Our laboratory investigates the interplay between the hematopoietic and the cardiovascular systems in the context of cardiovascular disease, with a particular focus on the pathophysiology of atherosclerosis, the underlying cause of most heart attacks and strokes. In our research, we always aim to combine human studies, animal models and cell culture experiments, and to follow a “human to mouse and back” approach: use data obtained in human studies to generate hypothesis that will be tested in mouse models, with the ultimate aim of using the knowledge obtained in mice to design diagnostic tools, therapies or preventive care strategies that can be applied to humans.
One of the main lines of research of the laboratory is aimed at understanding how acquired mutations in blood cells, which are known to be linked to hematological cancers, may also contribute to the development of atherosclerosis. Exome sequencing studies in humans have shown that aging is associated with the acquisition of somatic mutations in the hematopoietic system, which in some cases provide a competitive growth advantage to the mutant cell and thus allow its clonal expansion (i.e. somatic mutation-driven clonal hematopoiesis, also designed as clonal hematopoiesis of indeterminate potential or CHIP). Unexpectedly, the presence of these age-related mutations has been associated with a higher incidence of atherosclerotic CVD. These epidemiological findings provide rationale for the provocative hypothesis that somatic mutations in blood cells contribute to atherosclerosis and related cardiometabolic conditions. Testing this hypothesis and its clinical implications is one of our main objectives. Our research on this topic may lead to the identification of new pathogenic mechanisms underlying atherosclerotic CVD, and could provide the basis for the design of personalized therapies or preventive care strategies for individuals carrying somatic mutations in specific genes.
Beyond our research on somatic mutations and clonal hematopoiesis, other projects in the laboratory are broadly focused on elucidating new mechanisms underlying the connection between aging and vascular inflammation.