Associate Professor of Medicine, Division of Cardiology

Bio

His current research interests focus on immunology of cardiovascular and metabolic diseases. He is investigating how myeloid cells, such as monocytes and macrophages, induce inflammation. Innate inflammatory cells, such as monocytes and macrophages, are important in cardiovascular disease. After being recruited to atherosclerotic plaques or myocardial infarcts, myeloid cells secrete proteolytic enzymes, e.g. cathepsin and matrix metalloproteinase that digest the extracellular matrix, render atherosclerotic plaques unstable and dilate the myocardium. This results in heart failure or plaque rupture, which triggers a secondary myocardial infarction. Although newly recruited cardiac macrophages are well known for aggravating inflammation after MI, the mechanisms of why these macrophages are inflammatory are not well known.

Dr. Dutta’s long term goal is to understand the cross talk among cellular metabolism, epigenetics and inflammation. His research team has attenuated atherosclerotic plaque inflammation by modulating myeloid cell functions. However, our knowledge on how cell metabolism increases inflammation via epigenetic editing is limited. Moreover, despite the health burden caused by MI, how myeloid cell metabolism can deteriorate cardiac function and promote heart failure after MI is not known. Dr. Dutta wants to devote his career to improve our knowledge on understanding the causative links between metabolism-mediated epigenetic changes and hyperinflammation. His ultimate goal is to identify therapeutic targets in these processes and develop therapeutic avenues for patients with MI by targeting metabolic pathways in macrophages.

Research Interests

Cardiovascular disease is the leading cause of death in developed countries. Inflammation aggravates outcome of cardiovascular disease including atherosclerosis and infarct healing after myocardial infarction (MI) (Leuschner* and Dutta* et al., Nature Biotechnology, 2011). During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaques in the arterial wall and cause their rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. We showed that the systemic response to ischemic injury aggravates chronic atherosclerosis (Dutta et al., Nature, 2012). After myocardial infarction or stroke, ApoE-/- mice developed larger atherosclerotic lesions with a more advanced morphology and inflammation. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. We have recently shown that MI results in de novo insulin resistance in mice and patients without a history of diabetes (Vasamsetti et al., Science Translational Medicine, 2020). Furthermore, the sympathetic nervous system plays a major role in proliferating inflammatory cell progenitors and exacerbation of inflammation (Vasamsetti and Florentin et al., Immunity, 2018)

One of our current research interests focuses on immunology of cardiovascular disease. We are investigating how myeloid cells, such as monocytes and macrophages, induce inflammation in metabolic disease such as type II diabetes and cardiovascular disease such as myocardial infarction. The ultimate goal of the lab is to develop potential therapeutic avenues to check generation of myeloid cells in the bone marrow and spleen, and recruitment of myeloid cells to sites of inflammation such as adipose tissue and the myocardium. We are also keenly interested to investigate differential functions of tissue resident and monocyte-derived macrophages in steady state and disease.

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Education and Training

Selected/Representative Publications

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