Intestinal Stem Cells and Disease
The intestine is critical in numerous disorders of significant public health concern, including diabetes, inflammatory bowel disease, and colon cancer. The innermost lining of the intestine, called the epithelium, is responsible for nutrient absorption. It contributes to the body's energy balance and interacts with a rich collection of gut microbes that help shape overall intestinal and metabolic health. The intestinal epithelium is home to several types of specialized cells that are the most rapidly renewing in the entire body. Remarkably, in order for the intestine to function properly, it needs to renew the epithelial lining every three to five days.
This rate of renewal is driven by adult intestinal stem cells (ISCs). Despite their importance and recent advances in technology to capture and study ISCs, there are many unanswered questions about how ISCs respond to dietary and microbial cues in order to maintain proper function. The molecular mishaps that lead to defects in ISC function—which can substantially elevate the risk of many disorders including diabetes—remain poorly characterized.
With this highly competitive Pathway (to Stop Diabetes) Accelerator Award, Praveen Sethupathy, Biomedical Sciences, and his team are uncovering the master regulators of ISC gene expression and function—a class of biomolecules called microRNAs—particularly in response to dietary modification and microbial imbalance. MicroRNAs have emerged as candidate therapeutic targets for a broad spectrum of diseases and could provide new therapeutic avenues for intestinal disorders. Sethupathy is working toward this outcome, while advancing understanding of intestinal function at the molecular level and providing new insight into the role of intestinal microRNAs in metabolic disease.
American Diabetes Association Grant Number: 1-16-ACE-047