Investigating the role of the aged bone marrow microenvironment in accelerating age-related hematologic malignancies such as clonal hematopoiesis
The world population is aging, and lifespan is increasing but unfortunately health span is not increasing simultaneously. As we age, we acquire somatic mutations in our hematopoietic stem cells (HSCs), some of which can confer a competitive advantage causing clonal HSC expansion. This clonal expansion is known as clonal hematopoiesis (CH) and is present in 10-15% of individuals aged 70 years or older. Individuals with CH have an increased risk of progression to hematologic malignancy compared to age-matched controls, as well as a higher risk of coronary heart disease and ischemic stroke. The long-term goal of my work is to improve understanding of these mechanisms and discover interventions to stop or slow clonal HSC expansion and therefore decrease risk of CH-associated diseases in aging individuals. Successful completion of this project will determine the mechanisms by which, and extent to which, the aged BM microenvironment accelerates development of CH. Targeting these mechanisms has high potential to prevent or reduce clonal hematopoietic burden, and thus reduce incidence of hematologic malignancy, coronary heart disease, and ischemic stroke in aging populations.