Trailblazer Award for New and Early Stage Investigators.
His research focuses on soft and bioinspired robotics with applications ranging from underwater exploration to surgical and wearable devices. He is interested in expanding the potential of soft robots across different scales to develop novel reconfigurable soft-bodied robots capable of operating in environments where traditional robots cannot.
Dr. Jeffrey Siracuse, is Professor of Surgery and Radiology at the Bostin University Chobanian & Avedisian School of Medicine and Associate Chair of Surgery for Quality and Patient Safety at Boston Medical Center. Dr. Siracuse completed general surgery residency at Beth Israel Deaconess Medical Center and a fellowship in Vascular and Endovascular Surgery at New York-Presbyterian Hospital. He was recruited to Boston Medical Center (BMC)/BU Chobanian & Avedisian School of Medicine in 2014. Since 2018, he has served as the Program Director of the BMC Vascular and Endovascular Surgery Fellowship two years later. Dr. Siracuse has been the principal investigator on a large number of research projects, with external support from the NIH and industry. He was the founding Chair of the Society for Vascular Surgery’s Appropriateness Committee and led the development of Appropriateness Use Criteria for the treatment of patients with claudication. As the Medical Director of the Vascular Study Group of New England, which focuses on improving quality and safety in caring for patients with vascular disease, he oversees quality initiatives and the awarding of grants. Dr. Siracuse is the author of more than 250 peer-reviewed journal articles. He has held leadership positions in national vascular surgery organizations and has co-authored multiple practice guidelines. He is an editor of Annals of Vascular Surgery and serves on the editorial board of the Journal of Vascular Surgery.
Funded by BU CTSI CE |
Developing a Family-Based Program to Enhance Autonomy in Adults with Down Syndrome
Down syndrome is the most common chromosomal cause of intellectual disability. Longevity in Down syndrome has increased significantly over the past 30 years, largely due to better care of congenital heart conditions. Most research on Down syndrome in adulthood has focused on the genetic effects of trisomy 21, co-occurring medical conditions, and more recently on pharmacological treatments. The current project focuses on improving daily quality of life of adults with Down syndrome. We will use a community-engaged qualitative approach to develop an online family-based program to promote autonomy in adults with Down syndrome. Building on prior work by our multidisciplinary research team, we will develop Project REACH (Ready to Enhance Autonomy in the Community and Home) – a community-based short-term program, delivered via telehealth, individualized for each family, and focused on skill-building. Through qualitative interviews with adults with Down syndrome, family members, and service providers, we will develop and finalize the content and delivery approach for Project REACH. Specifically, the objectives of this research are to: (1) develop Project REACH for adults with Down syndrome and their family members, (2) inform future implementation of Project REACH by identifying possible barriers, facilitators, scale-up potential, and sustainability in a real-world setting (a local service agency), and (3) prepare a Project REACH program manual and materials to support a subsequent grant application for a clinical trial.
Meet the Team
Dr. Gael Osmond is a Professor in the Department of Occupational Therapy and Associate Dean of Academic Affairs at the Sargent College of Health & Rehabilitation Sciences. Her research, funded by NIMH, NIA, NICHD, the Institute of Education Sciences, and the Deborah Munroe Noonan Memorial Research Fund, focuses primarily on the transition to adulthood in individuals with developmental disabilities, including autism, and how the family, social, community, and school contexts support the wellbeing of adolescents and adults with developmental disabilities. Dr. Orsmond has published more than 65 peer-reviewed publications and book chapters. She is a fellow of Division 33 (intellectual and developmental disabilities/autism) of the American Psychological Association.
Dr. Kristin Long is an Associate Professor in the Department of Psychological and Brain Sciences. Her research investigates individuals’ and families’ experiences of medical illness and disability across the life course in an effort to develop interventions that promote psychosocial functioning within family-centered, culturally-informed models of care. Dr. Long has formed meaningful community partnerships to increase the relevance and community impact of her work. She has led efforts to form local, national, and international collaborations to better understand how to address pervasive unmet needs among individuals with chronic medical conditions or disability and their families. Dr. Long has received funding from the National Institutes of Health and numerous foundations to support her work.
Co-funded by BU CTSI & GSDM |
Radiation Therapy Resistance Promoted by LSD1 in Oral Cancer
Radiation therapy resistance promoted by LSD1 in oral cancer,”. Radiation therapy (RT) has been extensively used for locally advanced cancer. The study showed that only 20-30% of tumors respond to RT. Thus, there is an unmet clinical need to identify radiosensitizers. We have identified an epigenetic regulator, Lysine-specific demethylase 1 (LSD1), which promotes oral and resistance to RT. We expect to evaluate the novel mechanisms that LSD1 promotes DNA damage repair response signaling pathways and inhibition, which could promote sensitivity to RT using a mouse model and pathway analysis. Dr. Truong, who is clinical radiation oncologist and expert in radiation therapy who will provide help in evaluating the doses and relevance of findings for future translation.
Meet the Team
Dr. Manish Bais’s lab focuses on oral cancer and skeletal biology, including temporomandibular joint (TMJ) degeneration and osteoarthritis. He is also a veterinarian by training, specializes in molecular and genetic studies of oral cancer and bone and cartilage remodeling, and develops novel mouse models for translating basic science findings to preclinical studies. He has shared preclinical models with investigators at Boston University and with the wider scientific community.
Dr. Minh-Tam Truong is the Chair and Professor of Radiation Oncology at the Boston University Chobanian & Avedisian School of Medicine and Chief of Radiation Oncology at Boston Medical Center. She received her medical degree from the University of New South Wales, Sydney Australia and completed her residency in Radiation Oncology at New York University Medical Center, her last year as chief resident. She is board certified in Radiation Oncology by the American Board of Radiology. Her specialties include the treatment of head and neck, skin and central nervous system malignancies, as well as benign diseases, including Airway Amyloidosis. Dr. Truong serves on a number of national committees with leadership roles including the Scientific Committee of the American Society for Therapeutic Radiation Oncology (ASTRO), on the head and neck and skin examination committee of the American Board of Radiology (ABR), and currently serves in NRG Oncology (National Surgical Adjuvant Breast and Bowel Project (NSABP), the Radiation Therapy Oncology Group (RTOG), and the Gynecologic Oncology Group (GOG) as the Quality of Life Head and Neck Liaison. She is the Quality of Life Co-Chair on several international head and neck cancer multicenter trials conducted by the NRG Oncology group. She contributes her radiation expertise to the National Cancer Institute’s Adult Oncology Treatment editorial board. She also leads the Cyberknife Radiosurgery program for head and neck malignancies and brain tumors. She is actively involved in promoting clinical research activities at Boston Medical Center, and she was awarded funding as Principal Investigator for an American Cancer Society/Boston University Institutional Grant for the investigation of novel function imaging in head and neck cancer using CT perfusion Imaging in Patients with Head and Neck Cancer undergoing Conformal Radiotherapy. Dr. Truong has also contributed to several Boston Medical Center funded research efforts including two U.S. Army Medical Research and Material Command Office Center of Excellence Program Projects and was a project principal investigator of a department of defense funded study, investigating the role of stereotactic body radiotherapy for recurrent head and neck cancer.
She has published over 100 peer-reviewed scientific articles, editorials, book chapters, and invited reviews.
In 2022, Dr Truong was awarded the Fellow of the American Society of Radiation Oncology for her contributions to the field of Radiation Oncology and service to ASTRO.
Since 2017 to 2024, she has been named Top Doctor in Castle Connolly’s America’s Top Doctors, Exceptional Women in Medicine, and Boston Magazine.
Funded by DOM |
Dialysis Modality Education Access for Latinx Individuals with Kidney Disease
Latinx people experience a two times greater risk of kidney failure compared to non-Latinx White individuals yet are less likely to receive adequate preparation for kidney failure- leading to high rates of urgent dialysis initiation and lower rates of home dialysis and transplant. Pre-dialysis kidney disease education is associated with significantly higher odds of patient-centered preparation for dialysis amongst Latinx individuals. However, Latinx people are less likely to receive adequate kidney dialysis education prior to dialysis, and are more likely to report lack of shared decision-making with their clinician. The aim of our study is to 1) qualitatively evaluate the dialysis modality education experience for Latinx people with kidney disease and their clinicians and 2) establish a community research steering committee to co-design culturally tailored dialysis modality educational materials for Latinx individuals with kidney disease.
Dr. Katherine “Katie” Rizzolo is a clinician-investigator and instructor in the Department of Nephrology at Boston Medical Center. Her research interests center on advocacy for underserved communities disproportionately affected by kidney disease, especially Latinx and immigrant populations. She received her M.D. from Tufts University in Boston, Massachusetts, and completed her residency and chief residency in internal medicine at Maine Medical Center in Portland, Maine. She completed a clinical and research fellowship in nephrology at the University of Colorado in 2023, where her work was supported by their T32 postdoctoral fellowship. While in fellowship, her research aimed to establish the barriers and facilitators to home dialysis for Latinx populations with kidney failure. She is currently a research fellow in Boston University’s Evans Center for Implementation and Improvement Sciences from 2023-2025, and her current research aims to utilize implementation strategies to improves dialysis modality education for Latinx populations with kidney failure. Her long term goal is to become an independent physician investigator utilizing implementation strategies aimed at reducing kidney health disparities for vulnerable populations with kidney disease.
In-depth Profiling of Sickle Cell Disease (SCD) Hematopoietic Stem and Progenitor Cells (HSPCs) to Advance Gene Therapy and Transplantation Approaches
The pilot proposal that was funded by the CTSI complements transformative gene therapy treatments that have recently become available to our sickle cell disease (SCD) patients at BMC. To continue to optimize such treatments and make them safer, more efficacious, and more widely accessible, we will establish a SCD-specific hematopoietic stem and progenitor cell (HSPC) signature. Sickle cell disease is associated with chronic inflammation of the bone marrow, affecting HSPCs residing in that niche. To better understand how this inflammation impacts their function and expression profile, we will perform an in-depth characterization of SCD HSPCs, combining functional, transcriptional and cell surface profiling. This work will form the basis for an updated clinical workflow, enabling more accurate stem cell quantification. This in turn will facilitate further optimizations to gene editing and transplantation procedures in terms of cost, precision and safety profile. Our proposal will also explore ways to expand functional hematopoietic stem cells ex vivo, which will be important to make these emerging cell therapies accessible to SCD patients with advanced disease where mobilizing sufficient stem cells to reach current thresholds for cell therapy can be difficult.
Meet the Team
Dr. Kim Vanuytsel is a stem cell biologist with expertise in developmental hematopoiesis, sickle cell disease and hematopoietic stem cell biology. She is originally from Belgium and obtained her PhD from KULeuven (Leuven, Belgium). She subsequently joined the laboratory of George Murphy at the Center for Regenerative Medicine (CReM) for her postdoctoral work. Since joining the research community at Boston University and Boston Medical Center, she has focused on developing tools and resources that help us understand important concepts in hematopoietic development with the goal of translating this knowledge into the realization of the immense potential that induced pluripotent stem cells (iPSCs) and hematopoietic stem cells hold for disease modeling and regenerative medicine.
As part of the Center of Excellence in Sickle Cell Disease here at Boston Medical Center, serving a large and diverse sickle cell disease patient population, Dr. Vanuytsel is committed to finding better solutions for these patients. Leading her research lab, embedded within the CReM, her goal is to continue to focus on issues at the intersection of stem cell biology, cell therapies and sickle cell disease. Her experience in these diverse but complimentary research fields has equipped Dr. Vanuytsel with a unique perspective and skillset to make meaningful contributions to emerging cell therapies for sickle cell disease patients, and by extension, the field of hematopoietic stem cell transplantation as a whole.
Dr. Jean-Antoine Ribeil, is a French clinical hematologist recognized for his dedication to advancing research in red cell disorders, particularly hemoglobinopathies. With a focus on translational research, he spent over a decade at Necker University Hospital in Paris, leading research programs on erythropoiesis and red blood cell disorders while providing care to adult patients with hemoglobin disorders.
Dr. Ribeil’s work has contributed to the development and implementation of gene therapy protocols for hemoglobinopathies, including the recent FDA approvals of Lentiglobin gene therapy for thalassemia and sickle cell disease (SCD). His investigations have also played a role in hematopoietic stem cell collection studies for gene therapy, including a pioneering study on hematopoietic stem cell collection for sickle cell disease using only plerixafor.
Since May 2021, Dr. Ribeil has served as the Clinical Director of the Sickle Cell Center for Excellence at Boston University Medical Center, where his main aim is to provide exceptional care to improve the quality of life for patients. He also leads the GLOB research group, dedicated to advancing research on hemoglobinopathies and gene therapy with the ultimate goal of making these programs accessible to patients, and improving patient outcomes.
Cardiopulmonary Biomarkers of Systemic Sclerosis
Pulmonary hypertension is a major manifestation of a connective tissue disease known as systemic sclerosis and is a significant cause of mortality for many of these patients. Systemic sclerosis-related pulmonary hypertension is a heterogeneous disease with multifactorial contributions. In this proposal, we investigate the role of cardiac disease using an advanced imaging approach, termed speckle-tracking echocardiography, that measures subclinical myocardial deformation to identify and create a library of associated protein biomarkers in the blood. The goal is to unravel potential mechanistic pathways to explain cardiac contributors to pulmonary hypertension for determining why these patients have such poor clinical outcomes.
Meet the Team
Dr. Justin K. Lui, is a pulmonary and critical care physician and an Assistant Professor of Medicine in the Section of Pulmonary, Allergy, Sleep & Critical Care Medicine. Dr. Lui’s clinical and research interest is in pulmonary hypertension, specifically in systemic sclerosis. Within the Pulmonary Center, he conducts clinical and translational research that is at the intersection of medicine and engineering in applying advanced imaging and data science methodologies for a deep cardiopulmonary phenotyping of this rare disease population to further advance novel diagnostic and therapeutic approaches.
Dr. Andreea M. Bujor, is an Associate Professor of Medicine in the Section of Rheumatology at Boston University Chobanian & Avedisian School of Medicine, and the Associate Program Director for the Rheumatology Fellowship Program. She is a board-certified rheumatologist and physician-scientist who specializes in the care of patients with systemic sclerosis. Dr. Bujor has a research lab within the Arthritis and Autoimmune Diseases Center where she conducts translational research in systemic sclerosis. Dr. Bujor’s research focuses on the interaction between immunity and fibrosis in systemic sclerosis, identification of new biomarkers of disease, and development and validation of novel outcome measures for clinical trials in scleroderma.
Dr. Michael P. LaValley is a Professor of Biostatistics at Boston University School of Public Health, where he teaches courses on meta-analysis, logistic regression, and survival analysis. Dr. LaValley serves as the Research Director of the Boston University Core Center for Clinical Research, is the co-lead of the Analysis Core for the Multicenter Osteoarthritis Study (MOST) and is a Member of the Arthritis and Musculoskeletal and Skin Diseases Clinical Trials Study Section (AMSC) for the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).
2023 Integrated Pilot Grant Awardees
Co-funded by BMC & BU CTSI |
Naltrexone for the Treatment of Cannabis Use Disorder in Pregnancy
The primary objective of their study is to gain pilot data on the relative safety and efficacy of the use of Naltrexone (extended release; trade name: Vivitrol) (NTX) in pregnant persons with cannabis use disorder. In this 1-year prospective cohort study, 14 pregnant people with cannabis use disorder (CbUD) (DSM-V diagnostic criteria) between 14- and 30-weeks’ gestation will be enrolled through Boston Medical Center’s Project RESPECT prenatal clinic. Cannabis use disorder (CbUD) during pregnancy impacts an estimated 6-10% of pregnant individual in the US.1 The COVID-19 pandemic and the legalization of cannabis have contributed to increasing cannabis usage 2. CbUD disproportionally impacts younger individuals of racial minorities with lower educational status, making this a particular relevant issue at Boston Medical Center (BMC).2-3 Cannabis use during pregnancy is associated with adverse perinatal outcomes including increased risk for placental abruption, gestational hypertension, low birth weight, preterm birth, NICU admission, lower APGAR scores, and smaller neonatal head circumference.4 In addition, in-utero cannabis exposure may be associated with altered neonatal brain development.5 Further associations of cannabis use in the perinatal period include challenges in breastfeeding decision making, co-occurrence of CbUD with other substance use disorders (SUDs), and the risk for involvement of child welfare agencies.6-7 Pregnancy is a highly motivating time for individuals to seek treatment for substance use disorders.8 However, there are no well-established pharmacologic treatments for CbUD that are routinely used. One emerging therapy is the medication naltrexone (NTX), which works by blocking the mu-opioid receptors thereby inhibiting the release of dopamine.9 This decreased activity in the mesolimbic dopamine reward pathway attenuates the positive effects of substances of abuse and the development of cravings and dependence.9 NTX is FDA approved as first-line treatment for alcohol use disorder (AUD), and is used increasingly for the treatment of those with opioid use disorder (OUD) with NIH studies of its use in pregnancy for OUD and AUD being led by our team at BMC.10 Cannabis acts on the endogenous cannabinoid receptors which are closely linked with the opioid receptor systems.11-12 Prior studies in non-pregnant individuals utilizing NTX for the treatment of CbUD have hypothesized that NTX acts on both systems, upregulating opioid and cannabinoid receptors. NTX has been trialed for CbUD, demonstrating a decrease in cannabis use in non-pregnant individuals.11,13-14However, NTX has never been trialed in pregnant individuals with CbUD who arguably have more to gain from cannabis reduction to improve maternal and neonatal outcomes.
The primary outcome measure of this study will be quantity of cannabis use, defined by survey and laboratory data assessing cannabis consumption. All key outcome measures are as follows: 1) participant outcomes [cannabis consumption, retention in care, preterm birth, and side effects / adverse events); 2) fetal outcomes (intrauterine growth, fetal anomalies).
Meet the Team
Dr. Kelley A. Saia is an Assistant Professor of Obstetrics and Gynecology at Boston University Chobanian and Avedisian School of Medicine and medical director of Project RESPECT, Substance Use Disorder in Pregnancy Treatment clinic at Boston Medical Center. She is board certified by the American Board of Obstetrics and Gynecology and am a Diplomat of the American Board of Addiction Medicine. In addition to practicing as a generalist in Obstetrics and Gynecology, Dr. Saia has 20 years of specialized experience in managing and treating pregnant persons with substance use disorders. Established in 2006, Project RESPECT is a unique multidisciplinary program designed to stabilize and treat pregnant persons with substance use disorders by combining high risk obstetrical care, psychiatric care, relapse prevention, social services, and peer support. Project RESPECT is a regional and national leader in clinical care for this vulnerable and growing population. In addition to clinical care, Project RESPECT is an academic center for clinical research and education. It has established a robust interdisciplinary research collaboration focusing on substance use disorders in pregnancy, medication for opioid and alcohol use disorder in pregnancy, neonatal abstinence syndrome, genetic and epigenetic factors of addiction and postpartum care for persons in recovery. Dr. Saia’s professional goals focus on the advancement and expansion the field of addiction medicine by furthering scientific research and evidenced based medicine in the treatment of substance use disorders for pregnant and parenting persons.
Dr. Cecily Barber will be graduated as the inaugural Eilene Davidson Grayken OB/GYN Fellow in Addiction Medicine in July 2023. Dr. Barber will join Boston University’s OB/GYN Faculty upon graduation. She brings with her a broad experience in basic science research, health policy and clinical medicine. In 2011, she earned a B.A. in Classics with concentration in Latin and Arabic from Brown University, Providence, RI. She attended the University of Miami Miller School of Medicine (UMMSM), Miami, FL completing her Doctor of Medicine and Master of Public Health. In 2021, Dr. Barber was graduated from Thomas Jefferson University Hospital OBGYN Residency Program in Philadelphia, PA. During her OB/GYN residency at Thomas Jefferson University Hospital, she received the Obstetrics and Gynecology Department’s John B. Franklin Award for Compassion and Humanitarianism. While training in Philadelphia, she developed an interest in healthcare for incarcerated women’s health and published an Obstetric Guideline on patient care within the US penal system. In addition, she focused on (1) addressing provider knowledge and attitudes towards breastfeeding in women with opioid use disorder, (2) investigating racial disparities in methadone dosing, and (3) revising urine drug screen policies. Dr. Barber will pursue research in healthcare disparities, access to medication for opioid use disorder in the incarcerated population and increasing access to Hepatitis C treatment postpartum. Her long-term career goals include establishing new maternal recovery programs in under-resourced areas incorporating clinical practice in obstetrics and gynecology, patient advocacy, program development, research, teaching and health policy reform.
Co-funded by BMC & DOM |
Assessing and Addressing Implicit Bias within Healthcare-acquired Infections (AAIm HI)
Structural racism has resulted in inequities across healthcare. A 2018 report on national healthcare quality and disparities, showed marginalized racial/ethnic groups receive worse care and have worse health outcomes. Healthcare-associated infections (HAIs) are an important measure of quality and a significant cause of morbidity and mortality for hospitalized patients. High-quality studies linking racial bias and HAIs are lacking as are studies of HAI reduction initiatives that specifically target racial inequities. Reducing the incidence of HAIs is a major priority for hospitals and regulatory agencies as federal programs link financial penalties or rewards to achieving HAI benchmark improvement goals. Safety Net Hospitals, which have limited resources to implement improvements, and care for more structurally and medically vulnerable communities than other hospitals, are also more likely to incur financial penalties from those incentive programs and must find ways to improve HAI rates and address inequities. Implicit bias training is becoming more prevalent across healthcare but has not been used to specifically improve a targeted healthcare outcome. This proposal aims to reduce implicit bias in healthcare and innovate the use of implicit bias training to improve specific patient outcomes (i.e.,HAIs) impacted by racial bias.
Meet the Team
Dr. Shana A. B. Burrowes is an Assistant Professor at Boston University Chobanian & Avedisian School of Medicine. Dr. Burrowes is a trained epidemiologist skilled in advanced statistical analysis techniques, which she applies across a diverse set of content areas including antibiotic stewardship, HIV, cardiovascular disease, Hepatitis C, sickle cell anemia, and COVID-19. She has a particular interest in applying her analytical and study design skills to projects of public health importance, with a focus on addressing healthcare inequities in underrepresented populations.
