William Stenson, M.D.

DEPARTMENT OF Internal Medicine
Keywords: inflammation, epithelium, cyclooxygenase, lipids, cancer, cell biology

We have two major areas of interest in our lab. The first is the regulation of the intestinal epithelial response to injury. The intestinal epithelium responds to injury in a stereotyped fashion with apoptosis, alterations in the cell cycle and changes in the rate of proliferation. We study the epithelial response to injury using radiation models and chemical injury models. The radiation injury models include whole body radiation in mice and the radiation of human intestinal colon cancer cell lines. We also use two models of chemically induced colitis: dextran sodium sulfate induced colitis and trinitro- benzenesulfonic acid induced colitis in mice. A major thrust of our studies has been an investigation of the modulation of the intestinal response to injury by both endogenous and exogeneous prostaglandins. We have found that prostaglandins decrease radiation-induced apoptosis, shorten the period of radiation-induced cell cycle arrest and promote stem cell survival. Recently, in collaboration with Thaddeus Stappenbeck from the Department of Pathology, we have demonstrated that there is a population of prostaglandin secreting stromal cells in the intestine that migrate to an area adjacent to the proliferating epithelial cells in response to injury and that migration is mediated through a toll-like receptor dependent mechanism. The second major area of interest in our laboratory is mucosal immunology in the intestine and in particular the role of indoleamine- 2,3-dioxygenase in regulating intestinal inflammation. We have found that indoleamine 2,3-dioxygenase is a naturally occurring brake on intestinal inflammation and that inhibition of this enzyme results in worsening of intestinal inflammation. We are in the process of determining if agents that induce the expression of indoleamine-2,3-dioxygenase such as CTLA4-Ig or CpG are useful as drugs in the regulation of intestinal inflammation.