This is a past event.

Chemical Engineering Research Seminar

Michelle R. Dawson

Assistant Professor of Medical Science
Department of Molecular Biology, Cell Biology, and Biochemistry and the Center for Biomedical Engineering
Brown University

Abstract

Radiation and chemotherapy are highly effective at killing cancer cells but cells that survive treatment often develop therapy-induced senescence (TIS). Since growth is arrested in TIS, this has been considered a positive treatment outcome; however, senescent cells remain metabolically active and develop a senescence associated secretory phenotype (SASP), which can promote cancer progression. In addition, a small number of cancer cells are able to escape this dormant state to contribute to tumor recurrence and resistance. PGCCs are a novel and understudied subpopulation of dormant and multinucleated giant cancer cells that exhibit multiple features of TIS. Although PGCCs share many characteristics with senescent cells, including their large size, arrested cell cycle, and SASP, they also differ from senescent cells, in their ability to escape TIS by undergoing amitotic budding to form new tumors. Increased numbers of large PGCCs are seen in late stage and metastatic cancers; yet, there is a significant gap in our understanding of what allows PGCCs to survive chemotherapy and undergo budding to form chemoresistant and mitotic cancer cells. Through single cell, multicellular, and tissue level studies, we investigated how their cytoskeletal alterations, dysregulated metabolism, and inflammatory SASP contribute to PGCC survival during treatment. Our data suggests that their unique biophysical properties are linked to their dysregulated metabolism and altered cell structure. This presentation will focus on our recent work investigating the role of TIS on cancer and stromal cell interactions in the tumor microenvironment. These studies provide critical information about how aging and TIS affect tumor microenvironments.

Bio

I am currently an Assistant Professor in the Department of Molecular Biology, Cell Biology, and Biochemistry at Brown University. My lab studies tumor-promoting environments or ‘niches’ for cancer progression. I earned my BS in Biomedical Engineering from Louisiana Tech University in 1999 (3.98 GPA) and my PhD in Chemical and Biomolecular Engineering from Johns Hopkins University in 2005. My PhD research, with Drs. Justin Hanes and Denis Wirtz, was focused on mucosal barriers to drug delivery in the cystic fibrotic lung. My research was the first to use particle tracking microrheology to study mucosal transport of drug delivery particles. After completing graduate school, I moved to Rakesh Jain’s lab at Massachusetts General Hospital to pursue my interest in cancer and embark in a new research area that would require intensive training. I studied tumor microenvironment interactions using bone marrow transplant mouse models of neoplasia. In 2008, I accepted my first faculty position in Chemical and Biomolecular Engineering at Georgia Tech. This position was not a great fit for my cancer research program and lacked the possibility to form strong clinical connections, which is a prerequisite for NIH cancer research funding. Despite these limitations, I trained over 40 students and postdocs and published more than 20 papers on single cell biophysical analysis of tumor microenvironment interactions. With the tools and expertise developed through all of these training experiences, I joined Brown University as an Assistant Professor of Medical Science in 2016 with the goal of establishing a more translational research program. Since moving to Brown, my work is thriving, with creative new research ideas and several NSF grants and a single PI R01 from the NCI. Since moving to Brown, I have established a brand-new research program at the intersection of aging and cancer and published multiple papers in leading journals, including PNAS, Scientific Reports, Cancers and Journal of Cell Science.

This program/lecture is partially funded/sponsored by the Visiting Professor Program which is funded by a grant to the Office of the Provost from the State of Michigan's King-Chavez-Parks Initiative.

Hosted by Pradeep K. Agrawal.