Dr. Cassandra M. Pierre is an Assistant Professor at Boston University’s School of Medicine, the Medical Director of Public Health Programs, the Associate Hospital Epidemiologist at Boston Medical Center, and a member of Boston University’s Center for Emerging Infectious Diseases. Her research is focused on infection prevention in systemically vulnerable populations and the elimination of race-based infectious disease inequities.
Dr. Angelique C. Harris is the Associate Dean for Diversity & Inclusion at the Chobanian & Avedisian School of Medicine, the Executive Director of Faculty Development for BU Medical Campus, and Associate Professor in the Department of Medicine and in the Section, General Internal Medicine. Dr. Harris creates, implements, and leads innovative programs, trainings, and initiatives designed to promote more inclusive working and learning environments for faculty, students, and staff in the academic health sciences and STEMM. An Applied Medical Sociologist, Dr. Harris’s other areas of research include health and community activism, race and ethnicity, gender and sexualities, religious studies, cultural studies, and has conducted extensive research exploring sociocultural constructions of health, illness, and medicine within structurally marginalized communities.
Funded by BU CTSI |
Association between Hip Shape and Hip Symptoms
Osteoarthritis (OA) of the hip poses a substantial economic and personal burden. Structural variants in hip morphology on both the acetabular side (dysplasia) and the femoral side (cam morphology) contribute to increased risk of hip OA. However, most studies have used radiographic hip OA as the outcome measure and focused on standard measures of bone shape (i.e., center-edge angle and alpha angle). The group proposes to address this gap by capitalizing on hip structure and symptom data previously collected as part of the Multicenter Osteoarthritis (MOST) study. The group will analyze long-limb radiographs using both standard measures and statistical shape modeling (SSM) to quantify femoral and acetabular shape. The group will determine the association between hip symptoms (pain) and standard shape measures (Aim 1) and shape variations (Aim 2). Understanding this relationship is critically important as hip symptoms, not hip OA, are linked with an increased risk of all-cause mortality. The resulting knowledge gained will provide valuable information for clinicians and patients considering shape-normalizing surgery. Future studies will include obtaining three-dimensional imaging (CT or MRI scans) to overcome the present limitation of using only a two-dimensional picture (radiograph) of 3-D bone shape; notably, the outcomes of the work proposed here will be an important indicator of whether the more intensive 3-D imaging is warranted.
Meet the Team
Dr. Cara L. Lewis is an Associate Professor in the Department of Physical Therapy within Boston University’s College of Health and Rehabilitation Sciences: Sargent College. She received her Master of Science in Physical Therapy from Washington University in St. Louis. She practiced physical therapy for 4 years before returning to Washington University for her PhD in Movement Science. Dr. Lewis completed a post-doctoral fellowship focused on rehabilitation robotics with Dan Ferris, PhD, at the University of Michigan in Ann Arbor. Dr. Lewis has published several peer-reviewed journal articles on hip joint forces, movement analysis and gait. She has received research funding from multiple sources included the NIH and NSF. Dr. Lewis is currently funded to investigate movement differences in young adults with and without hip pain.
Dr. Elise Morgan is the Maysarah K. Sukkar Professor of Engineering Design and Innovation and the inaugural Director of the Center for Multiscale and Translational Mechanobiology at Boston University. She has faculty appointments in the Department of Mechanical Engineering (primary), the Department of Biomedical Engineering, and the Department of Orthopaedic Surgery.Dr. Morgan received her Ph.D. in Mechanical Engineering from the University of California Berkeley and was a postdoctoral fellow in the Departments of Mechanical Engineering and Surgery at Stanford University. Dr. Morgan’s research group focuses on the mechanical behavior and mechanobiology of skeletal tissues at multiple length scales. Her group uses experimental and computational methods to explore how the deformation and failure behavior of tissues depend on the tissue microstructure; and conversely, how the differentiation and adaptation of tissues and cells are modulated by their mechanical microenvironment. Dr. Morgan is strongly committed to expanding access, opportunity, equity and inclusion for all individuals in science, technology, engineering and mathematics (STEM). In her classroom teaching, academic advising, research supervision, mentoring of trainees and early career faculty, and outreach activities, she seeks to shift the culture of academia and STEM workforces towards embracing mutual differences and celebrating individuals’ authentic selves and unique contributions. Dr. Morgan has received research funding from the NIH, the NSF, and multiple industry sources and private foundations. From 2016-2018, she was the Chair of the Skeletal Biology, Structure, and Regeneration study section of the NIH Center for Scientific Review. From 2015-2022, she was an Associate Editor for the Journal of Biomechanics. She is the recipient of several research awards, including the 2013 Kappa Delta Young Investigator Award from the American Academy of Orthopaedic Surgeons, and is the co-founder of a STEM outreach program, Summer Pathways, for high-school girls. Dr. Morgan currently serves as the Associate Dean for Research and Faculty Development in the College of Engineering. She serves on the editorial board of Bone and is a member of the College of Fellows of the American Institute for Medical and Biological Engineering.
Determining Contributions of Hepatocyte Heterogeneity to ZZ AATD-Associated Liver Disease
Alpha-1 antitrypsin deficiency (AATD) is a common inherited cause of chronic liver disease, without any clinically-available therapies beyond organ transplantation. In the US alone, it is estimated that 100,000 individuals are homozygous for the “Z” mutation (referred to as ZZ), the most common liver disease causing variant. While all hepatocytes express SERPINA1, the gene that encodes AAT, misfolded ZAAT protein has long been recognized to differentially accumulate within the ER of specific hepatocytes which has led to the hypothesis that subsets of hepatocytes are disproportionally affected in disease. However, difficulties in accurately modeling human liver disease at single cell resolution have made it challenging to explore this hypothesis. Additionally, the lack of insight into human hepatocyte heterogeneity and the mechanisms contributing to this heterogeneity, may be critical factors limiting the suitability of human AATD-livers to be treated with future cell-based cell therapies. Dr. Kaserman and Dr. Gouon-Evans will address these clinically translatable questions, leveraging a unique set of resources available on the BU Medical Campus: Boston University is one of 3 sites nationally participating in the Alpha-1 Adult Clinical and Genetic Linkage Study and has performed liver biopsies on 23 ZZ patients over the past 2 years that will be utilized for this study. Furthermore, BU has recently invested in MERSCOPE technology that allows the interrogation of gene expression in fixed tissue samples at single cell resolution. Over the next year, this proposal will apply the first ever integrated advanced RNA sequencing approaches to these rare AATD clinical samples using complementary spatial transcriptomics and single nuclear sequencing to facilitate future therapeutic discovery, with an emphasis on improving cell therapy for this large patient population.
Meet the Team
Dr. Joseph Kaserman received his MD from the University of Vermont, before going on to post graduate training first at Rhode Island Hospital/Brown University for his Internal Medicine residency, followed by a Pulmonary and Critical Care Fellowship at Boston University. It was during his fellowship that he developed a passion for research and the care of patients with Alpha-1 Antitrypsin Deficiency, under the mentorship of Dr. Andrew Wilson, MD and founding Director of The Alpha-1 Center. Upon completion of his fellowship, Dr. Kaserman remained at the Center for Regenerative Medicine (CReM) of Boston University and Boston Medical Center where he is now an Assistant Professor of Medicine in the Section of Pulmonary, Allergy, Sleep, and Critical Care Medicine. Currently, his work focuses on using patient derived induced pluripotent stem cells to model the fundamental mechanisms contributing to the development of liver disease in Alpha-1 patients in order to develop new disease modifying and curative treatments for these individuals.
Dr. Valérie Gouon-Evans is an Associate Professor of Medicine, Section of Gastroenterology, Center for Regenerative Medicine (CReM), Director of the Boston University Liver Biologist (BULB) Program, and Associate Director of the Molecular and Translational Medicine (MTM) PhD Program at BU Chobanian & Avedisian School of Medicine and Boston Medical Center. She received her PharmD, MS, and PhD degrees from Universities of Paris, France. She completed her postdoctoral fellowship at the Albert Einstein College of Medicine, and joined Icahn School of Medicine at Mount Sinai as an Instructor, Research Assistant Professor, and then as an independent Assistant Professor to establish her research program on liver development. Since Dr. Gouon-Evans lab moved to BU Chobanian & Avedisian School of Medicine, Boston Medical Center in 2017, her research interests have aimed to translate her developmental discoveries to harness liver regeneration. The Gouon-Evans Lab is currently developing strategies to treat various liver diseases such as developing cell transplantation strategies to repopulate diseased liver mouse models, promoting intrinsic liver regeneration by harnessing hepatocyte regeneration or inducing differentiation of liver progenitor cells into healthy hepatocytes. All these projects utilize nucleoside modified mRNA complexed to lipid nanoparticles, a technology that her lab has optimized and validated to induce transient yet robust expression of proteins in the liver to alleviate the liver disease.
Individual and Neighborhood-Level Disparities in Buprenorphine Treatment Among BMC Patients
Opioid overdose deaths continue to accelerate with a disproportionate rise among individuals from racial and ethnic minority groups. In addition, individuals from racial and ethnic minority groups exhibit lower receipt of buprenorphine, a key medication in the treatment of opioid use disorder (OUD), relative to Whites. Similar patterns emerge at the neighborhood-level. For example, research has identified associations between neighborhood-level race, ethnicity and income with rates of treatment with buprenorphine and other medications for OUD (MOUD).
The disproportionate rate of opioid-involved overdose in neighborhoods of lower wealth and greater percentage Black or Latino residents demands urgent attention to the intersection of individual and neighborhood-level disparities in OUD treatment. This proposal leverages the Data 4 Equity (D4E) platform, an effort by the BU CTSI Biomedical Informatics Core to strengthen geo-spatial and health disparities research at BUMC. The proposed research aims to describe individual and neighborhood-level disparities in buprenorphine receipt for BMC patients using D4E. This proposal will generate the preliminary work needed for a larger proposal involving more robust geo-spatial analyses of disparities in buprenorphine treatment at BMC.
Meet the Team
Dr. Alyssa Tilhou is a family physician, addiction specialist and health services researcher in the Department of Family Medicine at Boston Medical Center. She is also the Assistant Research Director in the Department of Family Medicine. Her research focuses on access and utilization of primary care and substance use services in low-income populations. Dr. Tilhou completed her medical education and doctorate in Population Health Sciences at the University of Texas Medical Branch, residency in family medicine at the Mountain Area Health Education Center in Asheville, NC, and a fellowship in Addiction Medicine at the University of Wisconsin. She is supported by a K08 from the National Institute on Drug Abuse.
Dr. William G. Adams is an epidemiologist, medical informatician, and practicing pediatrician at Boston Medical Center (BMC). He is also Professor of Pediatrics and serves as Director of BU-CTSI Biomedical Informatics for Boston University and Director of Community Health Informatics for the Boston HealthNet – an urban integrated health delivery system. His primary research is focused on developing and evaluating information technology (IT)-based solutions for improving the quality of health and healthcare for urban populations. His foci include electronic health records (EHR) for research, state-wide registries, decision support, patient-centered health IT and clinical data warehousing for quality improvement and comparative effectiveness research.
Dr. Katherine R. Standish is a clinician and researcher in the Department of Family Medicine at Boston University and is co-founder of the Breastfeeding Equity Center at BMC. Her research addresses breastfeeding services and interventions in marginalized and high-risk populations including dyads impacted by maternal substance use. Dr. Standish studied medicine at Yale University, completed residency training and a primary care academic fellowship at Boston Medical Center, and earned an MS in Epidemiology at Boston University School of Public Health. Prior to studying medicine, she worked in epidemiologic and community-based participatory research on opioid use disorder and infectious diseases in the U.S., Mexico, and Nicaragua.
Dr. Marc Larochelle is an Associate Professor of Medicine at the Boston University School of Medicine and a clinician investigator in the Section of General Internal Medicine at Boston Medical Center. Dr. Larochelle’s clinical and research interests focus on the safety of opioid prescribing and the recognition and treatment of opioid use disorders. As a health services researcher, he aims to leverage insights from large data sources and translate the findings into interventions that improve the quality and value of health care delivered. He is a buprenorphine-waivered physician with an active outpatient general medicine and addiction practice and also attends on the inpatient addiction consult service at Boston Medical Center. Dr. Larochelle received a BSE from Duke University, an MD from the University of Pittsburgh School of Medicine, and an MPH from the Harvard University School of Public Health. He completed his residency in internal medicine at Johns Hopkins Bayview and a fellowship in general medicine at Harvard Medical School’s Department of Population Medicine.
Pilot Feasibility Study of an In-Home, Body Weight Harness Mobility System for Infants with Down syndrome
The emergence of crawling and walking is significantly delayed in infants with Down syndrome (DS), but the development of independent mobility provides infants with new opportunities for exploring the environment and interacting with objects and people, which are important foundations for early learning. Increasing infant mobility early in development with body weight supported harness systems may support infant exploration, communication, and social interaction. This project will set the stage for the first clinical trial of a mobility-related intervention specifically tailored for infants with DS by testing the feasibility of harness systems with infants and families and identifying measures that will serve as primary outcome variables. Upon completion of this pilot project, Dr. Jana Iverson and Dr. Nicole Baumer will have obtained necessary preliminary data and experience required for an in-home, high-impact clinical trial for infants with DS.
Meet the Team
Dr. Jana M. Iverson is the Dudley Allen Sargent Professor of Pediatric Rehabilitation and Associate Dean for Research for the College of Health & Rehabilitation Sciences: Sargent College at Boston University. Her research, funded by NICHD, NIDCD, and Autism Speaks, focuses primarily on the interface between the development of early motor skills and the emergence of communication and language in neurotypical development and in children with or at risk for developmental disorders. Dr. Iverson has published a co-edited book and more than 100 articles and book chapters. She is on the editorial boards of the Journal of Child Language and Language Learning and Development. Since 1991, she has served as an international investigator at the CNR in Rome, Italy. Dr. Iverson is a Fellow of the Association for Psychological Science.
Dr. Nicole Baumer is a child neurologist / neurodevelopmental disabilities specialist at Boston Children’s Hospital and an Assistant Professor of Neurology at Harvard Medical School. Dr. Baumer is Director of the Boston Children’s Hospital Down Syndrome Program. She completed medical training at Harvard Medical school, pediatrics training at Massachusetts General Hospital, and Neurodevelopmental Disabilities Training at Boston Children’s Hospital. Dr. Baumer also studied Special Education, and has a Masters Degree in Education from Harvard Graduate School of Education. She specializes in treatment of individuals with Down syndrome, Autism, ADHD, and other neurobehavioral disorders. Dr. Baumer’s research involves characterization and diagnosis of neurodevelopmental profiles in Down syndrome, and investigation of educational, behavioral, and medical interventions in neurodevelopmental disorders.
Risk Assessment of Lung Squamous Premalignant Lesions
Lung cancer is the leading cause of cancer death. To increase survival, therapies are urgently needed to intercept the cancer development process and decrease the rate of patients presenting with advanced disease. Lung squamous cell carcinoma (LUSC), the second most common type of non-small cell lung cancer in the US, arises in the epithelial layer of the bronchial airways and is often preceded by the development of bronchial premalignant lesions (PMLs). Approximately 10-50% of high-grade bronchial dysplasia and cases with multiplicity of bronchial dysplasia are likely to progress to invasive LUSC. Also, the presence of persistent or progressive high-grade dysplasia is a marker of increased lung cancer risk, and lung cancers may develop either at the lesion site or at a separate location. There is currently a lack of biomarkers to predict which lesions will progress to LUSC and to predict the risk of lung cancer development anywhere in the lung in patients with PMLs. Development of these biomarkers may improve lung cancer screening by identifying the optimal screening interval and modality (CT and/or bronchoscopy) as well as identify patients for and suggest effective agents for lung cancer interception. The group is currently developing deep learning frameworks using digitized H&E whole slide images (WSIs) of PMLs to predict histologic features and outcome. In this proposal, the group will develop deep learning models using PML WSIs and clinical covariates to predict risk of a lesion progressing to LUSC and a patient-level risk of developing lung cancer.
Meet the Team
Dr. Jennifer E. Beane-Ebel is an Associate Professor of Medicine in the Section of Computational Biomedicine within the Department of Medicine at BUSM. She is a computational biologist with research interests in developing early detection lung cancer biomarkers and understanding biological mechanism of early lung cancer initiation and development.
Dr. Vijaya B. Kolachalama is an Associate Professor of Medicine in the Section of Computational Biomedicine within the Department of Medicine at BUSM. He is a founding member of BU’s Faculty of Computing & Data Sciences and affiliated with the Department of Computer Science. Research interests of his group currently lie at the interface of machine vision, representation learning and domain generalization.
Other Members of the Team
Dr. Eric Burks, Dr. Sarah Mazzilli, & Dr. Ehab Billatos
Target Deconvolution Of Host-Directed Antiviral Rocaglates
The continued spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) warrants discovery of new antiviral therapeutics. To address this need, a team led by Prof. John Porco (PI, BU Chemistry BU-CMD and co-Investigator Prof. Robert Davey (BU-NEIDL) employed a cell-based screen that identified a number of synthetic rocaglates as potent inhibitors of SARS-CoV-2 infection. Rocaglates are a diverse family of plant metabolites with potent anti-neoplastic and anti-infective activities. In the CTSI Integrated Pilot Grant “Target Deconvolution of Host-Antiviral Rocaglates,” a two-phased approach will be used to identify rocaglate host targets that are important for SARS-CoV-2 infection. The approach involves use of a novel thermal proteome profiling assay to identify candidate targets of antiviral rocaglates, followed by a targeted CRISPR screen to disrupt candidate targets and evaluate impact on infection efficiency.
Meet the Team
Dr John A. Porco joined the Department of Chemistry at Boston University in 1999 as Assistant Professor after working in industry and was promoted to Professor of Chemistry in September 2004. Since 2014, John has been the Director of the Center for Molecular Discovery (BU), an integrated infrastructure for the discovery of small molecule chemical probes and medicinal chemistry. The Porco Laboratory develops new synthetic methodologies for chemical synthesis of bioactive molecules and complex natural products. The laboratory also seeks to establish innovation in collaborative, translational science to study the biological properties and mode of action (MoA) of target molecules including collaborative work with the Davey lab. The Porco lab is interfaced with the nearby Boston University Center for Molecular Discovery (BU-CMD) and the newly establish BU Target Discovery Lab (BU-TDL).
Dr. Robert Davey is a Professor in the Department of Microbiology at Boston University Medical Center (BUMC) and a member of the NEIDL, BU’s BSL4 laboratory. With a rich academic background, he spent seven years at the Texas Biomedical Research Institute and over a decade at the University of Texas Medical Branch-Galveston. Renowned for his expertise in virology, Davey has dedicated his research to the study of viral infections, focusing on filoviruses such as the Ebola virus and, more recently, coronaviruses. His team’s work in the high biocontainment lab has not only led to the development of therapies, including an FDA-approved antibody therapy for Ebola virus disease, but has also provided valuable insights into the mechanisms of viral infections. Collaborating with excellent chemists, such as Drs. Porco and Brown in the BU Center for Molecular Discovery, he has made notable strides in understanding host-virus factor interactions and is working to apply these findings to drug discovery and development against lethal pathogens.
Co-funded by BU CTSI & DOM |
Big Data and Team Science Approach to Identify Novel Molecular Pathway and Mechanism of Action of a New Drug for Patients with Chronic Kidney Disease
Chronic kidney disease (CKD) affects approximately 13% of the global population, yet there is currently no kidney podocyte-specific anti-proteinuric treatment available, highlighting a significant global medical need. This pilot project aims to address this gap by identifying a novel molecular pathway and mechanism of action for a potential drug to treat proteinuria and CKD, using a team science approach. The project will leverage pathological and single-cell transcriptome data from animal models to gain a deeper understanding of the underlying mechanisms of potential candidate drugs. Furthermore, it will validate and translate these findings using CKD patient data and samples collected as part of the KPMP and BKBC studies. Successful completion of this project has the potential to yield new therapeutics targeting novel drug targets for CKD and proteinuria.
Meet the Team
Dr. Chao Zhang is an Assistant Professor of Computational Biomedicine in the Department of Medicine at Boston University School of Medicine. As an interdisciplinary researcher, he has a background in systems biology, statistics, machine learning, software engineering, and especially in next-generation sequencing analysis. His current research is centered around the investigation of aging-related and chronic diseases, including chronic kidney disease, Alzheimer’s disease, and degenerative joint diseases. Through the use of computational methods, Dr. Zhang aims to develop innovative deep-learning approaches to analyze the single cell level molecular data, providing valuable insights into disease mechanisms. Furthermore, he integrates clinical data with molecular data to enhance disease diagnosis and treatment strategies.
Dr. Weining Lu is an Associate Professor of Medicine, Pathology & Laboratory Medicine and a Principal Investigator in the Nephrology Section of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. The primary research interests of Dr. Lu’s laboratory are focused on basic, pre-clinical, and translational research of the kidney and urinary tract development, congenital anomalies of the kidney and urinary tract, podocyte biology and injury, ROBO/SLIT signaling, and chronic proteinuric kidney disease. In recognition of his seminal contribution to the development of a potential new drug for chronic proteinuric kidney disease in collaboration with Pfizer, Dr. Lu was named the 2019 Boston University “Innovator of the Year,” an award bestowed annually on a faculty member who “translates his/her world-class research into inventions and innovations that benefit humankind.” Dr. Lu is a fellow of the American Society of Nephrology (ASN) and the International Society of Nephrology (ISN). He is also a member of the NIH grant review study sections. Dr. Lu is currently an Academic Editor of the scientific journal PLOS ONE. He received his medical degree from Zhejiang University School of Medicine and his graduate degree from Northeastern University Bouve College of Health Sciences. Dr. Lu completed his clinical residency training in the Second Affiliated Hospital of Zhejiang University School of Medicine and his postdoctoral training in the Renal Division and Genetics Division at Brigham and Women’s Hospital, Harvard Medical School.
