Nicholas O. Davidson, M.D. (Director)

DEPARTMENT OF Int Med - Gastroenterology
Jeffrey I. Gordon, M.D.; Gregory A. Grant, Ph.D.; Kevin A. Roth, M.D., Ph.D.; William F. Stenson, M.D.
Keywords: intestine, liver, gene expression

This program project examines the function and biology of proteins in gastrointestinal tissues at the cellular and molecular level. Under study are several genes and their protein products expressed in cells of foregut origin (chief and parietal cells of stomach, salivary acini and ducts), in enterocytes and in hepatocytes. Gene products studied include cobalamin binding proteins (intrinsic factor and transcobalamin), liver and intestinal fatty acid binding proteins, Na, K-ATPase and long chain acyl CoA dehydrogenase. Different aspects of the same proteins are studied by multidisciplinary teams in an integrated approach.

The regulation of gene expression in epithelial cells of the gastrointestinal tract and the relationship between structure and function of certain gastrointestinal proteins are two of the project’s major thrusts. Gene expression is studied by analyzing transcriptional regulation and the response to environmental factors. These include dietary and hormonal stimuli. The project also involves studies of the structure and function of cobalamin binding proteins and long chain acyl CoA dehydrogenase. The project uses molecular and cell biology techniques and runs core facilities in biomolecular analysis, morphology, and cell culture employing HPLC (for peptide separations), protein sequencers, oligodeoxynucleotide synthesizers, cell culture of intestinal and pancreatic cell lines, light and electron microscopy, computer assisted morphometric analyses, immune localization and in situ hybridization. The project uses model systems to provide insights into: 1) synthesis and processing of cellular and secreted gastrointestinal proteins; 2) molecular mechanisms of cellular differentiation and adaptation; 3) relationship between structure and function of specific gut proteins; and 4) biochemical changes related to three human problems, drug delivery (via cobalamin binding proteins), Helicobacter pylori infection and long chain acyl CoA dehydrogenase deficiency.