Project Grant R01AA033346

The National Institute on Alcohol Abuse and Alcoholism awarded The University of Texas Southwestern Medical Center $702,746 on September 1, 2026, under the Alcohol Research Programs (CFDA 93.273) to investigate epigenetic regulation of endogenous retroviruses and alcohol-associated liver disease.

The research will define mechanisms by which alcohol metabolism induces endogenous retrovirus (ERV) reactivation, reverse transcription, and innate immune activation, focusing on metabolic and epigenetic regulation. Using complementary murine models, ethanol-metabolizing VL-17A cells, and human liver organoids, the recipient will dissect how ERV-derived nucleic acids contribute to alcohol-induced injury and test whether targeting reverse transcription represents a viable therapeutic strategy. Preliminary data show that alcohol-induced reductive stress reactivates ERVs and that reverse transcriptase inhibitors reduce alcohol-induced liver injury, steatosis, and inflammation in mice; retrospective clinical data indicate that patients on reverse transcriptase inhibitors have lower rates of alcoholic hepatitis, cirrhosis, and adverse liver outcomes. The work will establish ERV reactivation as a driver of alcohol-associated liver disease and alcoholic hepatitis, and evaluate FDA-approved reverse transcriptase inhibitors as potential mechanism-based therapies.

Work is performed in Dallas, Texas. The project period runs through May 31, 2031.