Expertise in Gut Barrier Dysfunction Earns UTHSC Researcher Two Awards Totaling $5 Million

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Radhakrishna Rao, PhD, vice-chair and professor in the Department of Physiology at the University of Tennessee Health Science Center (UTHSC), has received two large national awards totaling $5 million for separate studies involving the gut as a therapeutic target for treating disease. Dr. Rao is known worldwide for his two decades of research into the structure and regulation of the intestinal epithelium, which forms the gut barrier preventing allergens, toxins, and pathogens from entering the bloodstream.

Dr. Radhakrishna Rao

This month, the National Institute of Allergy and Infectious Disease awarded Dr. Rao $2.5 million to study how acute radiation syndrome affects the gut microbiome and intestinal mucosal barrier function. Public exposure to radiation due to large-scale incidents is a rising global concern. The gastrointestinal tract is one of the first organs injured by radiation, but no FDA-approved treatments exist for gastrointestinal acute radiation syndrome.

Dr. Rao and his team will work to determine how radiation alters innate intestinal immunity by suppressing antibacterial peptide production in the gut. They also aim to identify how supplementing such peptides can prevent and treat radiation injury. This project will test and develop a new FDA-regulated drug that can be used in the event of radiation exposure to the public.

“I believe the gut is a critical target for treating many diseases, including acute radiation syndrome,” Dr. Rao said. “Therefore, it is exciting to have this unique opportunity to explore intestinal Paneth cell-based innate immunity as a novel therapeutic target for developing a treatment strategy to treat acute radiation syndrome.”

Earlier this year, the National Institute on Alcohol Abuse and Alcoholism awarded Dr. Rao $2.5 million for a project to identify therapeutic targets to develop drugs to treat alcohol-associated diseases. Dr. Rao and his collaborators have identified certain calcium channels (TRPV6 and CaV1.3) in the intestinal epithelium that drive alcohol-induced endotoxemia and systemic inflammation by enforcing intestinal epithelial junction disruption and mucosal barrier dysfunction. The project will test how the coordinated activities of those channels mediate an alcohol-induced rise in epithelial cellular calcium leading to gut permeability and systemic inflammation. It will also evaluate the potential of calcium channel blockers to mitigate and prevent alcohol-induced endotoxemia and liver damage.

“Once again, the intestine is the crucial therapeutic target for alcohol-associated liver disease,” Dr. Rao said. “I have no doubt that more evidence will emerge supporting the gut as the primary therapeutic target for many systemic diseases. Science is accomplished best by multidisciplinary approaches. I am fortunate to have a team of collaborators with expertise in diverse discipline.”

Dr. Rao is also a recent awardee of the Veterans Health Administration Merit Review Award to study the impact of chronic stress on alcohol-induced tissue injury at the gut-liver-brain axis.