Rising Star Faculty – Dr. Michelle R. Dawson

Metabolic Reprogramming Drives Physical Alterations in Invasive Cancer Cells

ABSTRACT:

Radiation and chemotherapy are standard cancer treatments; however, cancer and stromal cells that survive treatment may develop therapy-induced senescence or dormancy, which contributes to tumor recurrence and metastasis. Cancer cells that survive chemotherapy may develop treatment resistance, which is associated with poor patient outcomes. Thus, there is an urgent need to investigate the mechanisms by which cancer cells escape therapy-induced dormancy to give rise to new tumors.

The Dawson Lab uses a single cell biophysical approach to study tumor microenvironment interactions in 2D and 3D tissue matrices. This microenvironment, which is both dynamic and heterogeneous in nature, plays a critical role in cancer progression from the growth of the primary tumor to the development of metastatic and drug-resistant tumors. Our single cell biophysical approach, is used to systematically investigate the parameters in the tumor that control cancer cell interactions with the stroma and to identify specific conditions that induce tumor-promoting behavior, along with strategies for inhibiting these conditions to treat cancer.

My presentation will focus on our recent work looking at metabolic reprogramming in invasive subpopulations of chemoresistant cancer cells, including polyploidal giant cancer cells (PGCCs). PGCCs represent a small subpopulation of non-mitotic cancer cells that evades treatment through periods of transient dormancy and then relapses into full-blown disease through amitotic budding. I will discuss ways the unique biophysical properties of PGCCs, including their giant size and high density of actin stress fibers and dispersed vimentin intermediate filaments, are linked to their dysregulated metabolism.

NARRATIVE BIOSKETCH:

Dr. Michelle Dawson is an Assistant Professor of Molecular Biology, Cell Biology, and Biochemistry at Brown University. She received her B.S. in Biomedical Engineering from Louisiana Tech University, Ph.D. in Chemical and Biomolecular Engineering from Johns Hopkins University, and completed her postdoctoral research in Rakesh Jain’s lab at Harvard Medical School / Massachusetts General Hospital. Her research uses quantitative single cell biophysical analysis to probe mechanisms contributing to the development of invasive and therapy-resistant cancers. Her current studies are investigating the link between stromal cell senescence and cancer progression. Studies at the intersection between cancer and aging research are critical in understanding how age-associated changes in the tumor microenvironment contribute to cancer progression. Her studies have identified novel biomarkers for senescent cells and treatment strategies targeting aggressive cancer cells that form in an aging stroma.