Dr. Sudhir Kumar is an Assistant Professor of Medicine in the Nephrology Section, Department of Medicine at Boston University School of Medicine. His research work focuses on Slit-Robo signaling in kidney diseases and podocyte biology and ZEB2 signaling in kidney development and diseases using animal models. Dr. Kumar received his Ph.D. from Ludwig Maximilians University Munich, Germany and completed his postdoctoral training in Dr. Weining Lu’s lab, Nephrology Section at Boston University School of Medicine.
Dr. Sushrut S. Waikar received a BA in English and Neuroscience at Amherst College, his MD at Yale, and an MPH at Harvard. He is the Norman G. Levinsky Professor of Medicine at Chobanian and Avedisian School of Medicine and Chief of Nephrology at Boston Medical Center. Dr. Waikar’s research interests and active projects include epidemiologic, translational, and interventional studies to address novel and clinically important questions in nephrology. Current areas of investigation include optimal diagnostic testing in acute kidney injury and chronic kidney disease; biomarkers of kidney pathology and kidney fibrosis; the identification of relevant targets for interventional trials in kidney disease; and randomized controlled trials. He is a Principal Investigator of several NIH grants, including the Kidney Precision Medicine Project (U01 DK133092), Multi-omics and Chronic Kidney Disease: Correlation with Histology (R01 DK108803), Discovery Science Collaborative for CKDu (U01 DK130060), NAD Augmentation to Treat Diabetic Kidney Disease: A Randomized Controlled Trial (U01AG076789) and The Boston University Kidney and Medical Engineering Program (BU-KIDMEP, R25 DK128858).
Funded by DOM |
Benchmarking Intra-tumor Heterogeneity Approaches in Aggressive Breast Cancer
To date, there have been little to no studies to date that have mapped intra-patient tumor heterogeneity and compared how this is effectively maintained in ex vivo models in a statistically rigorous manner. Here, we aim to make usage of operational clinical pipelines and advancements in spatial, single-cell and experimental modeling techniques that we have established in our labs to address this unmet need and to quantitatively describe the levels and modeling reproducibility of intra-tumor heterogeneity in patients with aggressive breast cancer. To evaluate the significance and limitations of current state-of-the-art intra-tumor modeling approaches, we propose the following aims: 1) Map and document intra-tumor breast cancer heterogeneity using an ultra-resolved spatial multiplexing technology (MERFISH); and 2) Determine how existing patient-derived organoid models recapitulate the original TME diversity at the single-cell level. These studies are essential to safeguard our precious patient samples which are limited and can typically only be used once. Hence, a thorough understanding of the limitations on which future research conclusions or preclinical screening results are based on will be of crucial importance.
Meet the Team
Dr. Ruben Dries is an Assistant Professor at Boston University School of Medicine (BUSM) in the divisions of Hematology & Oncology and Computational Biomedicine. His lab focuses on implementing novel technologies and computational approaches to create a more holistic view of multi-cellular ecosystems, with a specific emphasis on tissue development and cancer progression. He has a multi-disciplinary background and hands-on expertise to support complex and large-scale biomedical projects. He has received training in dissecting signaling pathways, data analysis, and building innovative computational tools, which are all key to support his innovative research studies. During his graduate studies at K.U.Leuven and Erasmus M.C., he became an expert in systems biology. As a postdoctoral fellow at DFCI, he further deepened his knowledge in genomics, computational biology, and software development. More specifically, he created multiple novel algorithms to work with complex (single-cell) genomics and big data datasets and provided open-source tools to the community. In this role, he has also pioneered the field of spatial transcriptomic data analysis with the creation of an open-source and widely used R package called Giotto. In summary, he has a demonstrated record of successful and productive research projects in multiple extraordinarily and competitive fields. His acquired expertise and experience have prepared him to effectively mentor and guide the next generation of scientists in his lab, where they particularly focus on unraveling the extrinsic factors that determine cancer severity and progression in breast cancer patients. Together with the team of Dr. Naomi Ko, they hope to leverage their new insights to help fight the cancer disparities that are currently seen at Boston Medical Center.
Dr. Naomi Y. Ko is an Associate Professor of Medicine at Chobanian and Avedisian School of Medicine (BUSM) and co-Director of the BMC Breast Cancer Program as a medical oncologist at Boston Medical Center (BMC). Dr. Ko attended Johns Hopkins School of Medicine and School of Public Health to complete her MD MPH, with a focus on health outcomes research for vulnerable populations. After internal medicine residency at Brigham and Women’s Hospital, she arrived for fellowship in hematology/oncology at BUSM/BMC, which allowed Dr. Ko to conduct research in the context of caring for an underserved population within a large safety net institution. She has sought out meaningful projects that are a culmination of her passion for oncology, service to the underserved, and academic research. Her research has been focused on breast cancer inequities and optimal delivery of evidence-based treatment and participation in research for vulnerable, racial/ethnic minority women with breast cancer. She is actively investigating how tumor biology, poverty, communication and treatment influence breast cancer outcomes in diverse breast cancer populations.
Defining a Molecular Signature of Cardiac Dysfunction in Systemic Immunoglobulin Light Chain Amyloidosis
Systemic immunoglobulin light chain (AL) amyloidosis features misfolding of destabilized light chains (LCs) produced by malignant plasma cells in bone marrow. Misfolded LCs become amyloid fibrils that deposit in target organs. Organ dysfunction leads to poorer prognosis of AL amyloidosis than other plasma cell dyscrasias. Specifically, advanced cardiac dysfunction limits treatment options and causes early mortality. Cardiac dysfunction is directly precipitated by: 1) direct effects of destabilized LCs and eventually 2) structural damage from amyloid fibril deposits. Understanding early mechanisms of cardiac dysfunction is key to developing screening methods and treatments critical to improving these outcomes. Therefore, the team seeks to identify and validate a molecular signature for early mechanisms of LC-mediated cardiac dysfunction using patient-derived LCs in a novel disease model of induced pluripotent stem cells.
Dr. Camille Edwards is an Assistant Professor of Medicine at Chobanian and Avedisian School of Medicine (BUSM) at Boston University. She maintains a clinical practice in hematology at Boston Medical Center (BMC) with a specific research interest in plasma cell disorders including systemic immunoglobulin light chain (AL) amyloidosis. She is committed to improving the care of vulnerable patient populations using her translational research platform to address unanswered questions encountered in clinical care. After internal medicine residency, she completed hematology and oncology fellowship at BUSM/BMC, obtaining rigorous training through the comprehensive cancer center and the world-renowned BU Amyloidosis Center. Her current research, a collaboration with the Center for Regenerative Medicine (CReM) and BU Amyloidosis Center, focuses on using patient-derived induced pluripotent stem cell-based models of hematologic malignancies to understand disease biology, study the earliest signs of disease, test treatments, and develop the most promising therapeutic agents for clinical trials.
The Relationship of Intra-articular Mineralization to Synovitis in Knee Osteoarthritis
Knee osteoarthritis (OA) affects a large number of adults in the United States and is a major cause of disability. Current treatments for Knee OA are limited in their ability to prevent disease progression and alleviate symptoms. The failure of OA therapies to date is partly due to not targeting the appropriate at-risk populations. Focusing on a Knee OA subtype, those with intra-articular (IA) mineralization, may lead to more effective treatment through the development of targeted mechanistic approaches. This proposal aims to investigate the relationship between IA mineralization and inflammation (synovitis on MRI) in Knee OA. The study will provide valuable insights into how IA mineralization contributes to inflammation, potentially leading to improved therapies, such as anti-inflammatory treatments, for specific groups of people with Knee OA.
Dr. Jean W. Liew obtained her MD from the University of Texas Medical Branch in Galveston, TX. Following this, she completed her Internal Medicine residency at Oregon Health & Science University in Portland, OR and a rheumatology fellowship at the University of Washington in Seattle, WA. Alongside her fellowship, she earned an M.S. in Epidemiology through the University of Washington School of Public Health. Presently, Dr. Liew serves as an Assistant Professor of Medicine in the Section of Rheumatology at BU. Her clinical research centers around knee osteoarthritis and axSpA.
Funded by BU CTSI Informatics |
Understanding Racial Disparities, Genetic Risk and Phenotypes in Patients with Hypertrophic Cardiomyopathy using Machine Learning Algorithms
The current research interests include studying the interplay between genetics, race, social determinants of health and outcomes in patients with hypertrophic cardiomyopathy followed at Boston Medical Center, the largest safety net hospital in New England. The group aims to study the use of novel machine learning algorithms to help improve the diagnosis of hypertrophic cardiomyopathy using echocardiography.
Meet the Team
Dr. Monica Ahluwalia received her MD at Robert Wood Johnson Medical School with Distinction in Research, and completed her Internal Medicine Residency, Cardiovascular Medicine Fellowship and Advanced Heart Failure & Transplant Cardiology Fellowship at University of Pennsylvania, NYU School of Medicine and Brigham and Women’s Hospital, respectively, where she received the Baughman Award of Clinical Excellence. Dr. Ahluwalia is currently an Assistant Professor of Cardiovascular Medicine at the Chobanian and Avedisian School of Medicine and Staff Cardiologist at the Boston Medical Center Boston, MA where she is medical director of the Inherited Cardiovascular Diseases Program. She is also an Advanced Heart Failure & Transplant Cardiologist at Brigham and Women’s Hospital in Boston, MA. Outside the University, she is a member of societies including American College of Cardiology, American Heart Association and Heart Failure Society of America.
Dr. Jacques Kpodonu is currently practicing as an NI- funded cardiac surgeon/scientist at Beth Israel Deaconess Medical Center (BIDMC), Assistant Professor of Surgery (Harvard Medical School) and a recent recipient of the 2022 biodiversity fellow leadership program. His research interests are focused at the intersection of cardiac surgery, data science and global health to address cardiovascular health disparities. Along with Emmanuel Agu, a computer science Professor from Worcester Polytechnic Institute, he is co-director of the Cardiovascular Artificial Intelligence Network (CAIN) a network of global researchers with expertise in cardiology, cardiac surgery, global health and data science focused the use of Artificial Intelligence (AI) to democratize cardiovascular care globally particularly in Low- and Middle-Income Countries.
Dr. Emmanuel Agu is currently an NIH-funded professor and scientist in the computer science department at WPI. His research interests are in the areas of computer graphics, mobile computing, and wireless networks. He is especially interested in research into how to use a smartphone as a platform to deliver better healthcare. In collaboration with researchers at WPI and Dr. Jacques Kpodonu, he developed a machine/deep learning tool to estimate left ventricular ejection fraction on echocardiograms. He currently co-directs the Cardiovascular Artificial Intelligence Network (CAIN) with Dr. Kpodonu
Funded by CAMed |
Profiling of Vulnerable Neurons During the Prodromal Stage of Alzheimer’s Disease
During the early presymptomatic stages of Alzheimer’s disease, only a very specific type of neurons involved in new memory formation starts to dysfunction and form proteinaceous aggregates before degenerating. By the time the first clinical symptoms appear, a substantial number of these neurons have already died. State-of-the-art genomics technologies, such as Single-Nucleus RNA-sequencing, have revealed the molecular changes occurring in neurons at advanced stages of the disease. However, previous studies have utilized the brains of individuals who were diagnosed with Alzheimer’s and had already passed away. Dr. Roussarie, Dr. Stein, and Dr. Zhang propose obtaining brain samples from the BU Alzheimer’s disease research center, specifically from individuals with Alzheimer’s lesions who passed away before experiencing any symptoms. These samples will be analyzed using single-nucleus RNA-sequencing to identify very early disease-associated molecular events. Focusing on the presymptomatic stage of the disease will enhance their understanding of disease onset and help identify new therapeutic intervention points.
Meet the Team
Dr. Jean-Pierre Roussarie is an Assistant Professor in the Anatomy & Neurobiology department at the Boston University Chobanian & Avedisian School of Medicine. After studying engineering in Paris, he did a PhD in neurovirology at the Pasteur Institute. He then moved to New York for his postdoctoral training in the laboratory of Dr. Paul Greengard. He started his lab at BU in 2021. His lab studies selective neuronal vulnerability in Alzheimer’s disease.
Dr. Thor D. Stein completed his undergraduate and graduate studies at the University of Wisconsin- Madison where he earned his MD and PhD (neuroscience) degrees. He completed residency training in pathology and fellowship training in neuropathology at Massachusetts General Hospital. He is currently Associate Professor of Pathology at Boston University Chobanian & Avedisian School of Medicine.
Dr. Chao Zhang is an Assistant Professor of Computational Biomedicine in the Department of Medicine at Boston University School of Medicine. As an interdisciplinary researcher, he has a background in systems biology, statistics, machine learning, software engineering, and especially in next-generation sequencing analysis. His current research is centered around the investigation of aging-related and chronic diseases, including chronic kidney disease, Alzheimer’s disease, and degenerative joint diseases. Through the use of computational methods, Dr. Zhang aims to develop innovative deep-learning approaches to analyze the single cell level molecular data, providing valuable insights into disease mechanisms. Furthermore, he integrates clinical data with molecular data to enhance disease diagnosis and treatment strategies.
2022 Integrated Pilot Grant Awardees
Funded by BMC |
Pilot Implementation of an Automated and Personalized Risk Prediction Tool of Life Threatening Mass Effect After Middle Cerebral Artery Stroke
The purpose of this current CTSI pilot study is to collect preliminary data on the effect and feedback on an automated email-based risk assessment tool indicating a patient’s risk of developing Life-Threatening Mass Effect after Middle Cerebral Artery stroke in clinical practice. This proposed project builds on existing personalized clinical risk models by examining features that would enable an effective intervention to support clinical decision-making and potentially improve patient care. Such foundational work is instrumental to bridge the gap between model development and successful implementation. This work will provide the preliminary data to study whether a tailored risk prediction tool can improve clinician knowledge and treatment decisions. If successful, they will be poised to develop an innovative framework enabling further investigations of successful strategies that not only predict outcome, but impact patient care by supporting clinical decision making for a variety of disease states.
Meet the Team
Dr. Charlene J. Ong is an Assistant Professor of Neurology and Neurosurgery at Boston University, a lecturer at Harvard Medical School, and a clinical neurointensive care physician at Boston Medical Center. She received her undergraduate degree at University of Pennsylvania, her MD at Columbia University and her Master’s in Population Health Sciences at Washington University School of Medicine. Her research focuses on data-driven tools that support clinical decision making and optimize outcome after acute brain injury. She has received foundational support from the NIH in the form of a K23, the American Brain Foundation, Philips-MIT, the Peter Paul Career Development Committee, and the Clinical and Translational Science Institute at Boston University. Her aim is to become an independent investigator in data-driven strategies to support clinical decision making and optimize outcomes after acute brain injury.
Dr. David Greer is Professor and Chair of the Department of Neurology at Boston University School of Medicine and the Richard B. Slifka Chief of Neurology at Boston Medical Center. Dr. Greer is the editor-in-chief of Seminars in Neurology, and the immediate past editor-in-chief for Neurocritical Care on Call. He has authored more than 300 peer-reviewed manuscripts, reviews, chapters, guidelines and books. His research interests include predicting recovery from coma after cardiac arrest, brain death, and multiple stroke-related topics, including acute stroke treatment, temperature modulation and stroke prevention.
SNAP: Supportive Noninvasive Ventilation for Acute Chest Syndrome Prevention for Hospitalized Children with Sickle Cell Disease
Dr. Cohen’s proposed project, “SNAP: Supportive Noninvasive Ventilation for Acute Chest Syndrome Prevention in Children with Sickle Cell Disease” is a mixed-methods study that is intended to provide preliminary data to support a future NIH application. The study will conduct a multicenter Hybrid Effectiveness/Implementation trial to test the hypothesis that the use of noninvasive, bi-level positive airway pressure (BiPAP) ventilation as supportive care for hospitalized pediatric patients with sickle cell disease is 1) effective at preventing the development and progression of acute chest syndrome (ACS), and 2) feasible to implement across a broad range of institutions. The Department of Pediatrics has been using BiPAP as supportive care on the general pediatrics inpatient unit to prevent ACS since 2017. While BiPAP is a safe and effective treatment for ACS when used in the ICU setting, its use as a preventive therapy – specifically in a non-ICU setting – has never been tested. The proposed pilot study will provide critical information to inform the design of a hybrid intervention trial. (Award co-funded with the BU CTSI)
Meet the Team
Dr. Robyn Cohen is the director of the Division of Pediatric Pulmonary and Allergy at Boston Medical Center and Associate Professor of Pediatrics at Boston University School of Medicine. She went to medical school at the Albert Einstein College of Medicine and did her residency in Social Pediatrics at the Children’s Hospital at Montefiore. She completed her pediatric pulmonary fellowship at Boston Children’s Hospital, then went on to pursue a post-doctoral research fellowship in Respiratory Epidemiology at the Channing Laboratory (now the Channing Division of Network Medicine) at Brigham and Women’s Hospital, which included an MPH in Clinical Effectiveness at the Harvard School of Public Health. Her clinical and research interests are in respiratory health disparities in children with a focus on pediatric asthma and sickle cell lung disease.
Dr. Caitlin Neri is an academic pediatric hematologist at Boston Medical Center (BMC) and Boston University School of Medicine (BUSM) with particular interest in treating children with sickle cell disease, multimodal pain management strategies, and supportive care of children with sickle cell disease. She clinically cares for patients in BMC’s Pediatric Sickle Cell program and directs the multidisciplinary Pediatric Pain Clinic at BMC. She is also an Assistant Professor of Pediatrics at BUSM, where she directs a second-year medical student course in hematology and is currently overseeing the hematology content for the upcoming BUSM curriculum redesign.
Dr. Elizabeth Klings is an Associate Professor of Medicine and Director of the Pulmonary Hypertension (PH) Center and the Center for Excellence in Sickle Cell Disease (SCD) at Boston University School of Medicine (BUSM)/Boston Medical Center. She received her BA and MD degrees from New York University, completed her training in pulmonary and critical care at BUSM, and joined the faculty in 2000. Her current research interests include understanding the interplay of venous thromboembolism and PH in SCD. Drs. Cohen and Klings have worked together for almost 10 years and collaborated on a project evaluating the frequency of sleep disordered breathing in adult and pediatric patients in SCD (Worsham CT, et al. Am J Hematol 2017;92:E649-E651.) She is a member of the Medical and Research Advisory Council of the Sickle Cell Disease Association of America and has helped to craft the US-based response to the pandemic. Her research helped to identify the link between COVID-19 and acute chest syndrome (ACS) in SCD. She led the American Thoracic Society (ATS) sponsored Clinical Guidelines for the Diagnosis and Treatment of PH in SCD (AJRCCM 2014) and Workshop for Defining Clinical and Research Priorities in Sickle Cell Lung Disease (Annals of ATS2019). One of the priorities was the need to identify better strategies for prevention of acute chest syndrome, which is a focus of this project.
Toward Noninvasive Imaging Biomarkers of Drug-resistant Epilepsy
The aim is to investigate a novel noninvasive imaging method for the evaluation of blood-brain barrier permeability. Such findings would improve our knowledge about mechanisms of treatment resistance and the care of people with epilepsy. (Award co-funded with the BU CTSI)
Meet the Team
Dr. Myriam Abdennadher is an Assistant Professor of Medicine in the department of neurology at Boston University School of Medicine (BUSM). Sheis a board-certified neurologist, clinical neurophysiologist, and epileptologist, with a focus on drug-resistant epilepsy, neuroimaging of epilepsy, seizure focus localization and epilepsy surgery. Her research focuses on neurophysiologic and brain imaging methods in drug-resistant epilepsy. She is particularly interested in non-invasive MRI methods to better understand drug resistance and to define seizure zone. Her goal is to improve seizure control and quality of life in patients whose seizures don’t respond to medications and who may benefit from surgical treatment.
Dr. Ning Hua is an Assistant Professor of Radiology at Boston University School of Medicine (BUSM). She is an MRI physicist and expert in neuroimaging and cardiovascular imaging. Her current research focuses on using advanced perfusion MRI methods to study vascular dysfunction in brain pathologies. She is particularly interested in the microvascular contribution to epilepsy, Alzheimer’s disease, related neurodegenerations, and the aging brain. Her goal is to develop novel imaging markers for evaluating blood-brain barrier integrity and microcirculation status (permeability, perfusion, flow rate, curvature, etc.) in both clinical and preclinical settings, and ultimately to advance relevant diagnosis and treatments.
Funded by GSDM |
Evaluation of Genotype and Phenotype in a New Hypomaturation Type of Human Rare Dental Disease, Amelogenesis Imperfecta
Tooth enamel formation/amelogenesis is under strict genetic control that determines the composition and structure of this highly specialized tissue. Amelogenesis Imperfecta (AI) is a group of human hereditary disorders that cause abnormalities of the quantity and/or quality of enamel. Depending on the AI type, there can be significant oral morbidity. Knowledge of the molecular etiology and mechanisms leading to alteration of the structure and composition of AI enamel remains incomplete. To date, seventeen genes are associated with different forms of AI. It has been shown that the diverse AI phenotypes result from specific allelic and nonallelic genetic mutations affecting the deposition, calcification, and maturation of enamel. Our preliminary study shows that the proband exhibits markedly different hypomaturation AI phenotypes with lack of enamel mineralization contrast to dentin and a wider pulp chamber space. This clinical phenotype is different from the reported hypomaturation AI phenotypes. Therefore, I hypothesize that a new AI gene mutation in the patient family produces markedly different phenotypes through different mechanisms. There are two specific aims to test this hypothesis: 1.) evaluate phenotype and genotype in the family, and 2.) characterization of enamel in the family. This pilot, an exploratory, patient-oriented research project, will allow correlation of the phenotype-genotype of the AI, thereby allowing improved diagnoses and understanding of this difficult-to-restore/treat and devastating disease, as well as provide new knowledge of enamel formation critical for efforts directed at improving the traditional dental treatment. (Award co-funded with the BU CTSI)
Dr. Yoshiyuki Mochida is a Clinical Associate Professor of Molecular and Cell Biology at Boston University Henry Goldman School of Dental Medicine. He is a dentist – scientist whose career has been devoted to understanding and advocacy of rare dental /craniofacial diseases. He served on several NIH-, private-foundation-, and university-funded projects investigating rare dental conditions including Dentinogenesis Imperfecta, Amelogenesis Imperfecta and Ectodermal Dysplasia. He also actively help the patient support group of the families with rare dental conditions in Massachusetts. The current MA state law does not mandate the insurance companies to cover the out-of-pocket dental treatment expense for these genetic conditions although these patients suffer from genetic diseases and the treatments are medically necessary. This CTSI Pilot Award will allow correlation of the phenotype-genotype of a potentially new type of Amelogenesis Imperfecta, thereby allowing improved diagnoses and understanding of this difficult-to-restore/treat and devastating disease, as well as provide new knowledge of tooth enamel formation critical for efforts directed at improving the traditional dental treatment.
