Next Generation of Direct Cardiac Reprogramming
Description: Heart disease remains the leading cause of morbidity and mortality in the elderly, who are particularly vulnerable to invasive procedures and long-term therapies. Direct reprogramming of cardiac fibroblasts (CFs) into induced cardiomyocytes (iCMs) offers a promising alternative strategy. Through support from my initial AHA Established Investigator Award (EIA), my lab has optimized reprogramming conditions, uncovered molecular mechanisms, and advanced understanding of fibroblast plasticity during aging, leading to over 40 publications and the successful career development of multiple trainees. Building on our recent findings that efficient iCM reprogramming requires enhanced mitochondrial biogenesis, fusion, and respiratory capacity, we now propose to define how mitochondrial dynamics change with age and whether restoring a youthful mitochondrial state can improve iCM generation in aged fibroblasts. Using integrated metabolic assays, high-resolution imaging, and our newly developed MitoSinCe2 pipeline, coupled with AI-driven analysis, we will establish mitochondria as an independent dimension of iCM reprogramming during aging. These studies will improve the efficiency and quality of cardiac reprogramming in old hearts and provide the foundation for future extramural funding to advance therapies for elderly patients with heart failure.
Funder: American Heart Association
Amount: $80,000
Funding type: research
Funder scheme: Bridge Established Investigator Award
Start date: 2026-01-01
End date: 2026-12-31
Investigators: Li Qian, Li Qian
Institution: The University of North Carolina at Chapel Hill
Subfield: Molecular Biology
Domain: Life Sciences
Funded outputs count: 1
Funder award ID: 26BEIA1560994
OpenAlex ID: G8046677104