Federal Grant Award Summary

Cincinnati Children's Hospital Medical Center received a $851,275 Project Grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), awarded February 15, 2026, with completion targeted for December 31, 2029. The grant supports fundamental research into the mechanisms regulating hepatocyte plasticity and hepatocyte-to-cholangiocyte reprogramming to address intrahepatic bile duct (IHBD) paucity, a significant cause of pediatric liver disease associated with conditions including Alagille Syndrome, Progressive Familial Intrahepatic Cholestasis, and biliary atresia.

The research deliverables include investigations of how Notch signaling thresholds and temporal factors influence zonation-specific hepatocyte reprogramming sensitivity, and characterization of PRDM16's role as a histone methyltransferase in regulating chromatin accessibility and facilitating hepatocyte-to-cholangiocyte conversion. Using integrated human-mouse datasets spanning infancy through adulthood, researchers will generate scientific findings and methodological insights aimed at developing potential therapeutic interventions to augment IHBD architecture and reduce the need for liver transplantation in pediatric patients. The research combines cutting-edge molecular and chromatin remodeling techniques to advance understanding of cellular reprogramming mechanisms applicable to pediatric liver disease treatment.