My laboratory broadly examines the molecular events that drive cardiovascular cell growth, differentiation and cell death. A major focus has been to elucidate mechanisms of inter-tissue communication and understand how these systems contribute to physiological versus pathological tissue growth in the cardiovascular system, particularly as they relate to systemic metabolic dysfunction and cardiovascular disease (CVD).
Our recent studies investigate how “clonal hematopoiesis” functions as a causal risk factor for cardio-metabolic diseases. Recent large exome sequencing studies in humans have shown that aging is frequently associated with the appearance of pre-leukemic, somatic mutations in the hematopoietic system that provide a competitive growth advantage to the mutant cell and allow its clonal expansion. These aberrant clonal events in the hematopoietic system have been found to be associated with greater risk of CVD. Using murine genetic models, our work suggests that there is a causal connection between clonal hematopoiesis and CVD, and we have elaborated aspects of the underlying mechanisms. The Walsh lab also collaborates with clinician-scientists to assess the status of clonal hematopoiesis in patient cohorts.