Grant: Operating Grant

The intestine is lined with a single layer of epithelial cells that ensure nutrient uptake. Because of the hostile environment in which they are found these cells are replenished rapidly and continuously throughout our lifetime. A stem cell population, located in the lower regions of the glands, divides constantly producing the required cells. The use of genetic mouse models has identified a host of signals mediating changes that these cells must undergo in order to go from immature cells to fully functional cells. When these signals or processes go awry cells no longer receive the correct instructions leading to different pathological conditions, such as cancer. In comparison, little is known about how these functions in man. In the current grant we propose to study the cellular and molecular mechanisms than regulate stem cells and cell organization in the glands. We have developed a special normal intestinal cell line that behaves as a stem cell allowing us to manipulate their environment and directly study how these cells react. Better understanding of the cellular organization in the human intestinal crypt would significantly impact many fields related to gastroenterology namely intestinal stem cell biology, tissue repair and carcinogenesis, in addition to the potential therapeutic use that these cells may offer in the near future.