Fuster, Jose Javier

Primary Appointment

Medicine: Cardiovascular Medicine


  • PhD, , University of Valencia

Contact Information

Email: jjf4s@eservices.virginia.edu

Research Interests

Evaluation of new mechanisms that link aging to cardiovascular disease

Research Description

Research in the Fuster Lab is focused on the evaluation of new mechanisms that link aging to cardiovascular disease (CVD), with an especial interest in the pathophysiology of atherosclerosis. Within this setting, our main line of research is aimed at investigating the potential causal role of somatic mutations in blood cells in age-related cardiovascular disease. The accumulation of somatic DNA mutations over time is a hallmark of aging in many tissues, particularly in highly proliferative tissues such as the hematopoietic system. It has been estimated that by age 50 an individual would accumulate an average of five coding gene mutations within each hematopoietic stem cell (Welch et al, Cell, 2012), which sets the stage for a robust Darwinian selection of mutations that provide a competitive advantage to the mutant cell. Exome sequencing studies in humans suggest that between 10 and 20% of healthy individuals greater than 60 years old exhibit somatic mutations that provide such a competitive advantage, leading to the clonal expansion of the mutant cell within the hematopoietic stem cell population and its blood cell progeny. Unexpectedly, this somatic mutation-driven clonal hematopoiesis has been associated with an increased risk of atherosclerotic CVD (Jaiswal et al. N Engl J Med 2014, 2017), suggesting the provocative hypothesis that somatic mutations in blood cells contribute to atherosclerosis. Testing this hypothesis using a combination of human studies, animal models and cell culture experiments is the main objective of the Fuster Lab. In this regard, we have recently provided the first mouse genetic evidence supporting the notion that the clonal expansion of Tet2-mutant hematopoietic cells is causally connected to atherosclerosis development (Fuster et al, Science 2017).

Selected Publications