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NOBEL PRIZE 2026

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NIHNATIONAL HEART, LUNG, AND BLOOD INSTITUTE

FKBP5 AND CARDIAC ARRHYTHMOGENESIS

Active
Institution
Baylor College of Medicine, TX
Principal investigator
Na Li
Funding
$99K
Duration
2023–2027
Open portfolio

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Abstract

PROJECT SUMMARY Atrial fibrillation (AF) is the most frequent arrhythmia. Reduced mRNA expression of FK506-binding protein 5 (FKBP5) was recently discovered in a transcriptomic study with AF patient tissues. However, the functions of FKBP5 in heart are unknown. Preliminary studies revealed that cardiac specific loss of FKBP5 promotes the AF development. The long-term goal of this project is to elucidate the function of FKBP5 in the heart and the underlying arrhythmogenic mechanisms associated with the FKBP5 deficiency, with a view toward developing new therapeutic strategies to reduce AF risk. We will test the overarching hypothesis that the FKBP5 deficiency can enhance atrial arrhythmogenesis via a ‘double-hit’ mechanism, i.e. enhancement of Na+/Ca2+ exchanger 1 - mediated triggered activity in cardiomyocytes, and promotion of fibrotic remodeling due to altered fibroblast function. We will elucidate the proarrhythmic mechanisms due to cardiomyocyte-specific or fibroblast-specific loss of FKBP5, respectively. We will also evaluate the anti-AF potential of targeting the FKBP5 pathway. The proposed studies will unveil the critical role of FKBP5 in regulating cardiac electrophysiology and provide new insights to molecular mechanisms of AF.

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NATIONAL HEART, LUNG, AND BLOOD INSTITUTER01Integrative Myocardial Physiology/Pathophysiology B Study Section[MPPB]cardiacdeficiencyatrial fibrillationunknown preliminaryatrialtest overarchingpotential targetingmrna expression

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