Mitochondrial regulation in cardiovascular and cancer biology

National Heart, Lung, And Blood Institute

Investigators

Linked publications & trials

Abstract

We are focusing on the regulation of mitochondrial function that impacts cardiovascular exercise capacity with implications for tumorigenesis. We have shown that p53 balances the energy generated by respiration and glycolysis and promotes aerobic metabolism through it positive regulation of mitochondrial function. An interesting effect of this biological mechanism is that mice deficient in p53 display profound deficiencies in aerobic exercise capacity, revealing a new function for a well-studied tumor suppressor gene mainly associated with cell cycle and genomic regulation. We are further characterizing the biology underlying these observations and translating them to humans through clinical studies. Specifically, we are studying metabolic functions using both clinical and basic studies in individuals with Li-Fraumeni syndrome, a premature cancer syndrome caused by germline mutations in the p53 gene. The goal of this research is to derive basic insights that may help in the development of new strategies for preventing cancer in specific populations such as in Li-Fraumeni syndrome and also for improving general human health.