Federal Project Grant Award Summary

Vanderbilt University Medical Center received $874,741 in funding from the National Institute of Diabetes and Digestive and Kidney Diseases under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) for a project investigating transcriptional mechanisms of fibrosis in metabolic dysfunction-associated steatohepatitis (MASH). The award, effective June 1, 2026, through February 28, 2030, supports basic biomedical research aimed at identifying and characterizing transcriptional regulators of collagen production in hepatic stellate cells. The research deliverables include genome-scale enhancer mapping analyses of human MASLD (metabolic dysfunction-associated steatotic liver disease) liver tissues, CRISPR screening studies to validate transcription factors regulating collagen synthesis, and chromatin profiling to establish direct molecular mechanisms by which identified factors control collagen gene expression in both human and mouse models.

This research addresses a critical gap in understanding liver fibrosis progression, a key inflection point in MASH disease severity that can advance to cirrhosis, liver failure, and hepatocellular carcinoma. The project specifically identified ZNF469 (zinc finger protein 469) as a modulator of collagen production and established its role in regulating collagen gene expression through loss-of-function studies and chromatin analysis. The findings provide a foundation for potential therapeutic development targeting transcriptional regulators of hepatic fibrosis, with direct relevance to the NIDDK programmatic objective of improving understanding, prevention, diagnosis, and treatment of liver disease and metabolic disorders.