Federal Project Grant Award Summary

The National Heart, Lung, and Blood Institute (NHLBI) awarded the University of Pennsylvania a $765,129 Project Grant effective May 1, 2026, through January 31, 2030, under the Cardiovascular Diseases Research program (CFDA 93.837). This research initiative will investigate the mechanisms by which sodium-glucose cotransporter 2 inhibitors (SGLT2i) protect against heart failure by examining their role in activating pantothenate kinase (PANK) and enhancing coenzyme A (CoA) metabolism in cardiac tissue. The project will deliver comprehensive scientific findings addressing four primary research objectives: characterizing the consequences of SGLT2i on cardiac CoA metabolism and fuel utilization; testing the role of cardiac PANK in heart failure protection in vivo; identifying the molecular mechanism of PANK activation by SGLT2i; and initiating a discovery campaign for novel small molecules that target PANK independently of SGLT2.

The research outputs will include detailed structural and physiological understanding of how SGLT2i compounds interact with PANK, preclinical data supporting mechanism of action, and preliminary findings from a small-molecule discovery program designed to develop therapeutics that improve efficacy while reducing adverse effects associated with existing SGLT2i treatments. These deliverables will advance the scientific understanding of cardiac metabolism in heart failure—the leading cause of hospitalization in Americans over age 65—and potentially enable the development of more effective therapeutic interventions targeting metabolic pathways in cardiovascular disease.