Don Powell, MD
Director, Division of Gastroenterology and Hepatology;
Program Director, General Clinical Research Center;
Professor, Internal Medicine; Professor,
Neuroscience and Cell Biology
NIH Biosketch (none available)
Dr. Powell has been awarded NIH funding for over 40years to study mechanisms of intestinal electrolyte transport and, at present, his interest has turned to the immune system control of these processes, COX-2 gene regulation, immunology of mesenchymal cells and colon cancer microenvironment.
Research in the lab focuses upon the biology of intestinal myofibroblasts (IMF). These cells are members of a family of phenotypically-related cells that include glomerular mesangial cells, renal and pulmonary interstitial fibroblasts and hepatic and pancreatic stellate cells. Located at the interface between the epithelium and lamina propria, IMF modulate information transfer between these tissue compartments and play a pivotal role in immunology, physiology, development, and carcinogenesis of the gastrointestinal tract. These cells are likely to play an important role in the etiology of colon cancer, inflammatory bowel disease (IBD) and immune tolerance. Ongoing projects involve:
1. Regulation of cyclooxygenase-2 (COX-2) gene expression in IMFs. This NIH funded research combines biochemical, molecular biological, and histochemical approaches to understand signaling pathways that regulate COX-2 in IMFs. This research is significant since COX-2 expression is observed in IMF during the early stages of colorectal carcinogenesis and the chemopreventive effects of nonsteroidal anti-inflammatory drugs derive from their ability to inhibit synthesis of COX-derived prostaglandins.
2. IMF as novel immune regulators. This research combines immunological, molecular biological, and histochemical approaches to understand how IMF interact with immune cells to modulate intestinal inflammation and possibly tolerance to dietary and bacterial antigens present in the intestinal lumen. In collaboration with the laboratory of Dr. Victor Reyes (Microbiology and Immunology), experiments are being conducted to characterize class II MHC-mediated antigen presentation by IMF and the ability of antigen presenting IMF to either stimulate a T cell mediated immune response, or to promote antigenic tolerance or anergy. Knowledge derived from these studies will be used to determine defects associated with IMF in IBD and celiac disease.
3. IMFs form the stem cell niche for the intestinal epithelium by secreting factors (Wnts, BMPs, various antagonists) and matrix molecules that control stem cell growth. Their role in development and colon cancer is a new area of research in this laboratory.