Funded by DOM |
Characterizing Care Coordination in Pulmonary Hypertension: A Qualitative Study
Pulmonary hypertension (PH) is a complex disease of the pulmonary vasculature that often requires a multidisciplinary approach to care. Care for certain high-risk PH groups also requires timely referrals from community-based settings to PH specialty care centers (SCCs), referrals that often cross healthcare systems. While engaging specialists may increase expertise in PH management, it may also result in care fragmentation and the attendant risk of duplicative or missed tests or treatments, higher costs, and worse clinical outcomes. Indeed, we have previously shown that patients with PH often receive their diagnosis and treatment in discordant locations across healthcare systems. Effective care coordination is key to reaping the benefits of specialist expertise while mitigating harms associated with care fragmentation. Achieving this important objective in PH first requires a sound understanding of the broad range of factors that influence care coordination across multiple levels. In this qualitative study of providers and patients, we will identify local contextual factors that enable or impede care coordination at the patient, provider, and health system level. When integrated with quantitative social network science results (to be conducted in parallel), these findings will lay the groundwork for the next stage of our research, in which we will develop and test an evidence-informed intervention to improve PH care coordination among multidisciplinary teams and across healthcare systems.
Meet the Team
Dr. Kari R. Gillmeyer is an Assistant Professor of Medicine at Boston University School of Medicine. She is a pulmonary and critical care physician and health services researcher whose work focuses on improving care delivery, quality of care, and outcomes for patients living with PH. Her NIH and foundation funded research utilizes quantitative, qualitative, and mixed method approaches to investigate a wide range of topics within the field of PH, such as drivers and outcomes of guideline-discordant PH care, limitations of administrative data sources in PH research, and prevalence and effects of multisystem PH care. This body of work has identified significant gaps in our understanding of pulmonary hypertension care delivery, including how care is organized and coordinated across the U.S. Her prior research serves as the motivation for this CTSI Pilot Award.
Dr. Renda Soylemez Wiener is a Professor of Medicine at Boston University School of Medicine. She is a pulmonary and critical care physician, health services researcher, and implementation scientist. The goal of her research is to improve communication and decision- making between patients and clinicians, de-implement low value, potentially harmful practices, and implement patient-centered programs. She applies mixed methods to approach complex research questions from multiple angles and has experience conducting quantitative analyses of administrative databases, qualitative analysis, survey research, and evaluations of implementation. Her work has been highly influential; she has published 5 articles that are in the top 1% of most highly cited papers in the field of clinical medicine (per Web of Science) and has an overall h-index of 38, with over 8000 citations to her work (per Google Scholar). She brings extensive, relevant content and methodological expertise to this multidisciplinary CTSI Pilot Award.
Dr. A. Rani Elwy is an Associate Professor at the Warren Alpert Medical School of Brown University in the Department of Psychiatry and Human Behavior, and Adjunct Associate Professor of Boston University School of Public Health in the Department of Health Law,Policy, and Management. She is a renowned expert in mixed methods research, stakeholder engagement methods, and implementation science. Her work focuses on building stakeholder and leadership buy-in for national policy implementation across large integrated healthcare systems; evaluating and disseminating evidence-based complementary and integrative health therapies to treat PTSD, depression, and chronic pain; social network analysis; and implementation outcome assessment. With this expertise, she will help ensure that findings from this pilot work can directly inform the development of an intervention in the next stage of research.
Dr. Elizabeth S. Klings is an Associate Professor of Medicine and Director of the Pulmonary Hypertension Center and the Center for Excellence in Sickle Cell Disease (SCD), caring for over 500 adult and pediatric patients, at Boston University School of Medicine/Boston Medical Center. Her NIH and foundation funded research has helped to define the clinical problem of pulmonary hypertension related to sickle cell disease; she is considered an international expert on the subject. She led the American Thoracic Society sponsored Clinical Guidelines for the Diagnosis and Treatment of PH in SCD (published in the American Journal of Respiratory and Critical Care Medicine in 2014) and Workshop for Defining Clinical and Research Priorities in Sickle Cell Lung Disease (published in the Annals of ATS in 2019). Her current research interests include understanding the role of venous thromboembolism in PH of SCD and improving diagnostic and treatment strategies for patients with PH due to systemic sclerosis. She brings extensive content expertise to this multidisciplinary CTSI Pilot Award.
Dr. Seppo T. Rinne is an Assistant Professor of Medicine at Boston University School of Medicine. He is a pulmonary and critical care physician, clinical informaticist, and health services researcher with a career focused on improving the organization and delivery of care for complex respiratory diseases. Much of his work has focused on improving chronic obstructive pulmonary disease (COPD) management. He has conducted quantitative, qualitative, and mixed- methods research to understand current COPD care practices and to identify improvement opportunities to expand access and improve care quality and coordination. He has previously used positive deviance methods to explore care at high vs. low performing health systems with respect to outcomes for patients with COPD, and identified clear differences in coordinated care across sites, with poor performing sites experiencing barriers to interprofessional relationships and communication. His body of work provides a framework for this pilot work examining care coordination in PH.
This CTSI pilot grant, building on recent preliminary findings of activated receptors on hematopoietic stem cells affected by the JAK2V617F mutation, focuses on novel therapeutic approaches to reducing the burden of the malignant clone in primary myelofibrosis. This project will be the crucial first step in the pursuit of translational application of this research program.
Meet the Team
Dr. Shinobu Matsuura earned her degree as a Doctor of Veterinary Medicine (DVM) from the University of São Paulo, and her PhD from the University of Tokyo, under the guidance of Prof. Hajime Tsujimoto. As an F32 fellow, she received post-doctoral training at the University of California, San Diego, at the laboratory of Dr. Dong-Er Zhang. She joined the laboratory of Dr. Katya Ravid at Boston University as a post-doctoral fellow, joining the Faculty ranks at the Cardiovascular Section/Department of Medicine as an Instructor, and was promoted to Assistant Professor in 2021. She is supported by the SERCA K01 award from the NIH/DCM/ORIP, designed to encourage veterinarians to pursue careers as independent biomedical researchers. She was driven to a career in research by the prospect of developing lifesaving treatments for hematological malignancies. Guided by a fascination with the potential of hematopoietic stem cells, her research goal is to harness the knowledge of stem cell biology to develop impactful therapies for hematological malignancies.
Dr. Katya Ravid,
Barbara E. Corkey Professor of Medicine, and Professor of Biochemistry, Biology and Health Sciences is the founding director of the Evans Center for Interdisciplinary Biomedical Research (ECIBR) and of a university-wide Interdisciplinary Biomedical Research Office (BU IBRO). She is also the Director of the Team Science Program within BU CTSI. Through her leadership roles, she developed platforms for cross-campus interdisciplinary biomedical research- the Affinity Research Collaboratives (ARCs), with documented success at discovery, publications and grant seeking levels. Dr. Ravid is also the founder and past Scientific Director of the BU Transgenic/Knockout Core, the director of an NHLBI-funded training program in Cardiovascular Biology, and the developer and current director of an interdisciplinary Master of Science program in Biological Core Technologies. While leading university initiatives and continuing teaching responsibilities, Dr. Ravid has maintained a creative research program continuously funded by NIH, the American Heart Association (AHA) and Biotech. Her pioneering work, along with that of nearly 50 pre- and post-docs and junior faculty she has guided and mentored, led to recognized discoveries in the fields of hematopoiesis and platelet/vascular biology. With her work being recognized nationally and internationally, Dr. Ravid has been the recipient of several awards such as the prestigious Fulbright Research Scholar Award, the AHA Established Investigator Award, the University of Sidney International Scholarship Award, the Weizmann Institute Professorship Visiting Award, the Robert Dawson Evans Teaching Award and the Educator of the Year Award in Graduate Medical Sciences, among other recognitions. She has served on several national and international review panels, and chaired scientific sessions such as the Gordon Research Conference on Megakaryocyte and Platelet Cell Biology.
Impact of IgA and IgM upon Nasal Microbiota in Common Variable Immunodeficiency
Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency. Respiratory ailments are the most frequent complications of CVID, with chronic pulmonary disease developing in 30-60% and even more experiencing frequent acute respiratory infections. This project aims to establish cutting-edge approaches to study pulmonary biology in CVID and apply novel bioinformatics strategies in these patients to study complex interactions among microbes and host cells directly in the respiratory tract. This will include evaluating several ways to sample gene expression in the respiratory tract and apply cutting-edge computational approaches to analyzing the complex data derived from these approaches.
Meet the Team
Dr. Paul J. Maglione is a physician-scientist in the Pulmonary Center of Boston University School of Medicine. Dr. Maglione studies human B cell biology, particularly in how it relates to and is informed by primary immunodeficiency disorders. His research program utilizes high throughput strategies such as RNA sequencing, B cell receptor repertoire analysis, and seromics together with cell culture, immunofluorescence, and information from the patient medical record to conduct bedside-to-bench studies on immunodeficiency disorders. In addition to running a research laboratory, Dr. Maglione provides clinical care for patients with immunodeficiency disorders and has particular interest and expertise in common variable immunodeficiency (CVID) and its related complications, including chronic lung disease.
Dr. Evan W. Johnson is an Associate Professor and Associate Chief of the Division of Computational Biomedicine in the Department of Medicine at Boston University. His research team has a longstanding history of applying genetics, genomics, and metagenomics data to solve problems in precision cancer therapy, infectious diseases/host response, and addiction research. His work includes a balance between statistical methods development, algorithm optimization, software development, and clinical application. Statistical innovation in his group focuses on the development of clinically motivated tools that integrate linear modeling, Bayesian methods, factor analysis and structural equations models, Hidden Markov Models, mixture models, dynamic programming, and high-performance parallel computing. This work has resulted in widely used tools and algorithms for profiling transcription factors, preprocessing and integrating of genomic data, aligning sequencing reads, developing multi-gene biomarker signatures (ASSIGN, TBSignatureProfiler), and metagenomic profiling (PathoScope, animalcules). He has successfully applied his tools and methods in the context of pathogen detection, pathway profiling of host and microbial communities, and studying host/pathogen interactions in various contexts including human nutrition, food-borne pathogens, human respiratory diseases, vector- borne pathogen biosurveillance, and in chronic conditions such as cancer and obesity. His laboratory is committed to promote diversity and enhance the training of scientists from all over the globe, and his research includes explorations in the Black Women’s Health Study and international research in the microbiome and host transcriptomics in developing countries such as Brazil, Uganda, Zambia, and India.
Novel Urinary Acute Kidney Injury (AKI) Diagnostic for Cardiothoracic Surgery Patients
In collaboration with Dr. Niloo M. Edwards, they will assess the sensitivity and specificity of urinary nucleophosmin (NPM) and phosphorylated-NPM (p-NPM) as non-invasive markers of renal damage in BMC patients undergoing cardiac surgery at high risk for acute kidney injury (AKI)
Dr. Steven C. Borkan is an Associate Professor of Medicine and Co-Director of the MD-PhD Training Program at Boston University School of Medicine, and an attending physician in the Renal Section at Boston Medical Center. His interests include education of medical students and house staff, basic research on the cellular mechanisms of acute kidney injury (AKI), and the care of underserved patients with renal disease. Dr. Borkan is the senior author of numerous publications in the pathobiology of renal cell injury during AKI and a NIH-funded Principal Investigator. He hopes to harness insights into the pathogenesis of regulated cell death to detect and ultimately treat ischemic acute kidney injury in cardiac surgery patients at high risk for this devastating complication.
Funded by CTSI |
Allostatic Load and Physical Activity as Modulators of Racial Disparities in Neurocognitive Aging in the Framingham Heart Study Cohort
Utilizing the Framingham Heart Study Brain Aging Program dataset, the goal of the CTSI pilot grant award is to examine whether racial disparities in allostatic load, the physiological ‘wear and tear’ of the body in response to chronic stress, can account for racial disparities in neurocognitive aging between Black and White older adults and whether physical activity can attenuate these neurocognitive disparities by lowering allostatic load.
Dr. Karin Schon is a cognitive neuroscientist and Assistant Professor at the Department of Anatomy & Neurobiology. She received her Ph.D. in Psychology from Boston University in 2005 and her undergraduate degree in psychology from the University of Hamburg in Germany. She is a past recipient of a K99/R00 Pathway to Independence Award from the National Institute on Aging. Dr. Schon’s research focuses on modulators of the medial temporal hippocampal memory system, including exercise, psychosocial and physiological stress, and aging. Her most recent research examines the impact of racism burden on brain and mental health across the lifespan in Black Americans.
A Prospective Mixed Methods Study of Maternal and Child Well-being and Risk of Relapse in the First Year Postpartum
The year after delivery is a vulnerable period for maternal-infant dyads in substance use recovery. Short and long-term risks include relapse, overdose, death, family dissolution and trauma. In particular, the late postpartum period represents a critical time with high rates of pharmacotherapy discontinuation by 6 months postpartum and the highest overdose rates 7–12 months after delivery. Longitudinal supports and interventions tailored to women and children in the first year postpartum are needed to address high rates of relapse and to promote dyadic well– being. The overarching goal of the First Year Study is to track the experiences of mothers in recovery and their young children in order to identify short- and long-term risk and resiliency factors for further longitudinal study and intervention development. This pilot work will be conducted in partnership with the SOFAR (Supporting Our Families through Addiction and Recovery) Clinic, an innovative, multidisciplinary primary care program built around the needs of substance-exposed infants and their parents in recovery.
Meet the Team
Dr. Mei A. Elansary is an Assistant Professor of Pediatrics at Boston University School of Medicine. Dr. Elansary has special interests in the evaluation and treatment of children with concerns about behavior and development in the context of maternal adversity. She works as the Developmental Behavioral Pediatrician for the SOFAR (Supporting Our Families through Addiction and Recovery) Program. As an early career researcher, Dr. Elansary is interested
in interventions that mitigate the intergenerational effects of maternal post–traumatic stress on child development. Dr. Elansary received her medical degree from Yale University School of Medicine. She completed pediatrics training at the Boston Combined Residency Program and completed subspeciality training in Developmental and Behavioral Pediatrics at Boston Children’s Hospital prior to joining the faculty at Boston University.
Dr. Ruth Paris is an Associate Professor at Boston University School of Social Work and the Associate Director for Research at the BU Institute for Early Childhood Well-Being. Her program of research focuses on attachment-based interventions for vulnerable families with young children. With support from SAMHSA, DOD, NIH, HRSA and private foundations, she has developed and evaluated multiple interventions implemented in a variety of community settings focused on families experiencing high adversity, including those with substance use and mental health challenges, recent immigrants, and military service members. Dr. Paris’ current and recently completed work includes leading the evaluation of interventions targeting parents with young children affected by trauma and substance misuse. One such intervention, BRIGHT, (Building Resilience through Intervention: Growing Healthier Together) is a therapeutic parenting intervention that has been offered in various substance use treatment programs including family residential treatment and methadone clinics. Dr. Paris is currently testing BRIGHT in a pragmatic randomized controlled trial for pregnant and parenting women with SUD/OUD in a specialized prenatal clinic at Boston Medical Center. She is a graduate of Smith College (MSW) and the University of California, Berkeley (PhD). Dr. Paris maintains an independent clinical practice in Greater Boston working with individuals, couples, and families.
Biomagnetic Measurements of Animal Hearts with Novel Magnetic Sensors
Professor Bishop and Dr. Josh Javor, a postdoc in his lab, recently invented a small, low-cost, low power magnetic sensor with very high sensitivity in the range of low frequency biomagnetic fields. Together they were awarded the Pilot Grant from Boston University’s Clinical and Translational Science Institute (CTSI) to detect the magnetic fields from animal hearts. If successful, their work may lead to the development of a non-contact, radiation-free cardiac diagnostic imaging tool that can increase the confidence of cardiologists during diagnosis and in the safe discharge of patients experiencing chest pain.
Dr. David Bishop is currently the Director of CELL-MET, an NSF ERC, and Head of the Division of Materials Science and Engineering at Boston University. He is also a Professor of Physics, Professor of Mechanical Engineering, Professor of Electrical and Computer Engineering, Professor of Biomedical Engineering and Professor of Materials Science and Engineering at BU. Prior to joining BU, he was the Chief Technology Officer (CTO) and Chief Operating Officer (COO) of Lucent Technologies, Bell Labs. Dr. Bishop graduated from Syracuse University with a B.S. in Physics. He received an M.S. and Ph.D. in Physics from Cornell University. Professor Bishop has over 23,000 citations on published scientific articles, 50 issued patents, and is a member of the National Academy of Inventors and the National Academy of Engineering.
Development and In Vivo Efficacy of Small-Molecule IL-4 Inhibitors
Interleukin-4 (IL-4) is a pleiotropic cytokine and an important regulator of inflammation. When deregulated, IL-4 activity is associated with asthma, allergic inflammation, and contributes to the progression of multiple infectious diseases. The impact of uncontrolled IL-4 activity is particularly evident in asthma, a chronic inflammatory disorder of the lungs that currently impacts 25 million Americans, and is characterized by breathlessness, wheeze and a variable airflow obstruction. The current clinically-approved anti-IL-4 treatment (dupilumab, a biologic) for asthma is an antibody-based inhibitor that binds the cellular receptor, but it is limited to moderate to severe forms of the disease. Small-molecule inhibitors are attractive alternatives to biologics, but identifying effective compounds that inhibit the protein-protein interactions between cytokines and their receptors remains a nascent area of research. Recently, we identified the first IL-4 small-molecule inhibitor. The compound, called Nico-52, displayed single-digit micromolar affinity and exhibited functional disruption of type II IL-4 binding in cells. This molecule serves as a starting point to develop treatments for IL-4-mediated immunological disorders like asthma where disruption of IL-4 signaling can be clinically beneficial. Here, we propose preliminary structural optimization and in vivo evaluation of our lead compound and our improved analogs in models of allergic inflammation in mice.
Meet the Team
Dr. Arturo J. Vegas is a Peter Paul Career Development Professor at Boston University. He is appointed in the Department of Chemistry and has affiliations with the Department of Biomedical Engineering and the Materials Science and Engineering Division. He is a core faculty member of the BU Center for Molecular Discovery, the BU Nanotechnology Innovation Center, the Biological Design Center, and is Co-Director of the Translational Research in Biomaterials Training Program. He has also received a New Innovator Type 1 Diabetes Pathfinder Award from the NIH. Arturo received his BA in Biology from Cornell University and a PhD in Chemistry from Harvard University. Research in the Vegas lab focuses on developing novel tissue-targeted drug delivery systems and new therapies for immunomodulation for cancer, type 1 diabetes, and immune-mediated disorders.
Dr. Felicia Chen is an Assistant Professor of Medicine at Boston University School of Medicine and a pulmonary and critical care physician at Boston Medical Center. Her research interest is to uncover the molecular and cellular mechanisms that regulate lung development, homeostasis, and injury repair. Recently, her projects focused on the impact of vitamin A signaling in airway physiology, smooth muscle phenotype, and lung microbiota interactions. In addition to her clinical and research activities, she is active in the education of predoctoral students, medical residents, and pulmonary and critical care fellows at Boston University and Boston Medical Center. Dr. Chen earned her medical degree from Albany Medical College and completed her residency and fellowship training at Boston University School of Medicine.
Developing Tools for Early Detection and Prevention of Lead Take Home
Lead poisoning in children remains a public health issue nationwide, especially within low- /medium-wage racial/ethnic minority families in construction and environmental justice communities. Construction workers typically are exposed to lead at work and can unintentionally bring lead home to their families (known as lead take–home) exacerbating other lead issues in the home. Identifying lead home issues early is not always possible. Traditional methods include hard-to-collect blood data and time-consuming and expensive lead exposure assessment in homes. Thus, this pilot study proposes to 1) validate an accessible (easy to self- collect/store/analyze), non-invasive biomonitoring method such as XRF analysis of toenail clippings, and 2) validate a 1-page risk assessment screening to predict the potential for lead exposure in the home considering lead take-home. These tools will be tested using data and samples from 60 families of construction workers (n=150) from an ongoing study. The goal of the proposed multidisciplinary translational research pilot study is to validate tools that could be used by social workers, physicians, community groups, and researchers in identifying and addressing concerns early about lead exposure in children, as well as understanding families’ lead take-home prevention education and intervention needs. They are not meant to replace traditional methods but to ensure screening has a wider reach. Specifically, tools could be used in future surveillance efforts within vulnerable communities likely to have a high representation of lead-exposed workers. A refined toenail clippings XRF method could potentially have commercial capabilities by providing instantaneous results in clinical point-of-care testing.
Meet the Team
Dr. Diana M. Cellabos is an Assistant Professor at Boston University School of Public Health. Her life’s passion is to address health disparities by identifying environmental factors that cause disease, injury, or impairment. These factors range from emerging hazards related to new technologies, to known hazards that are transferred to vulnerable populations including workers in small businesses, minorities, and workers in developing economies. Her research aims to better understand health effects from exposure to complex mixtures to uncovering and addressing the disproportionate burden of exposure in vulnerable populations. She is motivated by interdisciplinary and collaborative research projects to understand and prevent health effects of environmental and occupational contaminants in the United States and abroad. She has expertise in the development, coordination and analysis of highly complex environmental and biological sampling techniques, including the development of new sampling methodologies.
Dr. Jennifer Greif Green is an associate professor in special education and a child clinical psychologist. Her research focuses on supporting students with emotional/behavioral disorders and bullying prevention. Within these lines of research, she studies teacher identification of students with mental health needs, racial/ethnic disparities in mental health service access, and youth bullying involvement.
