Profiles

My group is interested in understanding the impact of genetic variants on the function of immune cells and on predisposition to pathologies driven by the immune system. In particular, we are interested in studying defects of the DNA methylation pathway in the context of aging-associated clonal hematopoiesis. Acquired mutations in DNMT3A (a writer of DNA methylation) and TET2 (an eraser of DNA methylation) are common in the hematopoietic stem cells of elderly individuals, estimated to affect more than 10% of adults over the age of 65. These mutations increase the risk for various age-related comorbidities such as atherosclerosis, thereby nearly doubling the mortality rate of affected individuals. We hypothesize that these mutations impair DNA methylation remodeling that occurs during the differentiation of hematopoietic stem cells, leading to altered gene expression and function of terminally differentiated immune effector cells such as macrophages. We use various cutting-edge human genetic and epigenetic tools and experimental model systems such as human pluripotent stem cell-derived macrophages to address our questions.