Project Grant R01DK145577

The National Institute of Diabetes and Digestive and Kidney Diseases awarded $814,500 to the University of Pittsburgh on September 1, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to fund research dissecting functional decompensation of end-stage liver disease and investigating the mechanism and impact of transcription factors on long-term functional reprogramming.

The research examines how the transcription factor HNF4A—which controls metabolic, detoxification, and synthetic pathways critical for hepatocyte function—becomes dysregulated in end-stage liver disease and cirrhosis. Prior work demonstrated that re-expression of HNF4A mRNA alleviates transcriptomic changes associated with hepatic failure and improves liver function and survival in vivo; however, the mechanisms by which end-stage liver disease progresses and how HNF4A reprogramming successfully alleviates decompensated cirrhosis and hepatic failure remain unknown. The project seeks to identify potential therapeutic targets for pharmacological intervention in end-stage liver disease, which causes approximately 300,000 deaths annually in the United States.

Work is performed in Pittsburgh, Pennsylvania. The period of performance runs from September 1, 2026, through June 30, 2030.