Systems Biology of Cardiovascular Disease

My lab pursues two central research themes:

i) Development of next generation imaging tools to probe biology in vivo and to improve clinical decision making

ii) The pathobiology of atherosclerosis and its complications

I currently focus on the complex interactions of the immune, central nervous and hematopoietic system in cardiovascular disease.

Inflammation in Atherosclerosis.

Approximately 20% of patients who have had a heart attack will have a second within a year. Why?

In a study published in Nature, we describe the underlying mechanism that leads to secondary heart attacks in patients. We are now investigating therapeutic implications of this discovery.

Immunity in Heart Failure

Advanced heart failure has 50% mortality, and there are 6 million heart failure patients in the USA, creating a pressing medical need. Focusing on basic wound healing processes that occur within the first two weeks after ischemic injury, my research lead to the insight that early infarct healing is a key period after acute MI during which therapeutic interventions (there are none today) could change the long-term course of disease.

The healing infarct is a special wound: exposed to the high strain of blood pressure and cardiac motion, it cannot 'rest' like a broken bone in a cast. If healing derails, the infarct scar expands, the heart dilates, and a vicious cycle of remodeling results in heart failure.

My lab studies macrophages and their circulating progenitors (monocytes) in the setting of infarction. We discovered that there are 2 monocytic phases after MI. In the first 3 days, the infarct recruits inflammatory monocytes, then, the heart switches to a resolution phenotype on day 4.

If a phase is missing, wound healing is deficient (JEM 2007, >500 citations). These findings have been reproduced in humans. We further discovered a new function of the spleen (Science 2009) and hematopoiesis activation in the setting of myocardial infarction (JEM 2012).

The spleen harbors a large ready-to-deploy monocyte reservoir that is released post-MI through increased angiotensin-2 levels. Infarction triggers a transfer of stem cells from the bone marrow to the spleen, outsourcing production of inflammatory leukocytes.

About the MGH Research Scholars

The MGH Research Scholars Program was established to support early career researchers with innovative yet unproven ideas that have the potential to transform the future of medicine. Funded 100% through philanthropy, this program gives researchers the freedom and flexibility they need to follow the science wherever it leads. Time and time again, history has shown that brilliant scientists who are given free rein to explore new frontiers are the ones who make the greatest, often wholly unexpected, advances.

Learn more about the MGH Research Scholars Program.

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