Rising Star Faculty – Dr. Kimberly Stroka

Form, Function, and Mechanics of Cell-Cell Junctions in the Vascular Endothelium

ABSTRACT:

Endothelial cells (ECs) have been recognized in the past several decades as transducers of mechanical forces such as hemodynamic shear stress, cyclic strain, matrix mechanics, and cell-cell physical interactions. ECs connect to and communicate with each other, through both biological signaling and biomechanical forces, via multiple types of adherens, tight, and gap junction proteins. For example, the cell-cell junctions of the endothelial cells in the blood-brain barrier (BBB) regulate numerous physiological processes, can break down in disease settings, and often present a barrier to drug delivery. Numerous studies, including our own, have demonstrated qualitative alterations in brain endothelial cell-cell junction phenotypes in response to distinct biochemical or biomechanical cues. Recently, we published a novel Python-based software, the Junction Analyzer Program (JAnaP), to quantify, in a rigorous and comprehensive manner, these cell-cell junction phenotypes from images of cell monolayers. We have used this program to evaluate the impact of microenvironment cues, such as matrix stiffness and tumor-secreted factors, as well as new light-based BBB drug delivery mechanisms, on endothelial cell barrier integrity and junction morphology. Meanwhile, conventional assays for evaluating functional barrier integrity (e.g., trans-endothelial electical resistance and transwell permeability assays) only provide global, single-measurement proxies for cell-cell junctions integrity across an endothelium. Hence, we have combined the JAnaP output with a local permeability assay to directly correlate cell-cell junction phenotype with local barrier function. Our work has provided new insights into the relationship between the form (phenotype), function (permeability), and mechanics of endothelial cell-cell junctions, and how these features may be biologically- and mechanically-regulated to produce spatial heterogeneity and temporal dynamics of barrier integrity within the endothelium.

NARRATIVE BIOSKETCH:

Dr. Kimberly Stroka is currently an Associate Professor in the Fischell Department of Bioengineering at the University of Maryland, College Park. Her lab explores the role of mechanical forces in physiological and pathological phenomena. To accomplish this goal, they engineer and probe in vitro models of multi-scale biological systems using bioengineering tools such as microfabricated devices; novel combinations of cells, molecular biology techniques, and cell mechanics tools; and custom quantitative image processing software. Dr. Stroka’s lab uses this framework in three main focus areas: (1) exploring the mechanobiology of the vascular endothelium in the context of health, disease, and drug delivery; (2) probing cell-cell interactions at the blood-brain barrier during tumor metastasis; and (3) engineering cellular microenvironments to understand mechanisms of cell adhesion, migration, and division.

Dr. Stroka received her Ph.D. in Bioengineering in 2011 from the University of Maryland, College Park and her B.S. summa cum laude in Physics in 2006 from Denison University. In her PhD work, Dr. Stroka investigated the effects of blood vessel stiffening on endothelial cell biomechanics, leukocyte mechanosensing, and leukocyte transmigration, during a normal immune response and in the context of cardiovascular disease. Dr. Stroka completed her postdoctoral training at The Johns Hopkins University Institute for NanoBioTechnology. In her postdoctoral work, she integrated microfabrication, molecular biology, live cell imaging, and theoretical modeling in order to uncover a new mechanism by which metastatic tumor cells migrate through confined microenvironments. Dr. Stroka’s postdoctoral and predoctoral work were supported by an NIH NRSA F32 postdoctoral fellowship, NIH T32 postdoctoral fellowship, NIH NRSA F31 predoctoral fellowship, and NSF Graduate Research Fellowship. Dr. Stroka was also awarded the Burroughs Wellcome Career Award as she transitioned to her faculty position at UMD. She was the recipient of the 2014 Rita Schaffer Young Investigator Award from the Biomedical Engineering Society (BMES), was recognized as a 2019 Cellular and Molecular Bioengineering Young Innovator, and is the recipient of the NSF CAREER Award and NIGMS Maximizing Investigator’s Research Award (MIRA). She also received the 2017 Outstanding Young Scientist Award from the Maryland Academy of Sciences and Maryland Science Center. She received the 2018 and 2019 Faculty Teaching Award from UMD’s Fischell Department of Bioengineering, UMD’s Phillipp Merrill Faculty Mentor Award, and the 2020 E. Robert Kent Teaching Award for Junior Faculty from the Clark School of Engineering. Dr. Stroka is currently Director of the UMD BIOE Honors Program, co-Director of the UMD BIOE REU site, and co-Director of the NCI/UMD Partnership for Integrated Cancer Research.