Dr. Shivdasani’s laboratory investigates molecular mechanisms of cell differentiation and tissue-specific gene regulation in the developing and adult gastrointestinal tract. One core effort aims to elucidate and characterize genetic pathways and epigenetic control mechanisms that regulate progressive differentiation of embryonic endoderm into gut epithelial progenitors and, finally, into self-renewing digestive epithelia. A second core effort investigates the roles of adult tissue-restricted transcription factors in responding to extra-epithelial signals and underlying chromatin states with specific transcriptional outputs. These research activities share the use of paradigms in cell differentiation and relevance to human disease, particularly cancer. The laboratory has made valuable contributions toward current understanding of mammalian gut development, patterning of digestive organs, adult intestinal stem cells, and the roles of chromatin modifying enzymes such as Polycomb Repressive Complex 2 in tissue-specific gene control. Powerful in vivo and ex vivo experimental models are applied to identify fundamental control mechanisms that might explain malignant cell behaviors.