Our projects investigate how cardiac metabolism is altered in heart failure and how nutritional or pharmacologic means can be used to improve cardiac function. While much of what we study involves genetic deletion of the mitochondrial pyruvate carrier 2 (MPC2), we can also extrapolate these findings to traditional models of heart failure.

Nonalcoholic steatohepatitis (NASH) is the severe form of fatty liver disease which involves hepatic injury and fibrosis. If left to progress, NASH can lead to cirrhosis, hepatocellular carcinoma (cancer), and ultimately require liver transplantation. We have several projects to investigate how mitochondrial or certain phospholipid metabolic pathways are involved in the progression of NASH.

We have worked with Cirius Therapeutics and Metabolic Solutions Development Company to define the molecular target and confirm efficacy of new insulin sensitizers for the treatment of both diabetes and nonalcoholic steatohepatitis (NASH). With the support of our preclinical work, one of these compounds, MSDC-0602K, has progressed to clinical trials for the treatment of NASH. Results from a Phase 2b trial have been released, and show many beneficial effects. These results were also published in the Journal of Hepatology. We maintain these productive relationships to continue to study the molecular mechanisms of these new compounds.