Allison Sharrow, PhD

My research interests focus on better understanding the causes of ovarian cancer chemoresistance and relapse.  Accordingly, I have primarily studied a relatively quiescent and chemoresistant subpopulation of ovarian cancer cells.  Quiescent cells are in a transient state of cell cycle arrest and can readily reenter the cell cycle and proliferate.  These cells have been found to be enriched after chemotherapy treatment and are the cells best able to engraft tumors in mouse models.  My work seeks to better understand their characteristics to identify vulnerabilities that could be targeted clinically to improve patient survival.  Currently, I am focusing on their cellular metabolism.  Quiescent cells have long been thought to be metabolically silent.  However, recent data indicates that their metabolism is active but reprogramed compared to proliferative cells.  Quiescent cell metabolism is also distinct from another nonproliferative cell type: senescent cells.  Senescence is a form of stable cell cycle arrest also important in ovarian cancer that has its own distinct metabolic reprogramming relative to proliferative cells.  Better understanding the metabolism of both quiescent and senescent ovarian cancer cells could reveal insight into the regulation of these two important programs for growth arrest and potentially reveal novel therapeutic approaches for treating ovarian cancer.

In addition to the crucial insight we can gain from studying the cancerous cells within a tumor, it is important to also consider the influence of noncancerous host cells within the tumor and how they can impact treatment failure.  As such, my second project examines the interaction between these quiescent, chemoresistant ovarian cancer cells and components of the host tumor immune microenvironment, particularly tumor-associated macrophages.  Disrupting the supportive interactions between tumor-associated macrophages and chemoresistant ovarian cancer cells could potentially improve chemotherapy effectiveness and reduce relapse.