Accelerating Breakthrough Discoveries into Medicines

Gerald I. Shulman, MD, PhD

Dr. Shulman is developing a therapy to address non-alcoholic fatty liver disease, a complication of type 2 diabetes.

Gerald Shulman, MD, PhD is an Investigator of the Howard Hughes Medical Institute and the George R. Cowgill Professor of Physiological Chemistry, Medicine and Cellular & Molecular Physiology at Yale University. He is also Co-Director of the Yale Diabetes Research Center.

Non-alcoholic fatty liver disease (NAFLD) affects 1 in 3 Americans and plays a major role in the pathogenesis of type 2 diabetes. NAFLD is also a key predisposing factor for the development of non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. There are currently no available medications that effectively reverse NAFLD/NASH. Dr. Shulman and his team are addressing this unmet need by examining the effects of a novel controlled release mitochondrial protonophore (CRMP) on the reversal of NAFLD/NASH and diabetes in a transgenic mouse model of NASH and type 2 diabetes.

Over the next two years, the Shulman lab will be to examining the safety and efficacy for CRMP to reverse NAFLD/NASH and type 2 diabetes in a transgenic (A-ZIP) mouse model of severe lipodystrophy. They hypothesize that by promoting a subtle sustained increase in hepatic mitochondrial inefficiency CRMP will reverse NAFLD/NASH, liver fibrosis and insulin resistance in rodent models of NAFLD/NASH and type 2 diabetes in a safe and effective manner.

Dr. Shulman’s work with Harrington Discovery Institute builds on very strong preliminary data demonstrating that this approach can safely reverse hypertriglyceridemia, fatty liver, steatohepatitis and liver fibrosis in rat models of NAFLD/NASH and type 2 diabetes (Perry et al. Science 2015). Taken together, these preliminary results demonstrate that the beneficial effects of CRMP on NASH, insulin resistance and type 2 diabetes can be dissociated from systemic toxicities of mitochondrial uncouplers and are proof of concept for developing liver-targeted mitochondrial protonophores for the treatment of NASH and type 2 diabetes.

Dr. Shulman completed his undergraduate studies in biophysics at the University of Michigan, and he received his M.D. and Ph.D. degrees from Wayne State University. Dr. Shulman is a Fellow of the American Association for the Advancement of Science, Fellow of the American Physiological Society, Master of the American College of Endocrinology and he has been elected to the American Society for Clinical Investigation, the Association of American Physicians, the National Academy of Medicine and the National Academy of Sciences.

Dates to Know

April 5, 2017
Letter of Intent Deadline

LOI Guidelines
Download the Application Guidelines (PDF)

May 31, 2017
Full Application Deadline (For those invited)

December 2017
Awardees Notified

Harrington Project

The Harrington Discovery Institute is the nonprofit arm of the Harrington Project for Discovery & Development, an international initiative supporting breakthrough research by physician-scientists. The Project is a new and powerful approach to address some of the challenges hindering advancement of medicine today.

The Harrington Grant is an important part of the overall pharmaceutical research initiative created by The Harrington Project.

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