Project Grant R01DK140492

The National Institute of Diabetes and Digestive and Kidney Diseases awarded $803,565 to the University of California, Davis on September 1, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to develop and characterize an orally delivered nanodrug for metabolic disease treatment.

The project targets metabolic dysfunction-associated steatohepatitis (MASH) and type 2 diabetes mellitus by addressing gut dysbiosis and restoring impaired signaling along the gut-liver axis. The research centers on designing and synthesizing ProRA, a nano-formulated drug that co-delivers propionic acid (an HDAC inhibitor) and all-trans retinoic acid linked to polyvinyl alcohol, which self-assembles into nanomicelles. In preclinical models—diet-induced obese mice and bile acid receptor FXR knockout mice—oral ProRA therapy improves insulin sensitivity, treats MASH, and reduces hyperlipidemia and splenomegaly. The work is motivated by evidence that human colorectal cancer and hepatocellular carcinoma exhibit elevated protein deacetylases and reduced short-chain fatty acid signaling, and that HDAC inhibitors enhance intestinal retinoic acid signaling consistently reduced in these cancers.

Performance occurs in Sacramento, California, with a period of performance extending from September 1, 2026, through May 31, 2030. The award is classified as a Project Grant.