Gastroenterology and Gut Health
I have a long-standing interest in the regulation of cell death in intestinal epithelial cells. Recently I have become interested intestinal epithelial cell shedding, a special form of cell death which arises as a consequence of the high flux of epithelial cell which arise from stem cells at the base of crypts and migrate up to the villi in the case of the small intestine or intestinal surface in the case of the colon. When a cell is shed a discontinuity is created in the epithelial monolayer that has been named a “gap”. Under normal conditions the “gap” is short lived and barrier function is maintained at sites of cell shedding. However, during inflammation cell shedding is increased and can become confluent leading to the formation of micro-ulcers. Barrier function is also sometimes lost during inflammation, creating sites for the potential entry of microorganisms and luminal antigens. This work focuses on mouse models and multiphoton microscopy and imaging of cell shedding in humans by confocal endomicroscopy.