Grant: Project Grant

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is accompanied by high levels of signaling molecules called pro-inflammatory cytokines. These cytokines play a critical role in mediating IBD by causing the lining of the intestinal tract to become dysfunctional. This inflammation is believed to be an inappropriate reaction to normal inflammatory signals, and may be triggered by interactions of cells in the intestine with resident bacteria in combination with factors that pre-dispose individuals to IBD. Inflammatory signaling pathway are subject to complex regulation by many different factors. We are focused in the role of a transcription factor called CDX2 in this process. CDX2 regulates the expression of target genes, thereby altering the protein composition of cells and changing the way the cells function. CDX2 is, in fact, essential to the normal operation of our intestinal tract. This was demonstrated by our group and others who have shown that mice engineered to lack CDX2 completely lose normal intestinal function. In addition to these critical cellular processes in the intestine, there is increasing evidence linking CDX2 to IBD. The objective of our work is to better understand how CDX2 impacts processes related to IBD using our preclinical mouse model in which we can eliminate CDX2 function in the intestine. Results forthcoming from these studies are anticipated to shed new light on the causes of IBD in patients and to identify potential new means for the treatment of these diseases.