Federal Project Grant Award Summary

The Board of Regents of the University of Nebraska received a $529,273 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). The award, effective April 1, 2026 through March 31, 2030, supports research into the MATRIN3-CAR-Thrombin Axis in hepatic inflammation and fibrosis. The research investigates the molecular mechanisms linking steatosis, inflammation, and coagulation in metabolic dysfunction-associated steatohepatitis (MASH), a progressive liver disease affecting approximately 30% of U.S. adults. The project utilizes genetic and transcriptomic analyses, single-nucleus multiome sequencing, and intercellular communication studies to identify therapeutic targets for treating MASH.

The research focuses on characterizing how MATRIN3, a DNA- and RNA-binding protein, regulates hepatic steatosis through the constitutive androstane receptor (CAR) transcription factor and downstream thrombin signaling pathways. Deliverables include mechanistic insights into hepatocyte and hepatic stellate cell interactions, identification of new CAR target genes including the prothrombin-encoding F2 gene, and clarification of protease-activated receptor signaling patterns in liver fibrosis. These findings are intended to advance the understanding of MASH pathogenesis and inform development of novel therapeutic approaches to prevent disease progression.