In the gut, a special class of immune cells called intestinal intraepithelial lymphocytes (IELs) act as frontline defenders against infection and inflammation. When these cells don’t function properly, it can lead to serious diseases like inflammatory bowel disease (IBD) and colorectal cancer. In this project, Dr. Zachary Earley will investigate how IELs develop, migrate, and become “long lived” to maintain gut-immune balance – and the Gα13/GPR132 signaling pathway may be the key.
The Gα13/GPR132 signaling pathway allows cells to sense and respond to environmental signals. Without Gα13, IELs fail to survive in the gut, though they remain healthy elsewhere in the body, making it a unique marker to use for manipulations. Dr. Earley hypothesizes that blocking this pathway may actually protect against gut inflammation, pointing to a possible new treatment for intestinal autoimmune diseases. “Understanding how these diseases develop and finding novel approaches to treat them is what motivates me to pursue a career in science,” Dr. Earley says. In his doctoral work at the University of Chicago, he uncovered how intestinal epithelial cells – cells that line the inside of the intestines – regulate microbial colonization and influence inflammation in diseases like celiac disease. He also revealed how an antibody called IgA maintains immune homeostasis and controls the microbiota. Now, Dr. Earley is focused on uncovering tissue-specific immune signaling pathways, like Gα13, that may hold the key to treating chronic intestinal diseases without systemic immune suppression.
Sponsor
Jason Cyster, PhD
Research Focus
Inflammatory bowel disease, colorectal cancer, gut-immune balance
Projects and Grants
Gα13 signaling in intestinal epithelial lymphocyte homeostasis
