Project Grant R01DK145529

The National Institute of Diabetes and Digestive and Kidney Diseases awarded Mayo Clinic $670,268 on August 15, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to investigate cholangiocyte-driven proinflammatory signaling in primary sclerosing cholangitis (PSC).

The research employs spatial analysis of human PSC liver tissues and murine disease models to define how cholangiocytes engage the innate immune system via neutrophil recruitment and lead to fibroinflammation. Preliminary findings identify mitochondrial dysfunction, cyclic GMP-AMP synthase-STING signaling, neutrophil degranulation, and neutrophil extracellular trap formation as upregulated disease pathways. The project uses patient-derived organoids, cholangiocyte-selective STING-deficient mice, microfluidics, single-cell RNA sequencing, and MRI imaging to investigate cholangiocyte-neutrophil crosstalk, neutrophil recruitment mechanisms, and potential treatment strategies targeting STING signaling.

Mayo Clinic, a tax-exempt nonprofit academic medical center, is the recipient. Place of performance is Rochester, Minnesota. The award period runs through June 30, 2030. The assistance type is Project Grant, a mechanism supporting individual research proposals with competitive peer review.