The principal investigator for this proposal, Dr. Taylor, is a NRSA- funded post-doctoral fellow at Brigham and Women's Hospital and Harvard Medical School. Work outlined in this proposal will serve to fund the mentored transition of Dr. Taylor from a post-doctoral fellow to an independent academic investigator and application for R-01 level funding. The mentor for this proposal, Dr. Colgan is an independent scientist with extensive published experience in the areas of epithelial and endothelial cell biology. A mentor committee consisting of Dr. Colgan and three other senior scientists (Dr. Serhan and Dr. Blumberg and Dr. Stahl) will serve as an advisory committee for Dr. Taylor and will carefully oversee his progress. The environment in which the proposed work will be carried out (Harvard Medical School) is a world class scientific community where biomedical research is performed at the highest level with intimate associations between clinical and basic science disciplines. In this proposal we will investigate the role of cAMP responsive genes in mediating epithelial responses to hypoxia. Tissue hypoxia is associated with a number of chronic inflammatory conditions in the intestine. Alterations in intestinal epithelial phenotype are associated with the pathophysiology of such inflammatory disease. We have previously demonstrated a role for hypoxia in the transformation of epithelial cells to a phenotype associated with mucosal inflammation. At present, little is known about the molecular events associated with epithelial responses to hypoxia. As work in progress, we have identified an important role for cAMP-responsive genes in mediating epithelial responses to hypoxia. The overall goal of this proposal is to investigate the mechanism of hypoxia-elicited induction of cAMP-responsive genes in mediating epithelial responses to hypoxia. The overall goal of this proposal is to investigate the mechanism of hypoxia-elicited induction of cAMP responsive gene expression and to define the impact of such events on intestinal epithelial function.
| Comerford, Katrina M; Leonard, Martin O; Karhausen, Jorn et al. (2003) Small ubiquitin-related modifier-1 modification mediates resolution of CREB-dependent responses to hypoxia. Proc Natl Acad Sci U S A 100:986-91 |
| Colgan, Sean P; Taylor, Cormac T; Narravula, Sailaja et al. (2002) Endothelial COX-2 induction by hypoxia liberates 6-keto-PGF1 alpha, a potent epithelial secretagogue. Adv Exp Med Biol 507:107-12 |
| Furuta, G T; Turner, J R; Taylor, C T et al. (2001) Hypoxia-inducible factor 1-dependent induction of intestinal trefoil factor protects barrier function during hypoxia. J Exp Med 193:1027-34 |
| Taylor, C T; Colgan, S P (1999) Therapeutic targets for hypoxia-elicited pathways. Pharm Res 16:1498-505 |
