Federal Grant Award Summary

The University of Pennsylvania received a $789,828 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 June 1, 2026, with completion targeted for February 28, 2030. The project delivers theoretical and experimental research addressing the tissue mechanics underlying fibrosis progression in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), a rapidly growing global health epidemic affecting over one-third of the population. The research focuses on developing validated computational models and conducting experimental studies using primary human hepatocytes and animal models to elucidate how cholesterol crystal formation drives disease progression through alterations in liver tissue stiffness, hepatocyte cytoskeletal organization, and nuclear structure—factors that current clinical methods cannot reliably predict.

The grant deliverables include predictive models and experimental validation of cholesterol crystal impacts on liver tissue mechanics, including effects on collagen network plasticity and tissue stiffness based on crystal size and shape; examination of how cholesterol crystals alter hepatocyte cytoskeletal organization and cytoskeleton-nucleus interactions; and determination of chromatin structure changes induced by these crystalline inclusions. These research products are designed to advance scientific understanding of MASLD pathogenesis and ultimately support development of improved clinical tools for identifying patients at risk of progression to severe liver disease and hepatocellular carcinoma.