Dr. Whang, an Instructor in Surgery at Harvard Medical School, aspires to become an independent investigator, working at the interfaces between clinical and basic sciences as he seeks new therapies for gastrointestinal disorders. The long-term goal of this proposal is to develop new strategies for treating patients suffering from the short bowel syndrome. Chronic total parenteral nutrition and intestinal transplantation are currently the only available options for these patients; new approaches are desperately needed. The hypotheses underlying these studies are 1) specific cell cycle regulatory mechanisms mediate intestinal regeneration that occurs during adaptation following massive small bowel resection and 2) an understanding of these mechanisms can be exploited to rationally design methods to maximally augment the regenerative response.
Three specific aims will address these hypotheses. The first two aims are to characterize the cell cycle regulatory mechanisms in intestinal regeneration using 1) a reductionist in vitro model and 2) a wild-type and genetically-altered mice lacking specific cell cycle regulators.
The third aim i s to design and deploy a therapeutic """"""""cocktail"""""""" that maximally stimulates intestinal regeneration. During he five-year period of this award, Dr. Whang will acquire expertise with the concepts and methods of studying cell cycle regulation in the gastrointestinal tract. Collaborative mentorship from both a surgical investigation and a basic scientific will allow this young surgeon to obtain the skills necessary to become an independent investigator.
| Perez, Alexander; Duxbury, Mark; Rocha, Flavio G et al. (2005) Glucagon-like peptide 2 is an endogenous mediator of postresection intestinal adaptation. JPEN J Parenter Enteral Nutr 29:97-101 |
| Rocha, Flavio G; Shen, K Robert; Jasleen, Jasleen et al. (2004) Glucagon-like peptide-2: divergent signaling pathways. J Surg Res 121:5-12 |
| Ramsanahie, Anthony P; Berger, Urs V; Zinner, Michael J et al. (2004) Effect of glucagon-like peptide-2 (GLP-2) on diurnal SGLT1 expression. Dig Dis Sci 49:1731-7 |
| Tavakkolizadeh, Ali; Berger, Urs V; Stephen, Antonia E et al. (2003) Tissue-engineered neomucosa: morphology, enterocyte dynamics, and SGLT1 expression topography. Transplantation 75:181-5 |
| Ramsanahie, Anthony; Duxbury, Mark S; Grikscheit, Tracy C et al. (2003) Effect of GLP-2 on mucosal morphology and SGLT1 expression in tissue-engineered neointestine. Am J Physiol Gastrointest Liver Physiol 285:G1345-52 |
| Duxbury, Mark S; Waseem, Talat; Ito, Hiromichi et al. (2003) Ghrelin promotes pancreatic adenocarcinoma cellular proliferation and invasiveness. Biochem Biophys Res Commun 309:464-8 |
| Perez, Alexander; Grikscheit, Tracy C; Blumberg, Richard S et al. (2002) Tissue-engineered small intestine: ontogeny of the immune system. Transplantation 74:619-23 |
| Ramsanahie, Anthony P; Perez, Alexander; Duensing, Anette U et al. (2002) Glucagon-like peptide 2 enhances intestinal epithelial restitution. J Surg Res 107:44-9 |
| Jasleen, Jasleen; Ashley, Stanley W; Shimoda, Naoshi et al. (2002) Glucagon-like peptide 2 stimulates intestinal epithelial proliferation in vitro. Dig Dis Sci 47:1135-40 |
