The heart functions as a pump that cycles between contraction and relaxation in order to provide nutrients and oxygen and remove waste from all organs. Our laboratory studies how metabolism affects heart and mitochondrial diseases. We are particularly interested in the emerging roles of NAD+ metabolism in these diseases. Recent studies highlight the importance of NAD+-dependent pathways in mitochondrial and cellular functions, disease pathogeneses and therapeutics. Our goal is to discover how NAD+ metabolism is involved in disease pathogenesis to improve therapeutic strategies.

Diabetes, hypertension and aging are important risk factors for the progression of heart failure. We recently described the roles of NAD+ redox imbalance in promoting heart failure progression induced by chronic pressure overload (a hypertension model). Our laboratory now focuses on determining the roles of NAD+ metabolism in cardiac dysfunction induced by metabolic disorders such as diabetes. Using multi-omics analyses and genetic models targeting NAD+ metabolism, we will dissect how NAD+ metabolism plays important roles in cardiac dysfunction induced by diabetes, and by other risk factors of heart failure.

Our laboratory also works on understanding how NAD+ metabolism contributes to the pathogenesis of mitochondrial disease, e.g., Leigh syndrome. Patients with Leigh syndrome harbor mutations in mitochondrial genes and manifest neurometabolic disorders, cardiomyopathy and early death. We recently showed that elevations of NAD+ levels improve lifespan and healthspan in a mouse model of Leigh syndrome. Using the tools and models targeted for NAD+ metabolism, we hope to identify disease mechanisms and to further improve therapeutic strategies in treating mitochondrial disease.