The role of the MTG family and BVES in intestinal biology and tumorigenesis

Abstract

Intestinal homeostasis relies on complex interactions between the intestinal epithelium, microbiota, and host immune system, all of which cooperate to maintain homeostasis in an environment colonized and challenged by an estimated 100 trillion bacteria. It is the disruption and dysregulation of these interactions that is currently thought to underlie intestinal pathologies such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). The Myeloid translocation gene (MTG) family of transcriptional corepressors and the tight-junction associated protein Blood vessel epicardial substance (BVES) have been shown to be important regulators of the intestinal epithelium. I hypothesized that loss of MTG or BVES function play important roles in IBD and CRC. Using genetic mouse models, cell lines, and organoid cultures, we clarified the role MTGs and BVES play in intestinal pathologies by identifying their binding partners and what signaling pathways they regulate. Overall, the primary objective of my work was to further elucidate the functional role of MTGs and BVES in the intestinal epithelium and carcinogenesis.