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Mitchell B. Cohen, MDProfessor and Director of Gastroenterology, Hepatology and Nutrition Associate Director, Digestive Health CenterVice-Chair of Pediatrics for Clinical Affairs Department of Pediatrics; Division of Gastroenterology, Hepatology and NutritionVisit the Cohen/Steinbrecher Lab
Dr. Cohen studies host-pathogen interactions and intestinal secretion. His current work is investigating the physiologic roles of the E. coli heat stable enterotoxin receptor, guanylyl cyclase-C (GC-C). This receptor also binds the endogenous mammalian peptides, guanylin and uroguanylin, that are produced in the intestine. Recent work in mice and humans suggests a role for transmembrane GC-Cs in intestinal fluid secretion as well as hormonal enteric-renal signaling that mediates postprandial natriuresis. Dr. Cohen has generated two knockout strains of mice, one with a deletion of the guanylin gene and the other with a deletion of the uroguanylin gene. He is using these mice as well as GC-C knockout mice to test the hypotheses that guanylin and uroguanylin signaling plays a protective role in the integrity of the intestinal mucosal barrier. In addition, he is testing the hypothesis that these peptides demonstrate a novel and critical role for this receptor-ligand system in the pathogenesis of mucosal inflammation. Studies in humans are investigating the safety, immunogenicity and protective efficacy of novel vaccines against important diarrheal pathogens, including enterotoxigenic E. coli and V. cholerae.
Dr. Cohen has used the Bioinformatics, Gene and Protein Expression, and Integrative Morphology Cores in collaboration with Drs. Aronow, Han, Shull, Steinbrecher, and Witte to study the role of the guanylin/uroguanylin/GC-C circuit and of other intestinal peptides on secretory mechanisms in the intestinal tract. He has also used the same core services in collaboration with Dr. Rothenberg on studies investigating pathogenic mechanisms of pro-inflammatory and eosinophilic gastrointestinal disorders.
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In panel C, TUNEL analysis demonstrates increased levels of apoptosis in uroguanylin knockout mice (UGN; ligand for the GC-C receptor) compared to wild type (WT) following exposure to radiation (5 Gy). Similar results were seen in the intestine of GC-C knockout mice (panel D). Figure from Am J Physiol 2009; 296: G740-G749.
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