Project Grant R01HL182870

The National Heart, Lung, and Blood Institute awarded Icahn School of Medicine at Mount Sinai $839,536 on August 1, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to investigate how lifestyle factors selectively modify clonal hematopoiesis in atherosclerosis through immuno-metabolic reprogramming.

The research will examine whether sleep and exercise—evolutionarily conserved behaviors that promote cardiovascular and immune health—can modify the evolution of clonal hematopoietic stem cell mutations and their associated atherosclerosis development. Preliminary data in humans and mice demonstrate that clonal hematopoiesis mutant cells respond selectively to lifestyle interventions, with sleep and exercise reprogram­ming the immuno-metabolic status of mutant cells in the bone marrow and aorta while leaving neighboring wild-type cells unaffected.

Aim 1 will model three mutations and clonal hematopoiesis-accelerated atherosclerosis in high-fat diet-fed LDLR-knockout mice exposed to 12 weeks of sleep fragmentation, voluntary exercise, or sedentary lifestyle. The study will track mutant cell expansion, measure hematopoietic stem cell abundance, proliferation, inflammasome status, and metabolic profile in bone marrow and spleen, and conduct genetic deletion and pharmacological blockade experiments to causally test whether lifestyle influences key inflammatory and metabolic pathways. Aim 2 will assess how sleep and exercise alter clonal hematopoiesis disease progression.

Performance occurs in New York, New York, with period of performance extending from August 1, 2026, through May 31, 2030. The award is a Project Grant, the standard NIH research assistance type.