Dr. Noah Buncher is a pediatrician in Primary Care Pediatrics at Boston Medical Center and Assistant Professor of pediatrics at Boston University School of Medicine. His interests are varied and include adverse childhood experiences, refugee medicine, global health, and motivational interviewing. During his residency, he was awarded an AAP CATCH Grant to help establish one of Connecticut’s only dedicated pediatric global health clinics designed to provide culturally sensitive, comprehensive care to newly arrived refugee children, help transition these children to a medical home, and connect refugee families to community resources. Dr. Buncher was a Visiting Resident Scholar with Baylor International Pediatric Aids Initiative, providing clinical care to HIV positive children, adolescents, and their families at Baylor College of Medicine Children’s Foundation – Lesotho.
Disparities in Time to Diagnosis of Ankylosing Spondylitis
The team will use analytic tools developed by Observational Health Data Sciences and Informatics (ODHSI) to study the time to diagnosis among people with ankylosing spondylitis, a condition that is often associated with 6-8 years from the onset of back/joint pain to diagnosis. They will study whether the time to diagnosis varies according to gender, race, or ethnicity. By using Boston Medical Center data in the Observational Medical Outcomes Partnership (OMOP) structure, the team will be able to expand future analyses to other datasets that use the same model.
Meet the Team
Dr. Maureen Dubreuil is a rheumatologist who specializes in spondyloarthritis. Her work focuses on comorbidities and pharmacoepidemiology of spondyloarthritis.
Dr. S. Reza Jafarzadeh is an epidemiologist with a research interest on the application of causal inference methods in observational studies of rheumatic diseases using OHDSI tools and data standards.
Gut health, Micronutrient Status, and Linear Growth Among Infants in Lusaka, Zambia
Undernutrition during the critical window from conception until 2 years increases the risk of mortality. Among the children who survive, it can have lifelong effects on the immune, metabolic and central nervous systems. Globally, 149 million children <5 years are stunted (length/height-for-age z-score [LAZ/HAZ] <-2SD of WHO median), often due to chronic undernutrition. The global COVID-19 pandemic has substantially increased food insecurity and malnutrition, particularly in low- and middle-income countries (LMICs) like Zambia, where 40% of children <5 years were stunted as of 2018. Interventions and research targeting stunting have historically focused on nutrient intake and clinical infections; however, nutrient malabsorption, resulting from poor intestinal health, may also drive stunting even in the context of adequate intake. Gaining a better understanding of the role of intestinal health in child growth will help inform the design of more effective interventions. This study will analyze biospecimens collected during the baseline assessment from a randomized controlled trial (RCT) that will assess the impact of lipid nutrient supplements (LNS) on stunting in Zambia. CTSI funds will support the analysis of serum specimens for biomarkers of environmental enteric dysfunction (EED) and 16S sequencing of rectal swabs to describe the gut microbiome in the infants. Their primary aims are to evaluate the association between biomarkers of EED and the GI microbiome with infant stunting in Zambia.
Meet the Team
Dr. Lindsey M. Locks is an Assistant Professor in the Departments of Health Sciences (Sargent College) and Global Health (School of Public Health). She directs the Sargent College Global Nutrition Lab, and her research focuses on undernutrition in women and children in low- and middle-income countries. Her current research focuses on the role of human milk, micronutrients, infant and young child feeding practices in infant gut health and pediatric growth. She has 15 years of experience in global nutrition research and programs in sub-Saharan Africa and South Asia. She holds a ScD in Nutritional Epidemiology from the Harvard Chan School of Public Health and a MPH in Epidemiology and Global Health from the Columbia University Mailman School of Public Health.
Dr. Peter Rockers is an Associate Professor in the Department of Global Health at the Boston University School of Public Health. He is the Director of the Global Health Program Design, Monitoring & Evaluation certificate within the MPH program. Dr. Rockers’ research is primarily concerned with understanding and improving child development outcomes in low- and middle- income countries. He uses epidemiologic methods to investigate biological and social determinants of child development. He also uses experimental methods to test the impacts of interventions that aim to improve child development. Dr. Rockers is particularly interested in the relationship between poverty and neurodevelopment
Dr. Jacqueline M. Lauer is a Clinical Assistant Professor in the Department of Health Sciences at Boston University. Her research focuses on the environmental contributors to poor growth and development among infants and young children in low-resource settings. She completed a postdoctoral research fellowship at Boston Children’s Hospital where she studied the causes, consequences, and assessment of environmental enteric dysfunction (EED), a subclinical, inflammatory disorder of the small intestine. She completed her PhD in Food Policy and Applied Nutrition from Tufts University’s Friedman School of Nutrition Science and Policy while working as a researcher for USAID’s Feed the Future Innovation Lab for Nutrition in Uganda. She also holds a MPH in International Health and Development and a BSPH from Tulane University.
Impact of APOL1 Renal Risk Variants on Placental Function and Racial Disparities in Preeclampsia Risk
Compared with whites, black pregnant people have a 1.7-fold increased risk of preeclampsia (PE) and are three times more likely to die of PE. They hypothesize that variants in the apolipoprotein L1 (APOL1) gene, a strong risk factor for kidney disease in black individuals, impact the development of the placenta and predispose black birthing people to an increased risk of PE. Epidemiological studies have shown the fetal/placental APOL1 genotype to be associated with increased PE risk. The goal of this proposal is to elucidate the effects of APOL1 variants on placental invasion and function by 1) defining the expression patterns of APOL1 in placental compartments over gestation, and 2) assessing the effect of APOL1 variants on trophoblast function through gene overexpression studies in trophoblast cell lines. Ultimately, delineating the impact of APOL1 variants on placental development may provide new insights into the complex pathophysiology of PE among black pregnant people and may identify novel therapeutic targets.
Meet the Team
Dr. Wendy Kuohung is the Division Director of Reproductive Endocrinology and Infertility at Boston Medical Center and an Associate Professor of Obstetrics and Gynecology at Boston University School of Medicine. Dr. Kuohung received her medical degree from the Yale University School of Medicine. She completed her Obstetrics and Gynecology residency training at Boston Medical Center and fellowship training in Reproductive Endocrinology and Infertility at Brigham and Women’s Hospital. Dr. Kuohung’s research interests are focused on placental development, infections of the reproductive tract, and reproductive health care disparities. She also has clinical expertise in advanced minimally invasive and robotic gynecologic surgery, female infertility, and fertility preservation. Dr. Kuohung was a former Reproductive Scientist Development Program Scholar and has served as PI on a number of NIH and pharmaceutical research grants since 2003.
Dr. Nader Rahimi is a molecular biologist and currently an Associate Professor at the Department of Pathology and Laboratory Medicine at Boston University. Nader Rahimi has extensively published in the field of signal transduction by receptor tyrosine kinases in particular VEGF receptor tyrosine kinases. His notable works include the demonstration of the differential function of VEGFR-1 and VEGFR-2 in angiogenesis, identification of lysine methylation as a novel mechanism of activation of VEGFR-2, and establishing protein ubiquitination as a major pathway modulating the angiogenic signaling of VEGFR-2. He is also responsible for the discovery of multiple cell surface receptors including, IGPR-1 (TMIGD2), TMIGD1, MINAR1, and MINAR2. His recent work on COVID-19 resulted in the discovery of CD209L and CD209 as novel receptors and vimentin as an attachment factor for SARS-CoV-2.
Improve Language Diversity in Clinical Trials
Even though many patients with limited English proficiency (LEP) can be helped through clinical trials, they are often excluded due to a lack of diverse research teams that are able to effectively engage with them. This gap in trial representation translates to a gap in treatment. Boston University School of Social Work (BUSSW) Dr. Martinez will help close this gap by testing and assessing promising engagement strategies with a grant from the Boston University Clinical and Translational Science Institute (CTSI). The CTSI Integrated Pilot Grant Program has awarded funds to study CTSI sites including Boston Medical Center, where 31% of patients report a first language other than English.
Advancing language justice in clinical trials requires an investment in systems-level change to support the intentional inclusion of LEP patients. “The enrollment and retention of LEP patients in research requires diverse research teams who are able to communicate, engage, and build trust with limited-English speaking populations,” Sprague Martinez explains. “Solutions that lead to fully representing LEP patients in research may provide increased access to specialized novel treatments only available through trials, and thus serve to bridge racial and ethnic disparities in health.” These steps will create a collection of best practices for medical institutions to adopt.
Meet the Team
Linda Sprague Martinez is associate professor and chair of the Macro Department at the Boston University School of Social Work. She is interested in examining asset-based strategies to tackle health inequities as such community-engaged research (CEnR) approaches like community-based participatory research (CBPR) and youth-led participatory action research (YPAR) are central to her work. Having formerly worked in municipal and state governance, and as an adolescent mental health provider, she brings practical expertise in community collaborations designed to engage diverse communities of color and low-income residents in community planning and intervention development. In 2017 she was a Boston Housing Authority, Center for Community Engagement and Civil Rights, Resident Empowerment Coalition, Resident Empowerment Honoree.
James Feldman, MD
A member of the research faculty in the Department of Emergency Medicine.Chair of the Boston Medical Center/Boston University Medical Campus IRB Panel Blue and Professor of Emergency Medicine at the Boston University School of Medicine and Director Regulatory Quality and Efficiency BU-CTSI. Research interests have included prehospital emergency medical care, acute cardiac ischemia, cocaine induced cardiac ischemia, public health and human subjects research ethics. Served as President of the Massachusetts College of Emergency Physicians (MACEP) 2008-9. The recipient of several teaching and academic awards including the Pinnacle Award from MACEP (2012), the Mark E. Weinstein MD award for contributions to regional emergency medical services (2012) and the Grant V. Rodkey MD award from the Massachusetts Medical Society (MMS), 2014.
Tracy Battaglia is an Associate Professor of Medicine and Epidemiology at Boston University Schools of Medicine and Public Health where she serves as the Director of the Women’s Health Unit, a DHHS designated Center of Excellence in Women’s Health. A graduate of Boston University School of Medicine, Public Health and the GIM Fellowship program (2001), she has been a faculty at BUSM since 2001. As a practicing internist and breast health specialist at Boston Medical Center, the largest safety-net medical center in New England, her approach to health disparities focuses largely on engaging the community as partners in the research process. A pioneer in the development of oncology Patient Navigation programs that target under-resourced cancer patients, Dr. Battaglia has contributed to the scientific evidence solidifying the impact of navigation on reducing delays across the continuum of cancer care. She is currently leading a cooperative study funded by the National Center to Advance Translational Science (NCATS) in partnership with the four Massachusetts Clinical and Translational Science Award (CTSA) hubs (Boston University, Harvard University, Tufts University, and the University of Massachusetts) to support a City-wide dissemination study to reduce breast cancer disparities through a patient navigation network.
Rebecca Lobb is the Assistant Director of Community Engagement (CE) for Boston University’s Clinical and Translational Research Institute. She has extensive experience in community-engaged research collaborations with community-based organizations, public health departments, health care organizations, and resident groups to develop sustainable cancer control programs for vulnerable populations
Chris Sheldrick, PhD
Dr. Chris Sheldrick’s research focuses on the science and practice of screening and clinical decision making, spanning from instrument development to implementation and evaluation of screening protocols. Collaborating with Dr. Ellen Perrin, Dr. Sheldrick helped to create the Survey of Wellbeing of Young Children (www.theSWYC.org), a freely available comprehensive screening instrument for young children. Together, they are now completing a study comparing the accuracy of several developmental and behavioral screening instruments that are prominently used in pediatrics. In addition, Dr. Sheldrick has received training in systems science and decision analysis through a KM1 fellowship. Dr. Sheldrick’s current research applies these methods with the goal of helping clinicians improve identify and help children with developmental and behavioral problems in a range of community settings.
Ryan Schroeder
Director, Clinical Research Network at Boston Medical Center (BMC
Over 20 years serving in functional and technical leadership roles in sponsored research administration and clinical research operations at universities and research hospitals. Ryan has led industry sponsored research at UCSF, Cedars-Sinai Medical Center and a California-based community health system, specializing in building high performing, community engaged research programs. Ryan serves as the director of BMC’s Clinical Research Network; an innovative unit started in 2021 that merges community engaged values, removing infrastructural barriers to inclusive research participation, and highly experienced research staffing to manage BMC’s most important health equity-based clinical trials.
Senior Director at Boston Medical Center (BMC), Department of Research Administration.
Jennifer Pamphile is the Community Engagement Specialist for the Community Engagement Program of Boston University’s Clinical and Translational Research Institute. Jennifer has several years of experience in supporting various stakeholders through capacity building and enhancing participatory research knowledge. Previously she worked with the Women’s Health Unit as a bilingual research assistant and community engagement coordinator. Her past work has culminated in the co-creation of public-facing training programs that introduce the audience to Community Engaged Research while improving advocacy, storytelling, and empathic communication skills. She returns to our team from a publishing company where she supported large scale academic- industry collaborations centered around data science. Jennifer received her Bachelor’s of Science in Behavioral Neuroscience and her Master’s of Public Health in Urban Health from Northeastern University.
Riana Howard, MSW (Doctoral RA)
Riana Howard is a first-year doctoral student with an interest in researching how the incorporation of trauma-informed practices into education systems can improve the mental health of marginalized youth and decrease the trauma caused through the education process. She is also interested in researching school discipline practices amongst students of color, carceral logic, and their connection to the school-to-prison pipeline. She earned her MSW degree from California State University, Monterey Bay in 2015. Since graduating, she has been employed in higher education working with non-traditional students (transfer students, student parents, former foster youth students, and formerly incarcerated students), supporting student equity programs, working with Hispanic Serving Institute (HSI) grants, and the African American Resource and Cultural Center. Her work is rooted in educational equity practices and assisting in breaking down systematic barriers in the educational system.
Cristina Araujo Brinkerhoff, MA (Doctoral RA)
Cristina Brinkerhoff is currently a doctoral candidate with interests in immigrant health disparities, social networks, social support, mental health, immigration policies, and community-based participatory research. Before joining BU as a doctoral student, Cristina worked at the Institute for Community Health as a Research Associate. She also worked as an NIH Research Fellow at BU and UMass Boston on an exploratory study about the implication of transnationalism, culture, and social networks for the health and behavior of Brazilian and Dominican immigrants. She is also currently secretary of the Brazilian Workers Center board. Cristina graduated from UMass Boston with a BA in Sociology in 2011 and a MA in Applied Sociology in 2014.
Inverse Spectroscopic Optical Coherence Tomography for the Detection of Corneal Ultra-Structural Changes in keratoconus and Quantification of Corneal Cross-linking
Keratoconus is a progressive condition characterized by thinning and steepening of the corneas, leading to significant vision loss generally by the 2nd to 3rd decade of life. Corneal cross-linking (CXL) is a surgical treatment used to stiffen the cornea to prevent further progression, and results in the cross-linking of collagen fibrils and increased collagen fiber diameter. Despite the advent of CXL for this previously inexorable disease, primary clinical challenges include the inability to immediately evaluate the efficacy of CXL, which fails up to 20% of the time, as well as selecting appropriate CXL candidates prior to additional disease progression. They propose to address these challenges by using a novel imaging method, inverse spectroscopic optical coherence tomography (ISOCT), to detect and quantify corneal ultra-structural changes after CXL, as well as to detect native ultra-structural differences in keratoconus. The advantages of ISOCT are its super sensitivity to nanoscopic tissue changes achieved through spectral sensing, its rapid imaging speed (~4s per scan), and its ability to create a 3D map over a large field of view (~5x5x2 mm3). ISOCT can measure collagen cross-linking in vitro, and preliminary data suggests ISOCT can detect changes one month after CXL in keratoconus patient eyes, as well as between normal and keratoconus corneas. Their specific aims are to validate that ISOCT can quantify CXL-associated changes in vivo, including immediately after treatment, and also determine whether ISOCT markers correlate with increasing severity or instability of keratoconus. ISOCT has the potential to be a valuable new clinical tool.
Meet the Team
Dr. Hyunjoo Lee is a board-certified ophthalmologist, with fellowship training in cornea, external disease and refractive surgery. As a current attending ophthalmologist at Boston Medical Center and Boston University Eye Associates, and the director of the cornea service, she cares for patients with a variety of corneal and ocular surface conditions, including many patients with keratoconus, a progressive disease of the cornea that can lead to profound vision loss. She is an experienced corneal surgeon, performing corneal cross-linking to treat keratoconus, laser vision correction, cataract surgery, and all types of corneal transplantation.
Dr. Lee has been actively involved in clinical and translational research, including as a lead co- investigator in a randomized, double-masked, clinical trial to compare oral sedation to intravenous sedation for ocular procedures, and is the site PI for multiple clinical trials. She holds numerous approved IRB applications, including for the study of using novel optical coherence tomography techniques for imaging the cornea and ocular surface. A significant focus of her research has been in imaging modalities that can aid in the diagnosis of corneal and ocular surface conditions. She has presented work on imaging of ocular surface squamous neoplasia and keratoconus at multiple Association for Research in Vision and Ophthalmology (ARVO) meetings. She has received both an NIH CTSI pilot grant through Boston University School of Medicine as the principal investigator (PI), and an NIH R21 grant as a co-PI for studying the application of inverse-spectroscopic optical coherence tomography and two-photon autofluorescence imaging to the differential diagnosis of ocular mucosal pathologies, in collaboration with bio-engineer Dr. Ji Yi of the Department of Bioengineering at Johns Hopkins University, which has led to the publication of their novel findings. Dr. Lee and Dr. Yi are now pursuing the application of this novel imaging technology to the diagnosis and treatment of keratoconus.
Dr. Ji Yi is an Assistant Professor of Medicine at BU School of Medicine. He completed his undergraduate and PhD degrees in biomedical engineering at Tsinghua University in 2005 and Northwestern University in 2012, respectively. He started independent research at Boston University in 2015 and transitioned to Johns Hopkins University’s Department of Biomedical Engineering and Ophthalmology in 2020. He specializes in optical imaging, in particular developing multimodal volumetric microscopy across large length scales of biological systems. His PhD research is focused on early gastroenterology (GI) cancer detection using light scattering; he started ophthalmic imaging in his postdoc training. He has made several impactful technical innovations including inverse spectroscopic optical coherence tomography, visible light OCT, and oblique scanning laser ophthalmoscopy. He has contributed over 60 peer-reviewed journal articles, and is the co-inventor on 6 US and international patents. He is leading and participating in several NIH-funded studies. He has received numerous early career awards including Baxter Young Investigator Award (2013), JDRF Postdoctoral Fellowship (2014), BrightFocus Foundation awards (glaucoma national award in 2017, macular degeneration award in 2018), Boston University KL2 Career Development Award (2017) and Boston University Evans Junior Faculty Research Merit Award (2018).
Modeling Developmental Alterations Linked to Congenital Hydrocephalus Using Zebrafish
Congenital hydrocephalus is a frequent neurodevelopmental disorder (~1:1,000 births) caused by alterations in the function of the brain ventricular system. It is a major cause of child mortality and morbidity, representing up to 3% of all pediatric hospital charges. The standard treatment for congenital hydrocephalus, shunt implantation, has been the same for over 60 years and remains associated with a high risk of failure. Sequencing efforts have revealed genetic mutations in patients with inherited congenital hydrocephalus, but the mechanisms by which dysfunctions of these genes affect development and function of the brain ventricular system remain largely unknown. They propose to generate a collection of zebrafish mutant lines carrying mutations in genes linked to congenital hydrocephalus to define the developmental defects in the brain ventricular system associated with the disease. Zebrafish embryos are optically clear; it allows the direct visualization of the entire development of the brain ventricular system, which is not possible in other vertebrate organisms. They anticipate that this collection of zebrafish mutant lines will serve as a valuable resource to define the biology underlying congenital hydrocephalus and find new cures.
Dr. Arthur Marivin is a Research Assistant Professor in the Department of Biochemistry at Boston University School of Medicine. He received his Ph.D. at the University of Burgundy in Dijon, France. Dr. Marivin’s research focuses on characterizing novel principles of G-protein signaling and defining their role in disease. His previous work as a postdoc in the Garcia-Marcos lab (Department of Biochemistry) uncovered how alterations in G-protein signaling networks cause cancer or birth defects that include congenital hydrocephalus. His research combines dissection of signaling circuits using in vitro biochemistry and synthetic biology tools with disease modeling in vivo using Xenopus and zebrafish embryos.
Multiomic Phenotyping in Cardiac and Skeletal Muscle in Heart Failure with Preserved Ejection Fraction
Heart failure with preserved ejection fraction (HFpEF) is the result of a complex interplay of multiple comorbidities. Mitochondrial dysfunction and metabolic disturbances are present in both myocardial and skeletal muscle beds in models of HFpEF. However, the omics approaches for identifying unique signatures in HFpEF have predominantly targeted circulating blood or single-chamber biopsy sites and are performed in isolation, inadequately capturing the opportunity to deeply characterize tissue relevant to HFpEF pathogenesis to identify novel pathways for targeted interventions. To address these gaps, we propose to leverage an active collaboration with cardiac pathologists and a well-established rapid autopsy pathology program, to characterize the cardiac and skeletal muscle phenotype of individuals with and without HFpEF. This BU CTSI proposal is aimed at utilizing multiomics of cardiac and skeletal muscle tissue in human HFpEF to evaluate the relations of the molecular interactome across tissues and to identify novel therapeutic targets and interventions. This application leverages existing multidisciplinary collaborations to fund preliminary data to strengthen a multi-PI R01 grant submission.
Dr. Deepa M. Gopal
Assistant Professor of Medicine, Cardiovascular Division
She is a clinician-investigator whose research focuses on developing a phenotyping strategy to identify early heart failure (HF) with preserved ejection fraction (HFpEF) in individuals with obesity. This strategy will help direct mechanistically-driven therapeutics earlier in an individual’s HF disease trajectory to mitigate risk. This research harnesses her clinical expertise using novel cardiac deformation imaging in echocardiography, invasive and non-invasive cardiopulmonary exercise testing, and circulating/tissue biomarkers as key components of her methodology.
