The major research focus of the Center for Inflammatory Bowel Diseases continues to be the expansion of existing knowledge to better understand the role of neuropeptides in the development of the intestinal inflammatory response and IBD pathophysiology.
The goal of this project is to study the extent of abdominal fat tissue involvement in the generation of inflammation during inflammatory bowel disease (IBD). In this research, we found that fat cells respond to pro-inflammatory stimuli (such as the neuropeptide substance P), shown to be present during IBD, and in turn are able to produce inflammatory cytokines themselves. Such cytokines have also been shown to be involved in IBD pathophysiology. We hope to ultimately achieve additional results through our research and demonstrate whether fat cells actively participate in the events taking place in the colonic lumen during IBD.
This project focuses on the neuropeptides Substance P and neurotensin and their effects on colon cancer susceptibility in chemical carcinogenesis and orthotopic xengraft mouse models. Recent findings indicate that pharmacologic or genetic disruption of either the Substance P or neurotensin pathways reduce colon cancer development at early stages. Ongoing studies are aimed at addressing the interactions of these pathways with other known pathways that regulate cancer development, and whether manipulation of signaling has an effect on the later stages of invasion and metastasis.
The goal of this project is to define a role of angiogenesis in the gut physiology and pathology, and finding new regulators of angiogenesis and underlying mechanism of action. Specifically, we have investigated the function of the corticotropin releasing hormone (CRH) family of peptides as a novel angiogenic regulator in intestinal inflammation. The CRH family of peptides binds to two G protein coupled receptors, CRHR1 and CRHR2, to exert its biological activity. Recently, we observed the differential immunomodulatory effect of CRHR1 and CRHR2 in animal studies and the opposite angiogenic effect of both receptors from in vitro and in vivo studies. Studies to be presented will include an overview of the function of the CRH family peptides in the gut pathophysiology including IBD, a role of two different CRH receptors in intestinal angiogenesis and inflammation, and their putative mechanism of action.
The goal of this project is to study the role of anti-microbial peptide cathelicidin in intestinal inflammation and cancer. Specifically, we study the molecular mechanism of cathelicidin synthesis in colons and its immunomodulatory roles of cathelicidin in acute and chronic colitis.