Researcher Spotlight: Maria Trojanowska, PhD

OCRI member, Dr. Maria Trojanowska, is a Professor of Medicine and Director of the Arthritis Center at Boston University School of Medicine. Dr. Trojanowska and her team investigate the molecular and cellular mechanisms regulating extracellular matrix (ECM) synthesis in healthy tissues and in pathological conditions. Their main area of research focuses on the pathogenesis of scleroderma or systemic sclerosis (SSc), a devastating autoimmune disease characterized by a distinct pathogenic triad of microvascular damage, dysregulation of innate and adoptive immunity, and generalized fibrosis in multiple organs. Specifically, the goal of Dr. Trojanowska and her team is to uncover how disregulated signaling pathways, including TGF-b, CTGF, PDGFRa, and PKCd/Fli1 lead to pathological fibrosis.

Another area of active investigation for the Trojanowska lab focuses on scleroderma vascular disease, which contributes significantly to the morbidity and mortality of patients with scleroderma. However, the mechanisms contributing to scleroderma vasculopathy and the relationship between vasculopathy and fibrosis are not well understood. Based on the clinical studies that implicated deficiency of specific transcription factors such as Fli1 or GATA6 in the vasculature of patients with scleroderma, Dr. Trojanowska and her team have generated a novel genetic mouse model that recapitulates many of the vascular features of SSc. Such models are instrumental in elucidating the mechanisms of vascular disease and for the discovery and validation of potential therapeutic targets to treat vasculopathy in patients with scleroderma. To date, no treatment has been proven effective in modifying the course of scleroderma. Identification of key alterations in the signaling molecules may allow for selective targeting of these pathways and development of novel therapeutic strategies.

Dr. Trojanowska has been an active member of the OCRI since its founding in 2011 and is co-director of the Etiology and Pathogenesis of Oral Cancer ARC. She collaborates closely with Professor of Oral and Maxillofacial Pathology Dr. George Gallagher, Associate Dean for Research and Professor in the Department of Molecular & Cell Biology Dr. Maria Kukuruzinska, Associate Professor of Medicine and Biostatistics at Boston University School of Medicine (BUSM) Dr. Stefano Monti, Associate Professor and Director of Clinical Oral Pathology Dr. Vikki Noonan, and Assistant Professor of Biochemistry at BUSM Dr. Bob Varelas in characterizing carcinoma associated fibroblasts (CAFs) in OSCC. Using input from the bioinformatic analysis implicating PDGFRa as an early marker of stromal activation in OSCC, subsequent analyses of OSCC tumor tissues confirmed abundant expression of PDGFRa on stromal fibroblastic cells, but not on tumor cells. Having a specific marker on stromal fibroblasts will allow for further selection and molecular characterization of those cells. Future studies will focus on the role of OSCC CAFs in activating tumor growth and progression. Reciprocal experiments will investigate factors produced by tumor cells involved in activation of CAFs.

Dr. Trojanowska is also collaborating with Clinical Professor in the Department of Speech and Hearing Sciences at BUSM Dr. Susan Langmore on a project related to dysphagia, a morbid condition that interferes with swallowing and proper nutrition. Dysphagia develops in about 50% of head and neck cancer patients treated with radiation therapy. Currently, there are no tools available to predict which patients will develop fibrosis. The goal of their collaboration is to develop diagnostic tools to predict the likelihood of fibrosis in patients undergoing radiation therapy. The team has collected biopsy specimens from six post-radiation patients, which were analyzed by microarrays. The gene expression patterns in those samples will be compared to patient clinical characteristics with respect to fibrosis. These important studies are currently in progress.