Hematovascular Pathophysiology
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 atherosclerotic cardiovascular disease and other age-related conditions. 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 within the hematopoietic system and its progeny, which includes immune cells that are at the center of many age-related chronic conditions. This phenomenon is called somatic mutation-driven clonal hematopoiesis or clonal hematopoiesis of indeterminate potential (CHIP) and has been associated with a higher incidence of atherosclerotic cardiovascular disease and other chronic inflammatory disorders, but the mechanisms underlying this association remain largely undefined. Investigating these mechanisms and the pathophysiological and clinical relevance of clonal hematopoiesis is one of our main objectives. This research may lead to the identification of new pathogenic mechanisms underlying cardiovascular disease, 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 acquired mutations and clonal hematopoiesis, other projects in the laboratory are broadly focused on elucidating new mechanisms underlying the connection between aging and vascular inflammation, with a particular interest in sex differences in inflammation during atherosclerosis development.