BME Seminar Series: Dr. Gina M. Sizemore, The Ohio State University

Abstract:

"The tumor microenvironment in breast cancer initiation, growth

and metastasis”

Breast tumors are surrounded by and in contact with many types of non-cancer cells including fibroblasts, pericytes, immune cells and adipocytes. These surrounding cells are collectively termed the “tumor microenvironment” (TME), and the interplay between tumor cells with these nearby non-tumor cells greatly affects all steps of cancer progression. Research in the Sizemore lab focuses on novel factors in both the primary breast TME and in the metastatic microenvironment that we predict could be utilized as biomarkers/therapeutic targets to more effectively treat patients with breast cancer. In searching for driver pro-metastatic pathways, our analyses uncovered a receptor tyrosine kinase, platelet derived growth factor receptor-beta (PDGFRβ), that we believe functions in the initiation and/or growth of breast cancer brain metastases. PDGFRβ is found primarily in cells of the breast tumor/metastatic microenvironment while its ligand, PDGF-B, is expressed primarily by the breast tumor cells. Importantly, breast cancer brain metastases arise in ~10-20% of all metastatic breast cancer patients, and due to the complete lack of approved treatments for these patients, only one fifth will still be living one year after their diagnosis. Our current work aims to address this important clinical problem through use of both in vitro cell line and in vivo mouse modeling of PDGF-B to PDGFRβ signaling in the TME. Additional projects in the lab focus on PDGFRβ and other stromal factors in normal mammary gland development.

Bio:

I am currently a full-time, tenure-track Assistant Professor in the Department of Radiation Oncology at The Ohio State University-James Comprehensive Cancer Center. My complete body of work has focused on delineating the key molecular drivers that maintain the breast cancer subtype-specific phenotypes and, more recently; this focus has expanded to incorporate pro-tumorigenic and pro-metastatic elements of the tumor microenvironment (TME). In addition to these research interests, my doctorate degree in Pharmacology provided me with the tools necessary to conduct research designed to identify novel therapeutic targets for any disease type. This proposal focuses on defining the molecular/cellular mechanism behind why breastfeeding is protective against triple negative breast cancer. Defining this mechanism could significantly impact lifestyle choices in women predisposed to this disease, in particular in the African American population, as well as identify potential therapeutic targets for women who are unable to breastfeed for a variety of reasons. As a co-investigator on this application, I have been intimately involved in this research project from conception (method development, preliminary studies, result interpretation). In order to complete the experiments outlined in this proposal, I will continue to provide my extensive expertise in the generation and utilization of transgenic/knockout mouse models of mammary gland development and breast cancer, mammary stem/progenitor cells, transcriptomics and mechanisms of transcriptional control. Of note, I have published under my maiden name of Gina M. Bernardo.