Grant: Project Grant

The mucus bilayer in the colon is the first line of host defense by forming a protective shield against pathogen invasion of the underlying single layer of epithelial cells while supporting a health microbiota to maintain homeostasis. Critical to innate defense, constitutive and induced mucus secretion by goblet cells is tightly regulated by a variety of proteins that make up the machinery within the cell. At present, it is not known how mucus secretion in the gut is regulation by the protein secretion complex in goblet cells. In this study our goal is to identify the protein binding partners that interact in goblet cells to control mucus secretion basally and in response to chemical induced colitis and pathogen stimulation that enhance mucus secretion to protect the epithelium from damage. We will extent the study to quantify if defects in the mucus secretion machinery exists in inflammatory bowel disease (IBD). In IBD, mucus is severely altered that predisposes the gut to pathogen damage. A major goal in IBD treatment is mucosal healing where mucus is at the center stage in this process. Our studies will define a mechanistic role on how mucus secretion is defective that will inform us on new treatment regimes in treating IBD and infectious colitis.