Project Grant K08HL186462

Federal Grant Award Summary

The University of Michigan received a $169,560 Project Grant from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837), effective July 1, 2026 through June 30, 2031. This award supports mechanistic research into desmoplakin cardiomyopathy (DSP-CM), an arrhythmogenic condition affecting young adults that results in impaired cardiac function, myocardial fibrosis, and sudden cardiac death. The funded research will deliver scientific insights into how mechanical stress, including high-intensity exercise, interacts with desmoplakin haploinsufficiency to drive cardiac tissue injury and arrhythmias, utilizing fiber-aligned engineered heart tissues and a novel DSP mouse model developed by the investigator.

The project's primary deliverables include (1) tissue-level pathology data characterizing the impact of mechanical load and exercise on fibrosis and arrhythmias in desmoplakin-deficient models through exercise protocols, functional assessments, and spatial transcriptomics; and (2) evaluation of adeno-associated virus (AAV)-mediated gene therapy strategies to rescue desmoplakin haploinsufficiency and prevent pathological outcomes. Research will be conducted at the University of Michigan's Ann Arbor campus through integrated mechanistic studies bridging human tissue models and in vivo mouse physiology, with the ultimate goal of informing therapeutic interventions for this rare genetic cardiomyopathy.