Dr. Jessica L. Fetterman
Assistant Professor of Medicine in the Whitaker Cardiovascular Institute
She is a basic and translational scientist in cardiovascular pathophysiology. Her research program utilizes trans-disciplinary approaches to advance their understanding of the role and mechanisms of mitochondrial genetics in cardiovascular pathophysiology. To do so, they evaluate mitochondrial genetics and biology at the population level through genetic epidemiology and systems biology approaches, at the cardiovascular tissue level through rapid autopsy samples and biopsies, and through the creation of cardiovascular cells from human induced pluripotent stem cells. They are creating a number of software packages aimed at enhancing their ability to delineate pathogenic and benign mitochondrial genetic variants and to enable the investigation of mitochondrial-nuclear genetic interactions. Their goal is to identify the mechanisms for how mitochondrial genetic variation contributes to the development of cardiovascular diseases.
Soft Micro Robotic Needle Steering Mechanisms for Interventional Bronchoscopy
Lung cancer remains the leading cause of death from cancer in the U.S. Early diagnosis is
of paramount importance to increase the survival rate of lung cancer and can only be achieved via accurate tissue sampling. This is particularly challenging while navigating in the deep locations of the lungs, where the angles of the various takeoffs of the bronchi can be difficult to access and cancer can remain undetected. Robotic platforms for interventional bronchoscopy, currently available on the market, lack distal dexterity and the capability to achieve sharp turns. This pilot grant will focus on novel robotic actuation mechanisms to steer the tip of biopsy tools and enable tissue sampling in difficult to reach areas of the lung.
Meet the Team
Dr. Sheila Russo is an Assistant Professor in the Department of Mechanical Engineering and the Division of Materials Science and Engineering at Boston University. She completed her Ph.D. degree at the BioRobotics Institute, Sant’Anna School of Advanced Studies (Italy) and her postdoctoral training at the Harvard John A. Paulson School of Engineering and Applied Sciences and the Wyss Institute for Biologically Inspired Engineering. She is the founder and director of the Material Robotics Laboratory at BU that focuses on design, mechanics, and manufacturing of novel multi-scale and multi-material biomedical robotic systems. Her research interests include medical and surgical robotics, soft robotics, sensing and actuation, meso- and micro-scale manufacturing techniques, and advanced materials.
Dr. Ehab Billatos is an Assistant Professor of Medicine at Boston University Medical Center specializing in pulmonary and critical care. He serves as the Director of Inpatient Pulmonary Clinical Services, the Director of the Pleural Disease Service, and the Assistant Director of Bronchoscopy at Boston University Medical Center. He has a special interest in advanced bronchoscopic techniques for diagnosis of lung cancer. He also serves as the Principal Investigator for the DECAMP consortium (Detection of Early Cancer Among Military Personnel) which aims to improve the early diagnosis of lung cancer via biomarker validation and development from minimally invasive specimens. This is a multi-center trial sponsored by the Department of Defense, the National Cancer Institute, Johnson & Johnson, and NovartisPharmaceuticals.
2021 Integrated Pilot Grant Awardees
A Patient-Specific Induced Pluripotent Stem Cell (iPSC)-based Organoid Model of Pulmonary Fibrosis
The incompletely understood pathogenesis of pulmonary fibrosis and lack of reliable preclinical disease models have been major hurdles in developing effective therapies. Emerging literature now implicates alveolar type 2 (AT2) cell dysfunction as an initiating pathogenic event in the onset of a variety of pulmonary fibrosis syndromes, including adult idiopathic pulmonary fibrosis (IPF) and childhood interstitial lung disease (chILD). However, the inability to access primary AT2 cells from patients, particularly at early disease stages, has impeded the identification of disease-initiating mechanisms. The goal of this proposal is to provide a patient-specific in vitro model system, based on induced pluripotent stem cell-derived AT2 cells that we have engineered in vitro from patients with pulmonary fibrosis associated with the most common disease-associated SFTPC variant (SFTPCI73T), in order to uncover the mechanisms leading to human AT2 cell dysfunction, at the moment of disease inception.
Dr. Konstantinos-Dionysios Alysandratos obtained his medical degree and doctoral degree in Immunopharmacology from the University of Athens in Greece. He completed his internal medicine residency training at the University of Texas Southwestern and Parkland Medical Center in Dallas, TX. Followingly, he pursued clinical fellowships in Sleep Medicine and Pulmonary/Critical Care Medicine at Boston University Medical School and Boston Medical Center. During his fellowship training, he joined Dr. Darrell Kotton’s laboratory at the Center for Regenerative Medicine (CReM) of Boston University and Boston Medical Center. He is currently an Assistant Professor of Medicine at Boston University School of Medicine.
His current research aims to expand our scant knowledge of the pathogenesis of common lung diseases such as interstitial lung disease (ILD) and specifically the role of alveolar type 2 (AT2) cells at the inception of disease. Under the mentorship of Dr. Darrell Kotton, he has developed an in vitro model system that permits investigation of epithelial-intrinsic events that lead to AT2 cell dysfunction over time using patient-derived cells that carry a disease-associated variant, SFTPCI73T, known to be expressed exclusively in AT2 cells.
Dr. Alysandratos has received several honors and awards throughout his career including from the American Thoracic Society and the American Lung Association. While in residency training, he was voted as an honorary member of the Alpha Omega Alpha Medical Honor Society by the university’s academic community. Most recently, Dr. Alysandratos received the Pulmonary Fibrosis Foundation I.M. Rosenzweig Junior Investigator Award for his innovative research on stem cell-based models of pulmonary fibrosis.
Culturally-Adapted Motivational Interviewing and Contingency Management for Reducing Illicit Stimulant Use in Black and Latin People
This CTSI pilot study is preliminary work in attempting to combine three approaches to treating stimulant use disorder in Black and Latinx people: 1) culturally adapted motivational interviewing; 2) recovery coaching; and 3) contingency management. We will first conduct focus groups in Black and Latinx people who use stimulants, in order to inform the adaptation of an existing motivational interviewing intervention. We will then pilot test this adapted intervention, which will be delivered by recovery coaches, in a clinic that provides contingency management treatment for stimulant use.
Meet the Team
Dr. Tae Woo (Ted) Park is an Assistant Professor of Psychiatry at Boston University School of Medicine. He is an addiction psychiatrist and researcher. He has a NIDA K23 award that aims to reduce benzodiazepine use in patients who receive opioid agonist treatment. His clinical focus is on the treatment of addiction and its psychiatric comorbidities. He is the medical director of the ABOVE program at Boston Medical Center, a program that focuses on treating co-occurring opioid use and mental disorders, and a consultant for BMC’s CATALYST program for transitional age youth with substance use disorders. In addition, he is active in the education of residents and addiction psychiatry fellows at Boston University/Boston Medical Center. He completed his psychiatry training at Western Psychiatric Institute and Clinic in Pittsburgh, PA, and his postdoctoral research at the Boston VA and Boston University School of Medicine.
Dr. Ricardo Cruz is a primary care physician at Boston Medical Center in the Department of Medicine, Section of General Internal Medicine. He is a graduate of Boston University School of Medicine (BUSM) and the BUSM/Boston Medical Center (BMC) Internal Medicine Residency Primary Care Training Program. He is the Principal Investigator of the Department of Health and Human Services Office of Minority Health funded Project RECOVER (Referral, Engagement, Coaching, Overdose preVention Education in Recovery), a project that utilizes peer recovery coaches to assist with engagement and retention of individuals with opioid use disorder into treatment and primary care services after completion of acute treatment services (detoxification). In addition, he is a Clinician Educator and is part of the Core Faculty of the Internal Medicine Primary Care Training Program at BUSM/BMC. He is in the BUSM Academy of Medical Educators where he teaches medical students during the pre-clinical doctoring courses with a focus on the development of clinical reasoning. He has been a co-investigator on NIAAA and NIDA-funded randomized clinical trials testing medications for alcohol and cocaine use disorders. His interests are in providing primary care and treatment for substance use disorders for vulnerable populations including racial and ethnic minority communities and individuals with a history of criminal justice involvement.
Dr. Christina S. Lee is an associate professor in the School of Social Work at Boston University (BUSSW) and a faculty affiliate at BU’s Center for Antiracist Research. Her research bridges the areas of intervention science, addiction psychology, and health disparities. By focusing on the effects of social and environmental stressors, Dr. Lee has become an influential voice in efforts to reduce risky health behaviors among diverse, understudied groups. She is PI and co-PI on NIH-funded addiction treatment research, affiliate training faculty at the Center for Alcohol and Addiction Studies at Brown University, research core director at the BUSSW Center for Innovation in Social Work and Health, and mentors graduate and postdoctoral scholars from diverse racial-ethnic groups. Dr. Lee is a member of the editorial board of the Journal of Consulting and Clinical Psychology.
Epidemiology COVID-19 Response Corps
In response to the COVID-19 pandemic, Drs. Ellie Murray and Jennifer Weuve created the Epidemiology COVID-19 Response Corps (or COVID Corps for short), which brought together over 150 students, faculty, and alumni to help fill gaps in COVID research and develop messaging tools to help people understand how to stay safe. Our CTSI funded project will conduct an impact evaluation of the COVID Corps so that we can understand what worked well, what didn’t work as well, and what we can do better going forward during this pandemic and in future public health crises.
Dr. Eleanor J. Murray is an Assistant Professor of Epidemiology at Boston University School of Public Health who focuses on improving methods for evidence-based decision-making and human-data interaction. Her work primarily focuses on applications to public health and clinical epidemiology, including applications to HIV, HPV, cancer, cardiovascular disease, psychiatric disorders, musculoskeletal disorders, social and environmental epidemiology, and maternal and adolescent health. Dr. Murray also conducts meta-research evaluating bias in existing research. During the COVID pandemic, Dr. Murray has been working on improving science communication about epidemiology and public health concepts and identifying and addressing barriers to equitable vaccination distribution and acceptance. She completed a postdoctoral research fellowship in Epidemiology at the Harvard T.H. Chan School of Public Health, working on causal inference for comparative effectiveness and real-world evidence in the HSPH Program on Causal Inference. She holds a ScD in Epidemiology and a MSc in Biostatistics from Harvard, an MPH in Epidemiology from Columbia Mailman School of Public Health, and a BSc in Biology from McGill University. Dr. Murray is an Associate Editor for Social Media at the American Journal of Epidemiology and can be reached on Twitter at @EpiEllie
Dr. Jennifer Weuve is an associate professor of epidemiology at the Boston University School of Public Health. In her research, she seeks to identify causes of cognitive decline and dementia, particularly environmental causes. Undergirding this research is her dedication to aligning epidemiologic methods to solving public health problems. She is the PI or co-investigator of several NIH-supported investigations and projects in all of these realms. During the COVID-19 pandemic and with Dr. Ellie Murray, she co-founded the BUSPH Epidemiology COVID-19 Response Corps, which engages with students, faculty, and other BU community members to address important epidemiologic issues related to the COVID-19 pandemic, including research, communication, policy, and best practices. Dr. Weuve earned her master’s in public health degree from the University of Minnesota and her doctoral degree from the Harvard TH Chan School of Public Health.
Generation of a Conditional Mouse Strain for GNB2 to Investigate Legionellosis
In the current CTSI pilot grant, Dr. Bosmann and his co-workers aim to generate a novel floxed mouse strain for tissue-specific gene deletion of the G-protein subunit, GNB2. The conditional knockout mice will later be used to study the role of GNB2 in myeloid cells during Legionella infection of the lung.
Dr. Markus Bosmann is an Associate Professor in the Pulmonary Center, Department of Medicine holding secondary appointments in the Department of Pathology & Laboratory Medicine, BUSM, and the National Emerging Infectious Diseases Laboratories (NEIDL). He graduated as a Doctor of Medicine, with a summa cum laude honor thesis, from the Johann Wolfgang Goethe University, Frankfurt, Germany. He continued his career with residency training in medicine, laboratory medicine, and a research postdoctoral fellowship at the University of Michigan, Ann Arbor, followed by a junior faculty appointment at the Johannes Gutenberg University, Mainz, Germany. His research interests are focused on the cellular and molecular pathogenesis of infection-associated inflammation. The work in his multidisciplinary, diverse research team is centered around understanding the host response to microbial pathogens in the context of lung injury, pneumonia, and sepsis. Dr. Bosmann is also the director of the newly established Affinity Research Collaborative (ARC) named Respiratory Viruses: A Focus on COVID-19. He was awarded the Hugo-Schottmüller prize of the German Sepsis Society in 2020.
HIV-1 RNA Modification as a Driver of Innate Immune Activation
HIV-1+ individuals on successful anti-retroviral therapy still suffer from various complications caused by chronic inflammation, but the mechanism underlying persistent inflammation is currently unclear. We have shown that expression of HIV intron-containing RNA (icRNA) in infected macrophages induces pro-inflammatory responses, however, what makes HIV icRNA immunostimulatory remains unclear. Epitranscriptional modifications in viral RNAs have been linked to various biological processes including innate immune sensing and induction of type I interferon and pro-inflammatory responses. We, therefore, hypothesize that HIV icRNAs are marked by unique base modifications, which confers immune-stimulatory capacity to HIV icRNA. To test this hypothesis, in collaboration with Dr. Daniel Cifuentes, Assistant Professor in the Department of Biochemistry, we will use two complementary approaches to quantify RNA modifications in HIV icRNA: 2D thin-layer chromatography (TLC) and nanopore sequencing (Oxford Nanopore Technologies). We will determine the quantity and position of RNA modifications in HIV icRNAs. We hope that the successful completion of this proposal will serve as a basis for a future NIH R01 grant that will focus on the roles of HIV RNA modification in innate immune responses. Ultimately, identification of HIV RNA modifications responsible for immune activation could lead to the development of novel therapeutic strategies to manage inflammation-associated complications in HIV+ individuals on anti-retroviral therapy.
Meet the Team
Dr. Hisashi Akiyama received his Ph.D. from Kyoto University, Japan. He performed his postdoctoral research at the University of Heidelberg in Germany where he worked on cellular and molecular mechanisms of HIV replication. He is currently a Research Assistant Professor in the Department of Microbiology at Boston University School of Medicine. His research goal is to understand the pathogenesis of HIV. In particular, he is interested in the role of myeloid cells in the establishment and dissemination of HIV infection and mechanisms of virus evasion from innate and adaptive host immune responses.
Dr. Daniel Cifuentes is an Assistant Professor in the Department of Biochemistry at the Boston University School of Medicine. Dr. Cifuentes received his Ph.D. from the University of Barcelona, Spain, for his studies in metabolic regulation. He completed his postdoctoral training in the Department of Genetics at Yale University School of Medicine, where he specialized in microRNA biology and vertebrate embryogenesis. His research goals at Boston University combine high-throughput genetic, genomic, and proteomic approaches to address fundamental questions of RNA regulation in viral and vertebrate systems.
Highly Multiplexed Immunophenotyping of Aggressive Histologic Patterns of Early-Stage Lung Adenocarcinomas
Lung cancer remains the leading cause of cancer death, in large part due to our inability to intercept the disease process prior to progression to an advanced and lethal state. We lack an understanding of the earliest targetable molecular events in lung carcinogenesis and effective strategies to identify and treat aggressive cancers. Using single-cell proteomics, via imaging mass cytometry (IMC) we will study immune cell marker expression and localization in normal tissue and adjacent LUAD with either aggressive or indolent histologic patterns that may identify biomarkers to predict the presence of aggressive cancers. The proposed study leverages a unique set of early-stage LUAD tumors with extensive pathologic characterization that may start to unravel aggressive LUAD immune changes, which has implications for lung cancer diagnosis and interception. The results of this work may suggest new lung cancer interception strategies for early-stage invasive LUAD as well as improve current clinical management and outcomes. Our findings will serve as pilot data for a planned NIH R01 proposal.
Meet the Team
Dr. Sarah A. Mazzilli is an Assistant Professor of Medicine at Boston University School of Medicine in the section of Computational Biomedicine. Sarah earned her Ph.D. in Molecular Pharmacology & Therapeutics at Roswell Park Comprehensive Cancer Center (SUNY Buffalo followed by a postdoctoral fellowship at Boston University with Dr. Avrum Spira. In her short time on faculty, she has established her research laboratory where her group is investigating the molecular events associated with the progression of premalignant lung lesions to identify novel chemoprevention strategies. Sarah’s group has a particular interest in characterizing clinical samples from pre-cancerous lung lesions as part of the Lung Pre-Cancer Atlas (PCA) part of the NCI- Human Tumor Atlas, which aims to enable the discovery of novel epithelial and immune modulations that are involved in the progression premalignant lesions to frank carcinoma to identify mechanisms to intercept the disease process. This pilot study will be an extension of that work and will take advantage of a new technology, Image Mass Cytometry, brought to BU through sponsored research programs, which her research team hopes this pilot will bring new opportunities for future NIH/NCI R01 funding in collaboration with her co-investigators.
Dr. Jennifer Beane is an Assistant Professor of Medicine at Boston University School of Medicine in the section of Computational Biomedicine. Jennifer earned her Ph.D. in Bioinformatics at Boston University, where she remained for her postdoctoral work. Jennifer joined the BU faculty in 2011 where her research interests focus on developing and implementing computational and statistical methodologies to expand our knowledge of the molecular changes that occur in the airway field on injury associated with smoking and lung cancer. Towards this goal, her research group has leveraged bulk and single-cell transcription data and to identify gene expression changes associated with smoking, lung cancer premalignancy, and lung cancer to develop clinically relevant biomarkers and new lung cancer interception therapies. Jennifer’s expertise in lung biology and informatics is well suited to lead the analysis of this pilot study and to establish analysis pipelines for image mass cytometry data that can be adopted for future funded applications.
Dr. Eric Burks is a Clinical Associate Professor of Pathology at the Boston University School of Medicine and the Medical Director for Hematopathology and Immunohistochemistry at Boston Medical Center. After graduating from medical school at the University of New Mexico School of Medicine, he had two fellowships: one in Surgical Pathology at Harvard Medical School and another in Hematopathology at Johns Hopkins Medical Institution. He joined the faculty at Boston University in 2018 where he brought extensive experience as a lecturer, mentor, and physician with a particular interest in lung cancer pathology. In his role as Medical Director for Hematopathology and Immunohistochemistry Eric has established a repository of well-annotated lung cancer samples that will be immune profiled as part of these studies to support additional funding opportunities for ongoing studies to establish biomarkers to better detect aggressive lung cancers.
Identifying Coding and Non-Coding Genomic Alterations Associated with Aggressive Prostate Cancer in African American Men
In collaboration with Drs. Joshua Campbell and Rachel Flynn, the overall goal of this pilot project is to identify coding and non-coding genomic alterations in the racially and socioeconomically diverse patient population surgically treated for prostate cancer at Boston Medical Cancer. In particular, we aim to identify a genomic signature associated with more aggressive disease in African American men, as well as establishing a pipeline to integrate these genomic data with other biomarker measurements (e.g. presence of ctDNA, microbiome signatures) and clinical outcomes in a larger cohort of men to create a comprehensive snapshot of these patients at the time of diagnosis and subsequently following treatment.
Meet the Team
Dr. Christopher Heaphy is a member of the Boston University-Boston Medical Center Cancer Center and is an Assistant Professor of Medicine and Pathology & Laboratory Medicine. His research program uses a combination of tissue-based, cell-based, and molecular approaches to study genomic alterations as it relates to cancer initiation and progression across a wide range of cancer types. In addition, his laboratory focuses on how the detection of these alterations may be readily translated into accurately predicting cancer risk, early detection, prognosis, and potential response to targeted therapies.
Dr. Joshua D. Campbell received his Ph.D. in Bioinformatics from Boston University. He performed his postdoctoral research at the Dana-Farber Cancer Institute and the Broad Institute of Harvard and MIT where he worked with The Cancer Genome Atlas (TCGA) to identify novel mutational drivers of lung cancer. He is currently an assistant professor in the Department of Medicine at Boston University School of Medicine where he utilizes genomic data to uncover biological mechanisms that may contribute to cancer disparities.
Dr. Rachel Flynn received her Ph.D. in Cancer Biology from the University of Massachusetts Medical School and conducted her Postdoctoral Fellowship in Molecular Oncology at the Massachusetts General Hospital at Harvard Medical School. Dr. Flynn is currently an Associate Professor in the Departments of Pharmacology & Experimental Therapeutics, and Medicine where the focus of her lab is to define the mechanisms regulating mammalian telomere maintenance and to understand how defects in this process contribute to tumorigenesis. She hopes these studies will allow her lab to gain the mechanistic insight necessary to identify novel targets and/or strategies in the treatment of cancer.
Liver-dependent Lung Remodeling and Pneumonia Susceptibility During Sepsis
It has long been known that systemic inflammatory events, such as those inherent to sepsis, tremendously predispose patients to hospital-acquired lung infections. Yet, the biological pathways influencing lung immunity during sepsis are poorly understood. Dr. Lee Quinton’s research has now established that liver responses to systemic inflammation calibrate the immunological tone of lung tissue, increasing its capacity to respond to subsequent infections. This study will leverage liver-specific mutant mouse models and single-cell sequencing to delineate cell-specific changes within the lung that rely on intact liver function, pursuing the hypothesis that during sepsis, liver activity dictates the transcriptional fingerprint of lung cells, including alveolar macrophages, to limit pneumonia susceptibility.
Dr. Lee Quinton is an Associate Professor of Medicine, Microbiology, and Pathology. He joined the faculty in the Pulmonary Center in 2008 after completing his post-doctoral fellowship at the Harvard School of Public Health. Dr. Quinton’s research program focuses on molecular mechanisms governing immunity and tissue protection during pneumonia. In particular, his laboratory has identified liver activation as a conduit through which early response cytokines promote local and systemic defense in response to lung infections. Additional investigations in Dr. Quinton’s laboratory are focused on deciphering signals controlling epithelial barrier integrity in the pneumonic lung, with the specific goal of determining when, where, and how lung cells collaborate to limit inflammatory injury.
Modeling the Anemia Elicited by Chronic Kidney Disease in Zebrafish
The goal of this research is to uncover how the interplay between microRNAs and uremic solutes orchestrate the responsiveness to erythropoiesis-stimulating agents (ESA) in chronic kidney disease (CKD). To this end, this project will model the anemia of CKD using zebrafish embryos as a model system. Preliminary data suggest a protective role of miR-451 in front of the oxidative stress induced by the uremic milieu. The findings from this project will have the potential to be developed into biomarkers and drug targets to enhance the precision of ESA therapeutics.
