Colorectal cancer (CRC) is a significant health problem in the United States and around the world, affecting almost two million people—and being responsible for almost one million deaths—each year. One of the key risk factors of developing CRC is inflammatory bowel diseases (IBDs), such as Crohn’s disease and ulcerative colitis. Nearly 20 percent of IBD patients are estimated to develop CRC within thirty years of disease onset. The intestinal nervous system, sometimes called our “second brain”, has been found to play critical roles in regulating inflammation in the gut, but little is understood about the pathways involved.
Previously, Dr. Mowel and his team have shown that the gut nervous system promotes defense against bacterial infection through inflammasomes. While these inflammasomes have been closely linked to development of IBD, the role of gut neurons in this process is unclear, so Dr. Mowel plans to examine the role of the intestinal nervous system in IBD by disabling inflammasomes in these cells. He is also determining the subpopulations of gut neurons that produce inflammasomes and the signals that activate them. Due to the connection between IBD and CRC, clarifying how the gut nervous system regulates inflammation during IBD may reveal key mechanisms that can be therapeutically targeted to address colitis and prevent the development of colorectal cancers.
Projects and Grants
The role of enteric nervous system-derived IL-18 in intestinal inflammation and cancer
Yale University | Colorectal Cancer, Stomach Cancer | 2020 | Richard A. Flavell, Ph.D.
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