The Zhou lab is focused on identifying critical factors that orchestrate the regeneration of pancreatic insulin-secreting beta cells and intestine stem cells. Based on principles of development, we identified master regulators that dictate the formation of beta-cells and intestine stem cells during embryogenesis and by modulating the expression of these master genes, one can remake, or reprogram existing adult cells from one type to another, thereby regenerating medically important cell types.
On beta-cell regeneration, we have identified a cocktail of three pancreatic master regulators that can reprogram murine gut epithelial cells to insulin-secreting cells capable of regulating blood sugar levels. Current focus is to derive insulin-secreting cells from cultured human gut stem cells as a potential transplantation therapy for diabetes, and to use the gut-derived insulin+ cells to model Type 1 diabetes, an autoimmune disease.
On intestine regeneration, we recently identified master regulators that distinguish the large intestine from the small intestine. Modulating expression of these factors in gut stem cells leads to rapid reprogramming from large intestine epithelium to small intestine epithelium and vice versa. We are interested in understanding how the gut master regulators maintain large intestine identity, and in evaluating the importance of these factors in short-bowel disease and inflammatory bowel diseases.