Project Grant R01HL189184

The National Heart, Lung, and Blood Institute awarded Yale University $838,491 on September 1, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to identify novel gene variants that drive endothelial cell activation during atherosclerotic cardiovascular disease.

The recipient will elucidate mechanisms by which gain-of-function defects in ZFYVE21, an endosome-associated protein highly expressed in endothelial cells, contribute to endothelial cell activation and exacerbate atherosclerotic lesions and ischemic complications. The project will employ in silico, in vitro, and in vivo approaches, including mechanistic studies in humanized mouse models and analysis of patient samples, to test the clinical relevance of identified pathways. This work builds on the discovery that individuals from four unrelated families with severe atherosclerotic cardiovascular disease—including myocardial infarction and sudden cardiac death—harbor ZFYVE21 gain-of-function defects; the source indicates ZFYVE21 gene defects have not been mechanistically addressed in any human disease prior to this award.

Performance occurs in New Haven, Connecticut. The period of performance runs from September 1, 2026, through June 30, 2030. The award is classified as a Project Grant.