Seminar: Graduate Research Proposal Presentation (Stephanie Totilo)

Endocrinology and Animal Biosciences Seminar: 

Graduate Research Proposal Presentation

Stephanie Totilo
PhD Student

Breast cancer is the most common cancer among women in the United States. Both modifiable and nonmodifiable factors, including alcohol consumption influence breast cancer risk. Timing and duration of alcohol exposure can impact this risk. The Developmental Origins of Health and Disease (DOHaD) hypothesis states that early-life exposures, such as prenatal alcohol exposure (PAE), can predispose individuals to disease later in life, potentially through epigenetic mechanisms. Our laboratory has shown PAE decreases tumor latency in the MMTV-Wnt1 (Wnt) model for basal-like breast cancer. Recently, single cell transcriptomic analysis has indicated that PAE induces a pro-inflammatory tumor microenvironment, including increased chemokine expression. Aim 1 of this proposal will further investigate this finding, specifically determining whether PAE inhibits LSD1 activity in mammary tumors leading to increased CCL5 expression and determining if this occurs through an epigenetic mechanism. According to the DOHaD hypothesis, PAE may induce changes early in development which could lead to increased risk in adulthood. The second specific aim will determine if this occurs by using scRNA-seq analysis to look at the cellular composition and transcriptome of preneoplastic Wnt mammary glands with a focus on identifying epigenetic regulators that may be altered. Together, these studies provide further insight into the mechanisms by which PAE affects mammary gland development and subsequent tumorigenesis, advancing our understanding of the developmental origins of breast cancer risk.