At the intersection of uremic toxicity and microRNAs, this proposal is innovative because it probes, for the first time, the effect of a set of uremic solutes on microRNA biogenesis, examines zebrafish as a model of uremic toxicity and the mechanism of ESA-responsiveness in end-stage renal disease patients. The novelty of the proposal is driven by an interdisciplinary team experienced in microRNAs and zebrafish (Dr. Cifuentes), and uremic toxicity (Dr. Chitalia).
Meet the Team
Dr. Daniel Cifuentes is an Assistant Professor in the Department of Biochemistry at the Boston University School of Medicine. Dr. Cifuentes received his Ph.D. from the University of Barcelona, Spain, for his studies in metabolic regulation. He completed his postdoctoral training in the Department of Genetics at Yale University School of Medicine, where he specialized in microRNA biology and vertebrate embryogenesis. His research goals at Boston University combine high-throughput genetic, genomic, and proteomic approaches to address fundamental questions of RNA regulation in viral and vertebrate systems.
Dr. Vipul Chitalia is an Associate Professor of Medicine at Boston University School of Medicine and an attending nephrologist covering renal consults, dialysis, and kidney transplant in-patient services as well as an affiliation to Harvard-MIT Division of Science and Technology, MIT. Teaching is his passion and he considers it an honor to be able to contribute to the training of the next generation of physicians, scientists, and physician-scientists. He strongly believes that a true mentor is one who inspires passion from within and empowers a mentee to find his or her own path of success.
Multimodal Microscopic Characterization of Novel Humanized Mouse Models of COVID-19
Improved animal models that faithfully recapitulate histologic phenotypes of severe COVID-19 are needed to enhance our understanding of host and viral determinants affiliated with SARS-CoV-2 pathogenesis. Current animal models fall short in that they either result in mild subclinical disease reflective of most COVID-19 cases or result in fatal neuroinvasion that is not documented in humans. In collaboration with Drs. Florian Douam (Boston University), Alex Ploss (Princeton), and Alejandro Balazs (Ragon Institute), we will microscopically characterize humanized mice engrafted with human lung xenografts in the absence and presence on concurrent human hematopoietic stem cells (dual engrafted). We will utilize a broad array of microscopic techniques including histomorphology, transmission electron microscopy, and multiplexed immunofluorescent immunohistochemistry to systemically characterize the immunopathologic landscape of these humanized mouse models. Because of the ability of our mouse model to integrate a multi-layer functional human immune response, we hypothesize this project will provide unprecedented insights into the cellular and molecular mechanisms that define SARS-CoV-2 immunopathogenesis and severe COVID-19 disease. Importantly, our findings will be integrated with transcriptomics and proteomics datasets to elucidate specific biological pathways driving morphomolecular findings. Through a better understanding of these mechanisms, this work will open significant opportunities for the development of better-targeted therapeutics and immunotherapies against COVID-19.
Dr. Nicholas Crossland is a veterinary pathologist, Assistant Professor in the Department of Pathology, and the director of the NEIDL’s Comparative Pathology Laboratory (NCPL) core. His team provides pathology expertise to NEIDL investigators and their respective laboratories working in BSL-3 and BSL-4. His research interest is in the systematic multimodal microscopic characterization of animal models to better define pathogenic mechanisms of emerging infectious diseases. He also finds fulfillment in utilizing his expertise to evaluate the efficacy of vaccines and therapeutics in preclinical models as a means to prevent and/or alleviate human suffering.
Non-invasive Blood Flow to Predict Recovery from Coma in Brain Injured Patients
We aim to determine the effect of cerebral blood flow on coma recovery, testing the hypothesis that non-invasive cerebral blood flow measurements following acute brain injury can predict recovery. We will use a novel non-invasive monitor to determine CBF, continuously following admission in stroke, traumatic brain injury (TBI), and post-cardiac arrest comatose patients. We will also evaluate the effect of skin color on non-invasive optical blood flow measures, with the understanding that skin color may introduce a correctable bias in cerebral blood flow measurements in awake and comatose brain patients, important to our diverse populations at BU/BMC.
Dr. David Greer is Professor and Chair of the Department of Neurology at Boston University School of Medicine and the Richard B. Slifka Chief of Neurology at Boston Medical Center.
Dr. Greer is the editor-in-chief of Seminars in Neurology, and the immediate past editor-in-chief for Neurocritical Care ON CALL. He has authored more than 250 peer-reviewed manuscripts, reviews, chapters, guidelines, and books.
His research interests include predicting recovery from coma after cardiac arrest, brain death, and multiple stroke-related topics, including acute stroke treatment, temperature modulation, and stroke prevention.
Dr. David Chung is a neurointensivist and translational neuroscientist in the Department of Neurology. He completed his MD/PhD and Neurology residency at Columbia University and a fellowship in Neurocritical Care at Harvard-MGB. Dr. Chung is an expert in cerebral blood flow and is dedicated to finding ways to improve long-term outcomes in patients with acute brain injury.
Dr. David Boas is a professor in Biomedical Engineering. His research areas of interest are: Neurophotonics, Biomedical Optics, Oxygen delivery and consumption, Neuro-vascular coupling, Physiological Modeling
Patient Perspectives on Disrespect and Abuse in Maternity Care
Experiences of disrespect and abuse during childbirth in healthcare facilities have been associated with subsequent PTSD, avoidance of maternal health services, and increased risk of maternal morbidity and mortality. This global human rights issue has largely been reported in low and middle-income countries but is under-investigated in the United States and Europe. Limited data on women’s experiences in the United States indicate meaningful rates of disrespect and abuse, with significant racial and ethnic disparities. Given the disproportionately increasing rates of pregnancy-related mortality and severe morbidity among minoritized racial groups in the United States, it is imperative that we understand the factors and specific behaviors that contribute to these experiences of disrespect and abuse during maternity care. This study will use mixed methods to assess the prevalence and experiences of disrespect and abuse among women delivering at Boston Medical Center (BMC). Our findings will serve as pilot data for a planned March of Dimes grant.
Dr. Tejumola Adegoke is an Assistant Professor of Obstetrics & Gynecology (OBGYN) at Boston University School of Medicine (BUSM) and an attending physician in the Department of OBGYN at Boston Medical Center (BMC). She is a clinician-investigator who provides full-scope reproductive and gynecologic care at BMC to human immunodeficiency virus (HIV)-infected patients at the BUSM/BMC’s Centers for Infectious Diseases. Her research focuses on eliminating injustice in form of disparate perinatal and gynecologic care experiences and outcomes for Black women. Dr. Adegoke received her undergraduate degree from Princeton University and obtained her medical degree from Rutgers – Robert Wood Johnson Medical School. She also earned her Master of Public Health from the Johns Hopkins Bloomberg School of Public Health and medical degree from Rutgers – Robert Wood Johnson Medical School. Dr. Adegoke completed a residency in Obstetrics and Gynecology at Boston Medical Center and joined the faculty in 2018. She serves as the department Director for Equity & Inclusion and represents the ACOG in Massachusetts’ state commission on racial inequities in maternal health.
Dr. Rachel Cannon is an Assistant Professor in Obstetrics and Gynecology at Boston University School of Medicine and an attending physician in the department of Obstetrics and Gynecology at Boston Medical Center. She provides full-scope OBGYN care and specializes in complex contraception and abortion. Her academic research interests include contraceptive counseling, reproductive justice, and health equity. She co-chairs the Health Equity Committee in the Department of OBGYN.
Dr. Cannon completed an undergraduate degree in Human Physiology at Boston University. She then completed her medical degree at the University of Massachusetts followed by a residency in OBGYN at Northwestern University. She specialized in abortion and complex contraception by completing a fellowship in Family Planning at Boston Medical Center. While in fellowship, she earned a Masters of Science in Health Services Research through Boston University School of Public Health. She advises the Boston University School of Medicine ACOG OBGYN Interest Group. Dr. Cannon serves as Ryan Program Director in the Department of OBGYN residency program and is responsible for the family planning curriculum for OBGYN residents.
Dr. Katharine Hutchinson is an Assistant Professor in Obstetrics and Gynecology at BUSM and an attending midwife at BMC. She is the Co-Director of Advocacy Initiatives for the Department and provides full-scope midwifery care to clients at BMC. Her research interests include Respectful Maternity Care and patient experiences of birth during COVID.
Dr. Hutchinson completed her undergraduate degree at Swarthmore College, followed by her midwifery training at Yale University, and her doctorate at BUSPH. Her dissertation examined access to emergency obstetric care for preeclamptic and eclamptic patients in Port au Prince, Haiti.
Prediction of Knee Pain Using Ultrasound Imaging and Machine Learning
This project (in collaboration with Dr. Juan-Pablo Lopez-Zertuche Ortiz, Dr. Eugene Kissin, and Dr. David Felson) proposes to develop advanced machine learning approaches that can process ultrasound images to predict knee pain.
Meet the Team
Dr. Vijaya Kolachalama is an Assistant Professor within the Department of Medicine, Boston University School of Medicine and the Department of Computer Science, Boston University, and a founding member of the Faculty of Computing & Data Sciences at Boston University. Research in his group is focused on developing advanced machine learning algorithms that have diagnostic relevance. His laboratory is funded by multiple awards from the National Institutes of Health, American Heart Association, private foundations, and the pharmaceutical industry. His course entitled Machine Learning for Biomedical Applications attracts a diverse set of individuals with little to no background in computer science.
I serve as the program director for the rheumatology fellowship program and have a shared focus in medical education and in musculoskeletal ultrasound development. I helped found and lead the training program for USSONAR, the preeminent group for musculoskeletal ultrasound education in North America. I was selected to the American College of Rheumatology (ACR) Core Expert Panel for appropriateness criteria for musculoskeletal ultrasound use in rheumatology as well as the ACR musculoskeletal ultrasound task force and RhMSUS Development Project for musculoskeletal ultrasound certification. In addition, I am responsible for medical student and resident rheumatology rotations at Boston University Medical Center.
Role of ZEB2 in Pericytes Development and Renal Fibrosis
The goal of this pilot grant is to elucidate the role of ZEB2 in kidney fibrosis. ZEB2 is a SMAD-interacting transcriptional factor and is expressed in Foxd1+ stromal cells that are progenitors for pericytes and fibroblasts during kidney development. Pericytes and fibroblasts are the key cell types contributing to the myofibroblasts during kidney fibrosis. We will analyze the histopathological changes in the kidneys of Zeb2 stromal-specific conditional knockout mice (Zeb2flox/flox; Foxd1Cre+) which developed kidney fibrosis. The outcome of this project will help understand the cellular and molecular mechanisms of kidney fibrosis and pericyte/fibroblast development.
Dr. Sudhir Kumar is an assistant professor of medicine in the Nephrology Section, Department of Medicine at Boston University School of Medicine. His research work focuses on Slit-Robo signaling in kidney diseases and podocyte biology and ZEB2 signaling in kidney development and diseases using animal models. Dr. Kumar received his Ph.D. from Ludwig Maximilians University Munich, Germany, and completed his postdoctoral training in Dr. Weining Lu’s lab, Nephrology Section at Boston University School of Medicine.
SARS-CoV-2 Diversity and Transmission Among Healthcare Personnel
Healthcare personnel (HCP) have been disproportionately affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however little is currently known about where and under what conditions SARS-CoV-2 transmission occurs in clinical settings. This study will combine viral whole-genome sequencing with rich epidemiological and contact tracing data on a unique cohort of healthcare workers and nosocomial patient cases spanning the initial COVID-19 surge in Boston. With a team of experts from Boston Medical Center, Boston University School of Public Health, and the Boston University National Emerging Infectious Diseases Laboratory, we aim to uncover how SARS-CoV-2 transmission in the hospital setting was successfully extinguished and identify circumstances where outbreaks persisted. A better understanding of SARS-CoV-2 transmission dynamics among healthcare workers and their patients will provide essential information for limiting hospital transmission in the ongoing pandemic.
Meet the Team
Dr. Tara Bouton is an assistant professor of medicine in the Section of Infectious Disease at Boston University School of Medicine. Her primary research interests are in the clinical and molecular epidemiology and genomics of drug resistance of tuberculosis and the impact of HIV co-infection. However, over the last year, she has served as co-investigator in two COVID-19 clinical trials and helped to develop a large healthcare worker SARS-CoV-2 cohort study using viral whole-genome sequencing to understand nosocomial transmission dynamics. She is currently PI on a prospective effort to bring near real-time sequencing to infection control at BMC.
Dr. John Connor is an Associate Professor of Microbiology at Boston University School of Medicine and an investigator at the National Emerging Infectious Diseases Laboratory. He leads a team of researchers that are studying the virus-host interaction through a variety of strategies including photonics, molecular virology, cell biology, and different omics approaches. These efforts include discreet programs in developing antiviral drugs, light-based diagnostics, and predictive/prognostic biomarker ID to help identify and treat viral disease. These studies have in the past focused on diseases like Ebola, Marburg, and Lassa Fever. During the COVID-19 pandemic, his laboratory has been heavily involved in mapping SARS-CoV-2 transmission through populations by analyzing the virus genome from patient samples and tracking its evolution.
Soft Robotic Technologies Enabling Safe Laparoscopic Bowel Manipulation
Laparoscopy is a minimally invasive technique to perform abdominal surgery through multiple small incisions in the abdomen. While this technique provides considerable advantages to the patient, it introduces several challenges to the surgeon that needs to carry out complex procedures with simple surgical tools, consisting of a long shaft with a distal end effector.
This becomes critical when manipulating delicate anatomical structures and can negatively affect the outcome of a procedure as well as the range of tasks that can be performed. Issues in laparoscopically manipulating delicate organs are caused by: 1) the inadequacy of tools in terms of dexterity and lack of compliance; and 2) the inability to sense applied mechanical stress.
This project’s endpoint will be the development of a soft atraumatic tissue manipulator for laparoscopic retraction of the bowel by exploiting soft robotic technologies. Safe and effective endoluminal tissue manipulation will be guaranteed by the design and constituent materials used for the construction of the manipulator, and through integrated pressure sensing elements that will monitor the interaction with tissues.
The proposed work will be carried out in collaboration with Donald Hess, MD, (Co-PI) Assistant Professor of Surgery, Boston University School of Medicine, Chief, Section of Bariatric Surgery, and Director of the Bariatric Surgery Program.
Dr. Tommaso Ranzani is an Assistant Professor in the Department of Mechanical Engineering, Biomedical Engineering, and in the Division of Materials Science and Engineering at Boston University. He received a Bachelor’s and Master’s degree in Biomedical Engineering from the University of Pisa, Italy. He did his Ph.D. at the BioRobotics Institute of the Sant’Anna School of Advanced Studies, and he joined the Wyss Institute for Biologically Inspired Engineering at the Harvard John A. Paulson School of Engineering and Applied Sciences as a postdoctoral fellow in 2014.
At Boston University, he founded the Morphable Biorobotics Lab. The lab focuses on expanding the potential of soft robots across different scales to develop novel reconfigurable soft-bodied systems with applications ranging from environmental exploration to assistive and soft surgical robots.
Dr. Donald T. Hess is a graduate of Williams College in Williamstown, MA, and received his medical degree from the University of Rochester School of Medicine and Dentistry in Rochester, NY. He completed a residency in general surgery at Beth Israel Deaconess Medical Center (BIDMC) in Boston, MA, and a research fellowship in Surgical Oncology at New England Deaconess Hospital in Boston, MA. He started at Boston University Medical Center after working for the US Air Force as an Assistant Professor of Surgery stationed at Wright-Patterson Air Force Base (WPAFB) in Ohio.
His clinical practice is devoted to minimally invasive and bariatric surgery. He has tremendous surgical expertise in laparoscopic bariatric surgery (sleeve gastrectomy and gastric bypass) and revisional bariatric surgery. He also has an interest in minimally invasive surgery, robotic surgery, surgery for disease of the stomach and esophagus, intestinal surgery, single-site surgery, complex hernia surgery, and general surgery. He is also the program director of the General Surgery residency and is heavily involved in surgical education.
Dr. Hess is involved in many research protocols involving metabolic and cardiovascular disease in patients undergoing bariatric surgery. He is a member of the Association of Metabolic and Bariatric Surgeons, the Society of American Gastrointestinal and Endoscopic Surgeons, a fellow of the American College of Surgeons (ACS). He has been recognized by Boston Magazine’s “Top Docs” issue for being “top” in his respective field since 2009 and was a 2013 recipient of the Boston University School of Medicine Evans Center Collaborator of the Year Award.
Validating the Role of Extracellular Matrix Molecules in Parkinson’s Disease Using Mass Spectrometry Glycomics and Proteomics
Brain extracellular matrix (ECM) consists of hyaluronan, glycosaminoglycans (GAGs), proteoglycans (PGs), glycoproteins, and a variety of post-translational remodeling proteases. GAGs and PGs play intricate roles in neuronal processes, including axonal growth/degeneration, synaptic plasticity, and neurite outgrowth in neurodegenerative disorders, including schizophrenia, Alzheimer’s disease, and Parkinson’s disease (PD). Importantly, ECM networks modulate axonal growth/degeneration and synaptic dysfunction that contribute to PD. Thus, ECM abnormalities may denominate the dysregulation of these processes in PD. However, despite the apparent importance of the ECM molecules to neurodegeneration, little information is available on the levels and structural alterations of these molecules in ECM of PD brains. A relatively low number of mass spectrometry-based proteomics and glycomics studies have been reported for PD. Thus, this modality for identifying PD-associated targets and pathways remains under-explored for understanding underlying PD pathophysiology.
We assessed the structural alterations of GAGs and proteins in the human PD brain prefrontal cortex relative to controls in two separate cohorts using ultra-high-performance mass spectrometry proteomics and glycomics technology. We identified alterations to GAG structure and enrichment of ECM constituents in the PD brain. This is the most extensive glycomics and proteomics study on PD to date. For any cohort-based study, the only way to eliminate all possible sources of bias related to tissue procurement and processing is to repeat the work using separate biospecimen cohorts in future studies. Thus, we will validate these findings using two new cohorts similar to our previous work, consisting of 12×12 PD and age-matched non-neurological disease controls, instead of one large validation cohort, because of various challenges associated with increasing sample size, including degrading quantitative quality, snowballing missing data and false‐positive discovery of altered proteins. For this study, we will refine our data quality control and acquisition to enhance our ability to assess the findings of our previous study. Our unbiased and nuanced view of alterations of ECM glycans, proteins, and genes will solidify our knowledge of PD pathology and uncover targets for more effective and preventive therapeutic strategies.
We will conduct this work at the BU Center for Biomedical Mass Spectrometry, where Dr. Sethi (PI of the project) works as an Instructor. The biospecimens will be provided by Dr. Thor D. Stein, a neuropathologist at the BU-VA-CLF Brain bank, who will serve as a Co-PI on the project.
Dr. Manveen K. Sethi serves as Instructor of Biochemistry at the Boston University School of Medicine, USA. She did her Ph.D. at Macquarie University (MQ), Australia, under the primary supervision of Dr. Morten Thaysen-Andersen, where she utilized mass spectrometry proteomics and glycomics analysis to understand underlying molecular mechanisms in colorectal cancer. After her Ph.D., she joined Boston University School of Medicine (BUSM), USA, as a postdoctoral associate under Prof. Joseph Zaia, where she is currently employed in a research faculty-track position of Instructor. Her research work involves identifying and characterizing biomolecules such as proteins and glycans using mass spectrometry techniques and utilizing this information to understand biomolecular deregulation in human diseases, such as cancer and Alzheimer’s disease. Recently, she received a Bright Focus Foundation fellowship award to investigate extracellular matrix changes in Alzheimer’s disease.
Dr. Thor Stein is Associate Professor of Pathology and Laboratory Medicine and Associate Director of the Neuropathology Core of the BU Alzheimer’s Disease Center as well as staff neuropathologist at the VA Boston Healthcare System (VABHS). Dr. Stein’s research interests involve the study of neurodegenerative diseases, including chronic traumatic encephalopathy (CTE), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS). He studies the role of trauma in the development and acceleration of multiple types of neurodegenerative disease. He has published extensively on the development and modeling of age- and trauma-related neuropathologies, including the most comprehensive studies to date on beta-amyloid deposition, cerebral amyloid angiopathy, and Lewy body disease following repetitive mild traumatic brain injury. Dr. Stein is the Principle Investigator on numerous grants, including a VA Merit Award on the role of traumatic brain injury in the development of AD and CTE as well as multiple NIH R01s, focused on determining the link between epigenetic modifications, lipidomic profiles, and pathological changes in the brain as they relate to cognitive decline.
2020 Integrated Pilot Grant Awardees
Peer Recovery Coaching for HCV and Opioid Use Disorder Treatment
The U.S. opioid epidemic is associated with a surge in hepatitis C virus (HCV) infections among persons who inject drugs. Despite the availability of curative therapy, treatment uptake remains low in this group. The goal of this study is to determine the feasibility and acceptability of a peer intervention to improve linkage to HCV care, treatment initiation, and cure among individuals with a history of opioid use disorder. Our findings will serve as pilot data for a planned NIH R01 proposal.
Sabrina A. Assoumou, MD, MPH, is Assistant Professor of Medicine at Boston University School of Medicine and an attending physician in the section of Infectious Diseases at Boston Medical Center. She is a clinician-investigator who provides care to human immunodeficiency virus (HIV)-infected patients at the BUSM/BMC’s Centers for Infectious Diseases. Her research focuses on medical complications of substance use including HIV and hepatitis C virus (HCV). She is also interested in models of care and improving the continuum of care for individuals with HIV/ HCV. She is currently the Principal Investigator on a NIH K23 Mentored Career Development Award to improve linkage to care after testing for HIV and HCV at a drug detoxification center.
