Federal Grant Award Summary

Yale University received a $802,715 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), effective March 1, 2026 through January 31, 2030. The research initiative investigates the role of pathogen-induced biliary inflammation in the pathogenesis of sclerosing cholangiopathies, particularly primary sclerosing cholangitis (PSC), a chronic disease characterized by progressive fibrosis and dilation of bile ducts that currently lacks effective treatment options beyond liver transplantation. The project will examine how biliary epithelial cells respond to gut-derived pathobionts, pathogen-associated molecular patterns, and pro-inflammatory mediators, with particular focus on enterococcus species colonization and its association with disease progression in PSC patients.

The research deliverables include investigations of human cholangiocyte responses to pathogenic microorganisms using patient-relevant cellular models developed through recent advances in organoid technology, analysis of interactions between biliary cells and immune cells, and comparative studies to identify abnormal inflammatory mechanisms specific to PSC. By elucidating the mechanisms underlying pathogen-induced biliary inflammation, this research aims to generate foundational knowledge that may inform future preventive and therapeutic interventions for sclerosing cholangiopathies and related liver diseases.