Mechanisms of Atherogenesis in Clonal Hematopoiesis

Project Narrative Clonal hematopoiesis, a highly prevalent condition in the elderly, arises from somatic mutations that endow a proliferative advantage to hematopoietic cells and imparts a substantial risk of coronary heart disease. Of the diverse mutations that promote clonal hematopoiesis, JAK2V617F and PPM1D mutations have been associated with DNA damage. The studies proposed here will elucidate the consequences of macrophage DNA damage and Ppm1d mutations on atherosclerosis.