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Immune interactions at the intestinal epithelium
Inflammatory bowel diseases (IBD) and colon cancer are both diseases involving the intestinal epithelium, the single layer of epithelial cells that serves dual functions of nutrient absorption and protection from the external environment. The epithelial layer also contains a complex and unconventional pool of T cells collectively called intraepithelial lymphocytes (IEL). These IEL patrol the epithelial layer, and are tasked with eliminating infected, damaged or transformed epithelial cells. IEL are required for regulating the viral, bacterial, and parasite loads in the gut, and are even capable of preventing infection completely (Swamy et al., 2010, 2015). Despite their importance, we understand very little of how these cells are activated, or their mechanisms of action.
Research in my lab focuses on the fundamental roles of IEL in coordinating responses to chemical, dietary and microbial inputs, either directly, or indirectly through intestinal epithelial cells. Our group studies the signaling pathways that activate intestinal IEL to mediate epithelial cell death and/or repair. We use a combination of biochemistry, proteomics, transgenic mouse models, and in vivo infection studies.
In recent work, we have measured and quantified the complete proteomes of primary intestinal epithelial cells and IEL using high resolution mass-spectrometry. We are using these data to identify and characterize molecular interactions between IEL and intestinal epithelial cells. Ultimately, we hope to have a better understanding of how IEL contribute to intestinal homeostasis in health and disease.