Dr. Assoumou graduated magna cum laude from Williams College and obtained her medical degree from the University of Rochester School of Medicine and Dentistry. She then completed a combined Internal Medicine-Pediatrics residency at Brown University and an Infectious Diseases Fellowship at Harvard University’s Beth Israel Deaconess Medical Center where she was awarded the Finland Award for Research Excellence. She also earned a Master of Public Health at the Harvard T.H. Chan School of Public Health. Dr. Assoumou received an Excellence in Teaching Hospital-Based Faculty Award at BMC in 2017. She was also recognized as the Distinguished Faculty of the Month in April 2020 for her service to the BUSM community in teaching, activities on committees, and the mentoring of students, trainees, and junior faculty.
Data-Driven Youth-Led Health Promotion Strategy for a Safety Net Accountable Care Organization
The “Data-Driven Youth-Led Health Promotion Strategy for a Safety Net Accountable Care Organization” is a partnership between researchers at the Boston University School of Social Work and Boston Medical Center’s Department of Family Medicine. The overall goal of the project is to develop and vet a youth-driven health promotion campaign informed by a youth-led health assessment. The research will be guided by a youth advisory board consisting of six to eight youth of color who will be trained in the principles of youth participatory action research (YPAR), health equity, the social determinants of health, health promotion practice, and data-driven planning.
Astraea Augsberger is an Assistant Professor at Boston University School of Social Work. She earned her MSW and Ph.D. from Columbia University. She has over a decade of clinical practice experience with children, youth, and families in the child welfare, juvenile justice and mental health systems. Her research interests include youth civic engagement, youth development, child welfare policy and programs, and health equity. She employs community-engaged research, youth participatory action research, and in-depth qualitative research methods to elevate the voices of youth and communities in identifying research priorities and relevant solutions to community concerns. She is an affiliated faculty member of the Boston University Center for Innovation in Social Work & Health (CISWH) and the Boston University Initiative on Cities (IOC).
Dr. Katherine Gergen Barnett is the Vice-Chair of Primary Care Innovation & Transformation and the Program Director in the Department of Family Medicine at Boston Medical Center (BMC). Katherine joined BMC in 2009 after completing her residency and chief residency there. Prior to BMC, Dr. Gergen Barnett attended Yale University School of Medicine, worked at NIH, and completed a fellowship studying a model of group prenatal care for underserved women.
Dr. Gergen Barnett’s primary interests are behavioral health integration, preventive medicine, nutrition, mindfulness-based stress reduction, women’s health, and group care. Dr. Gergen Barnett’s research career has been primarily focused on innovative models of care to address chronic medical conditions, physician burnout, and engaging community partners in creating feasible solutions to increase health and wellness in urban communities.
“Immune Response and mEdical Complications of coVid-19 suRvivors (I-RECOVR) study”
The Study will follow a cohort of recovered patients to evaluate if those who survive acute illness with COVID-19 are at risk for continued physical disabilities or new medical sequalae, and whether these presentations are determined by initial disease severity or patient characteristics. Additionally, the study will follow this cohort over a two-year period of time to determine if survivors of COVID-19 are at risk for reinfection with SARS-CoV-2 and evaluate if incidence of reinfection or medical sequelae after recovery are associated with nature and longevity of immune response. Dr. Bhadelia serves as the principal investigator of a prospective biorepository study supported by a grant from Massachusetts Coalition for Pathogen Readiness and through internal support from Boston Medical Center. Currently, the study, entitled “Natural History of COVID-19 Confirmed Cases at Boston Medical Center (IRB H40047),” includes the longitudinal follow up of 200 hospitalized COVID-19 patients. This study is in the process of being expanded to cover 100 ambulatory COVID-19 patients and the two- year follow up of 200 COVID-19 survivors. The prospective study collects basic demographic and medical information as well as biological samples for use by Boston Medical Center and Boston University researchers. I-RECOVER study is layered on top of the survivor arm of this study and this pilot grant will be used to conduct survey tools, in person interviews, and collect biological samples for analysis mentioned above. The pilot data generated from the early part of I-RECOVER project will be used to support an R01 grant that will fund virologic and immunologic analysis on the stored samples as well as more extensive imaging of survivors with continued medical sequelae.
Dr. Nahid Bhadelia is an infectious diseases physician and the Medical Director of Special Pathogens Unit at Boston University School of Medicine, a medical unit designed to care for patients with highly communicable diseases. She is an Associate Professor in the Section of Infectious Diseases. She oversees the medical response program for Boston University’s maximum containment Biosafety Level 4 program at National Emerging Infectious Diseases Laboratories.
During the West African Ebola epidemic, she served as a clinician in several Ebola treatment units, working with World Health Organization and Partners in Health. She currently serves as the clinical lead for the Joint Mobile Emerging Disease Intervention Clinical Capability (JMEDICC) program which is a joint US-Ugandan effort to create clinical research capacity to combat viral hemorrhagic fevers in Uganda at the border of Democratic Republic of Congo. She serves on national and interagency groups focused on medical countermeasures, the intersection between public health preparedness, research, and clinical care for emerging pathogens. Her research focuses on identification of safe and effective clinical interventions and infection control measures related to viral hemorrhagic fevers.
She has served as a subject matter expert to US Centers for Disease Control and Prevention, Department of Defense, Global Fund to Fight AIDS, Tuberculosis and Malaria, and World Bank.
Dr. Bhadelia is also an Assistant Professor at the Institute of Human Security at the Tufts Fletcher School of Law and Diplomacy, where she teaches a course on human security and emerging infectious diseases. She received her Doctorate of Medicine from Tufts University and completed her internal medicine residency and chief residency at Mount Sinai Hospital in New York. Her Infectious Diseases Fellowship was completed at Columbia Presbyterian Hospital.
PTH/PTHrP Receptor Signaling in Osteocytes during Aging
Dr. Divieti Pajevic’s research is focused on studying the effects of hormones, such as parathyroid hormone, and mechanical forces on bone and teeth. Recently, her group has been investigating the cross-talk between bone and muscle and the effects of aging. In her current CTSI proposal titled “PTH/PTHrP Receptor Signaling in Osteocytes During Aging,” Dr. Divieti Pajevic will use a combination of genetically modified mice and cell lines to investigate if PTH signaling in osteocytes alters skeletal progenitors and protects these cells from senescence.
Paola Divieti Pajevic, MD, PhD, is an Associate Professor of Translational Dental Medicine at the Goldman School of Dental Medicine at Boston University and the Director of the Bone Cells Core which is part of the MGH-Center for Skeletal Research.
Lionoleic Acid Promotes Pathogenic T Cells in Type 1 Diabetes
Type 1 Diabetes is an autoimmune disease caused by T cells that destroy the insulin-producing beta-cells in the pancreas. The incidence of Type 1 Diabetes is rapidly rising worldwide due to currently unknown environmental factors that promote the autoimmune response in genetically susceptible individuals. There is growing evidence that specific metabolites derived from the diet or microbiome have the capacity to influence the functions of T cells and may promote pathogenic T cells in autoimmune diseases. We discovered that addition of the dietary fatty acid linoleic acid to in vitro T cell cultures altered the balance between pathogenic IL-21-producing and protective IL-10-producing T cell subsets in favor of the cells with pro-diabetic activities. The goals of this CTSI pilot grant are to test whether autoreactive T cells exposed to linoleic acid have an increased capacity to cause diabetes in vivo, and whether feeding diabetes-susceptible NOD mice a linoleic acid-rich diet will accelerate diabetes development. Our study has the potential to identify a dietary factor that is increasingly present in Western diets as a driver for increased Type 1 Diabetes susceptibility. This finding may form the basis to develop preventative dietary interventions in susceptible individuals and/or to target the metabolic and signaling pathways that underlie linoleic acid-based induction of diabetes-causing T cells.
Dr. Hans Dooms is an immunologist who currently holds a position as an Assistant Professor in Medicine and Microbiology at the Arthritis and Autoimmune Diseases Research Center of Boston University School of Medicine. He received his Ph.D. from Ghent University in Belgium and continued his training in immunology at the University of California San Francisco in the laboratory of Dr. Abul Abbas. His research interests are focused on the biology of T cells and their role in the autoimmune diseases Type 1 Diabetes and Systemic Sclerosis. His laboratory is currently studying how autoreactive T cells acquire and maintain their disease-causing properties and how these cells escape immune regulatory mechanisms aimed at preventing autoimmunity. Dr. Dooms has received funding for his research from NIH, JDRF, and the American Diabetes Association. He has authored 29 publications, many included in some of the most prestigious journals in the field of immunology.
Defining the Role of Hippo Pathway Inactivation in Melanomagenesis
Dr. Ganem’s CTSI award is focused on testing the hypothesis that inactivation of the Hippo tumor suppressor pathway plays an important role in melanoma development.
Neil J. Ganem is an Associate Professor in the Department of Pharmacology & Experimental Therapeutics, and Department of Medicine, Division of Hematology and Oncology. He directs the Laboratory of Cancer Cell Biology, where his team used a combination of high-resolution microscopy, genome-wide screening, bioinformatics, and animal model systems to understand the causes and consequences of genome instability in human cancer.
Primary Care Connection in Maine
Millions of Americans have gained health insurance under the Affordable Care Act’s Medicaid expansion. However, health insurance is only a first step toward the goal of improving population health; receipt of primary care is a critical follow-up step. Despite the array of known benefits of primary care, little empirical work has examined how states can encourage uptake of primary care among new Medicaid enrollees. To address this gap in the evidence, we propose to design and pilot test an intervention to increase engagement with primary care services among newly enrolled Medicaid beneficiaries in the state of Maine, in partnership with the Office of Member Services (OMS) at the Maine Department of Health and Human Services. The pilot study will be a single blinded, randomized, controlled trial of a behavioral intervention to increase the PCP visit rate within the first six months of new Medicaid enrollment. The treatment arm will receive a one to two page letter that encourages new enrollees to get a free checkup and recommends a single provider, located within 30 miles of the enrollee’s home address. Clinics will be notified of newly assigned patients and encouraged to reach out to schedule initial appointments. The control arm will receive the current MaineCare enrollee packet of 23-pages, including a comprehensive provider directory. We will assess acceptability and feasibility of our intervention to MaineCare members, providers, and our partners at OMS. If the pilot trial proves acceptable and feasible, we will plan to implement a larger scale trial within 6 months of the pilot’s end.
The research team for this project includes Anna Goldman, MD, MPA, MPH, of BUSM/BMC; Sarah Gordon, PhD, MPH, of BUSPH; and Benjamin Sommers, MD, PhD, of Harvard T.H. Chan School of Public Health.
Anna L. Goldman MD, MPA, MPH, is a general internist practicing primary care, and a health services researcher. Her research centers on the effects of insurance and payment policies on care access for the poor and undeserved. She focuses on the health insurance programs established by the Affordable Care Act, the Medicaid expansion and Marketplace insurance. She also investigates the effects of accountable care organizations (ACOs) in the Medicaid program on health care quality and access. She has a medical degree from Mount Sinai School of Medicine, a Master’s Degree in Public Health from the Harvard T.H. Chan School of Public Health,and a Master’s Degree in Public Affairs from Brown University. She completed an internal medicine residency at Cambridge Health Alliance.
Sarah Gordon is an Assistant Professor in the Department of Health Law, Policy, and Management at the Boston University School of Public Health. Her research is dedicated to studying coverage and access to care among low-income populations, with a particular emphasis on Medicaid policy. Her work seeks to understand how the fragmentation of the U.S. health insurance system impacts utilization, quality, and continuity of care. Dr. Gordon recent projects leverage state-level datasets, such as all payer claims databases, and quasi-experimental study designs to evaluate the effects of state-level policies. She received her doctorate in Health Services Research from the Brown University School of Public Health and a M.S. in Social and Behavioral Sciences from the Harvard T. H. Chan School of Public Health
A Tool to Identify PrEP Eligible Youth in Primary Care
Pediatricians are the most common provider of primary care for youth, and frequently provide care to individuals through their early-to-mid 20s. Thus, pediatric primary care offers an opportune setting for identifying youth who are eligible for pre-exposure prophylaxis (PrEP). To successfully identify PrEP-eligible youth, it is essential that pediatricians ask valid, developmentally appropriate screening questions that resonate with youth and elicit accurate information. The objective of this proposal is to conduct mixed methods, translational research to develop (Aim 1), and conduct a pilot study (Aim 2) of a HIV risk assessment tool that pediatricians can integrate into their current primary care practice to identify PrEP-eligible youth. Data from the pilot study will directly inform a subsequent clinical trial of a comprehensive PrEP service delivery model for pediatric primary care.
Scott Hadland is a pediatrician and addiction specialist at Boston Medical Center and Boston University School of Medicine. He holds triple board certification in General Pediatrics, Adolescent Medicine, and Addiction Medicine. Dr. Hadland’s clinical and research interests focus on adolescent and young adult substance use disorder prevention and treatment. In the proposed work, Dr. Hadland will extend his work into human immunodeficiency virus (HIV) prevention among youth, with a goal of enhancing pre-exposure prophylaxis (PrEP) delivery in pediatric primary care.
Influenza Induced Lymphangiogenesis
The overall objective of this proposal is to identify lymphatic-centered strategies to contain viral lung infections. To achieve this goal, the PIs use a mouse influenza model that allows for deciphering the functional therapeutic properties and origins of the markedly expanded pulmonary lymphatic system that the PIs found accompanies influenza. Based on preliminary data, the central hypothesis is that new lymphatic growth facilitates immunomodulatory events and alterations in lymphatic cell function that are central to virus containment. The PIs propose to use the CTSI pilot grant to perform a detailed transcriptional analysis of lymphatic cells as the lung responds to influenza.
The PIs driving this project are Dr. Matthew Jones and Dr. Alan Fine. Together, they have a successful history of collaboration on various projects, grants, and papers.
Dr. Matthew Jones is a lung molecular biologist with an extensive history of studying the lung’s response to infection. Dr. Jones also brings a deep knowledge of gene expression analytical methodology to this project.
Dr. Alan Fine is a practicing pulmonologist with broad experience in the treatment of lung disease. He has a long history of external funding that supports work aimed at understanding the fundamental biology of lung cells, lung development, and disease mechanisms.
Clinical Pipeline for Single Cell Profiling of Triple Negative Breast Cancer
The research for this CTSI pilot award will recruit, consent, and invite BMC patients with breast cancer to participate in translational research, by providing biopsy specimens for single-cell RNA sequencing to answer cutting-edge research questions on the behavior of tumor cells and the immune environment.
Dr. Naomi Ko is an Assistant Professor of Medicine at Boston University School of Medicine (BUSM) and a medical oncologist at Boston Medical Center (BMC). Her research is directed to understanding the root causes of cancer disparities, the disconnect between scientific discoveries in cancer treatment, and delivery of evidence-based treatment to vulnerable, racial/ethnic minority women with breast cancer. She is actively investigating how tumor biology, social, and treatment factors influence breast cancer outcomes in undeserved, diverse breast cancer populations.
Single-Cell Analysis of AL Amyloidosis Plasma Cells
Since starting at BUSM in 2018, Gareth has established a program to study the aberrant plasma cells that underlie AL amyloidosis, which is a rare but often fatal form of systemic amyloidosis. These plasma cells normally secrete antibodies as part of the adaptive immune system. Aberrant proliferation in bone marrow causes overproduction of antibodies and, in some cases, amyloidosis. Comparing the gene expression of these cells to that of healthy plasma cells and those from a related disease, multiple myeloma, should reveal specific vulnerabilities that can be targeted for therapy. The CTSI pilot grant will enable researchers from the Amyloidosis Center to measure single-cell gene expression profiles of primary cells isolated from patient bone marrow aspirates. This project brings together the clinical work of the BU Amyloidosis Center with the cutting-edge instrumentation in the Department of Medicine Single Cell Sequencing Core Facility. These experiments will enable larger-scale studies to identify therapeutic targets and prognostic markers that could help to optimize treatments and benefit patients.
Gareth Morgan is a Research Assistant Professor in the Section of Hematology and Medical Oncology at the Boston University School of Medicine, and a member of the BU Amyloidosis Center. Originally from the United Kingdom, Gareth completed his B.Sc. in Biochemistry from Imperial College, London. He received his Ph.D. from the University of Sheffield, where he worked with Professors Rosie Staniforth and Jon Waltho. Gareth worked as a postdoctoral research associate with Professor Sheena Radford at the University of Leeds, and then with Professor Jeff Kelly at the Scripps Research Institute in San Diego, CA. Throughout his career, Gareth has studied how proteins fold, misfold and aggregate. He is especially interested in understanding how cells and organisms manage and maintain their proteomes, and why these processes break down to cause systemic amyloidosis diseases, where accumulation of protein aggregates leads to progressive organ failure. A major research focus is on developing small molecule drugs that can prevent protein aggregation, which could benefit patients with these diseases.
Machine Learning Risk Stratification of Stroke in Patients with AF
We aim to develop a clinically-oriented risk prediction model of stroke in patients with non-valvular atrial fibrillation using novel, clinically-oriented machine learning methods and data from Boston Medical Center and the UK Biobank
Non-valvular atrial fibrillation (NVAF) is associated with a five-fold increased risk of stroke.1 The most widely used prediction scales to risk stratify patients include the CHADS22,CHA2DS2-VASc3, and Framingham Risk scales.1,4 These are commonly used to guide management decisions (anticoagulation or antiplatelet therapy) for primary or secondary stroke prevention. However, like many risk prediction scales, they assume that the addition of risk factors is cumulative and linear,5 which limits their discrimination (C statistics of 0.68-0.7 in large validated studies)6,7 and generalizability. Advances in machine learning (ML) methods allow us to model non-linear risk in large datasets, improving performance, making individualized risk stratification possible. Moreover, our group has developed a novel and interpretable tree-based ML method specifically tailored for clinical applications. Optimal classification trees (OCTs) is an ML method that improves accurate classification compared to traditional statistical methods, while allowing practitioners to easily identify risk factors that contribute to outcomes.8 Such interpretability resolves the “black-box” or opaque classification disadvantage intrinsic to using many ML techniques. Our group has used these methods to stratify patients at high risk for emergent surgery, to predict 10-year cardiovascular risk, and to make treatment recommendations in diabetic patients.5,9,10 ML methods have not yet been used to develop clinically-oriented risk prediction models in cerebrovascular diseases like stroke risk in patients with atrial fibrillation (AF). We propose an innovative approach using a variety of novel, OCT-based methods to improve personalized stroke risk stratification in patients with non-valvular AF. Improved risk stratification would profoundly impact the population’s cardiovascular health, as it can inform management for approximately 5.3 million Americans with AF.11
Charlene Ong, MD, MPHS, is an Assistant Professor of Neurology and Neurosurgery at Boston University, Visiting Assistant Professor at Harvard Medical School and Massachusetts Institute of Technology, and a clinical Neurointensive Care Physician at Boston Medical Center. She received her undergraduate degree at University of Pennsylvania, her MD at Columbia University and her Master’s in Population Health Sciences at Washington University School of Medicine. Her research focuses on data-driven tools that support clinical decision making and optimize outcome after acute brain injury. She has received foundational support from the American Brain Foundation, Philips-MIT, the Peter Paul Career Development Committee, and the Clinical and Translational Science Institute at Boston University. Her aim is to build a robust ICU data science program and follow a K-track path toward the eventual goal of becoming an independently funded researcher and recognized leader in the field of neurocritical care.
Soft Robotic Platform for Restoring Haptic Feedback in Robotic Surgery
Robotic surgery has improved minimally invasive surgical procedures and shortened learning curves for surgeons. However, during robot-assisted procedures, haptic feedback is not available to the surgeon, resulting in uncontrolled force application which can lead to intraoperative complications. Absent haptic feedback is reputed to be among the reasons that impede further spread of surgical robots.
The capability to sense and touch the anatomy realistically has the potential to increase safety and precision during robotic surgery, with better patient outcomes. In this proposal, we will focus on restoring haptic feedback in minimally invasive robotic surgery by developing a soft robotic platform consisting of a soft sensing unit, to monitor forces exerted during surgical tasks and transduce this information to a soft actuation unit, that will map tactile information back to the surgeon.
Sheila Russo is an Assistant Professor in the Department of Mechanical Engineering and the Division of Materials Science and Engineering at Boston University. Prof. Russo completed her Ph.D. degree at the BioRobotics Institute, Sant’Anna School of Advanced Studies, Italy. She completed her postdoctoral training at the Harvard John A. Paulson School of Engineering and Applied Sciences and the Wyss Institute for Biologically Inspired Engineering. She is the founder and director of the Material Robotics Laboratory at BU that aims at bridging the gap between material science and robotics, and focuses on design, mechanics, and manufacturing of novel multi-scale and multi-material biomedical robotic systems. Her research interests include medical and surgical robotics, soft robotics, sensing and actuation, meso- and micro-scale manufacturing techniques, and advanced materials.
Pre-Clinical Validation of Novel Gene Editing Approaches for Sickle Cell Disease
With the support of the CTSI pilot grant, Dr. Vanuytsel will further develop the sickle cell disease (SCD)-specific iPSC platform as a pre-clinical tool to validate the efficacy of novel therapeutic gene editing strategies across a diverse SCD patient population.
Although SCD patients all share the same point mutation in the beta globin gene, the surrounding genetic background determines the severity of their disease course and response to therapy. Currently, several gene editing strategies are being explored as potentially curative approaches in clinical and pre-clinical trials. While these developments are truly exciting, their safety and efficacy will require thorough validation across a variety of SCD backgrounds to make sure that an effective treatment can be assured for every patient. iPSCs present an unlimited source of material that can be differentiated into erythroblasts that capture the exact genetic background of a patient, and thus make an excellent screening tool that could help predict the safety and efficacy of a particular therapeutic approach in a given genetic background prior to engaging in costly and invasive treatments.
Kim Vanuytsel is a Research Assistant Professor in the Division of Hematology and Medical Oncology at Boston University School of Medicine and the Center for Regenerative Medicine (CReM). She obtained a PhD in Stem Cell and Molecular Medicine from the Katholieke Universiteit Leuven (KULeuven) in Belgium. As a postdoc in Dr. George J Murphy’s lab, she developed novel resources and tools to better understand and treat blood disorders. Her current research focuses on finding better solutions for sickle cell disease (SCD) patients by using patient-specific induced pluripotent stem cells (iPSCs) as a versatile platform to study the disease, screen for compounds that can ameliorate the condition, and explore potential curative gene editing approaches.
