Project Grant R01DK148866

The National Institute of Diabetes and Digestive and Kidney Diseases awarded Weill Medical College of Cornell University $585,556 on August 10, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to investigate endothelial metabolic control of liver homeostasis and response to damage.

The research examines how liver sinusoidal endothelial cells (LSECs) lose their specialized phenotype during liver fibrosis through a process called capillarization, in which metabolic changes drive the transition to a generic capillary endothelial phenotype. The project hypothesizes that alterations in LSEC metabolic regulation underlie this capillarization process, leading to increased inflammatory response and loss of the factors—including HGF, WNT2, WNT9B, and RSPO3—that LSECs normally secrete to maintain hepatocyte function and zonation. Preliminary findings indicate that LSEC adaptation involves changes in cell shape and mitochondrial adaptation, pointing to a central role of the mTOR pathway. Understanding the molecular mechanisms driving LSEC dysfunction during liver fibrosis may reveal novel treatment approaches for liver disease.

The award is structured as a Project Grant. Performance runs through April 30, 2031, at Weill Medical College's location in New York, New York.