Partha Dutta, DVM, PhD
Associate Professor of Medicine, Division of Cardiology
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.
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.
Education and Training
MS, Wichita State University, KS, 2006
PhD, University of Wisconsin-Madison, WI, 2010
Instructor, Harvard Medical School, 2015
For a complete bibliography, click here.
View Selected Papers
- Florentin J, Zhao J, Tai YY, Vasamsetti SB, O’Neil SP, Kumar R, Arunkumar A, Watson A, Sembrat J, Bullock GC, Sanders L, Kassa B, Rojas M, Graham BB, Chan SY*, Dutta P*. Interleukin-6 mediates neutrophil mobilization from bone marrow in pulmonary hypertension. Cell Mol Immunol. 2021 Jan 8. doi: 10.1038/s41423-020-00608-1. Epub ahead of print. PMID: 33420357. *Co-senior authors
- Vasamsetti SB, Coppin E, Zhang X, Florentin J, Koul S, Gotberg M, Clugston AS, Thoma F, Sembrat J, Bullock GC, Kostka D, St. Croix CM, Chattopadhyay A, Rojas M, Mulukutla S, Dutta P. Apoptosis of hematopoietic progenitor-derived adipose tissue resident macrophages contributes to insulin resistance after myocardial infarction. Sci Trans Med, 2020
- Zhao J, Florentin J, Tai Y, Torrino S, Ohayon L, Brzoska T, Tang T, Negi V, Woodcock CC, Risbano M, Nouraje SM, Sundd P, Bertero T*, Dutta P*, Chan SY*. Long range endocrine delivery of circulating miR-210 to endothelium promotes pulmonary hypertension. Circ Res. 2020. *Co-senior authors.
- Hoyer FF+, Zhang X+, Coppin E, Vasamsetti SB, Modugu G, Schloss M, McAlpine CS, Iwamoto Y, Libby P, Naxerova K, Swirski FK, Dutta P*, Nahrendorf M*. Bone marrow endothelial cells regulate myelopoiesis in diabetes. Circulation. 2020. Accepted for publication. +Co-first authors. *Co-senior authors and Co-corresponding authors.
- Vasamsetti SB, Florentin J, Coppin E, Stiekema L, Zheng KH, Nisar MU, Levinthal D, Rojas M, Stroes ES, Kim K, Dutta P. Sympathetic neuronal activation triggers myeloid progenitor proliferation and differentiation. Immunity. 2018. pii: S1074-7613(18)30240-1. doi: 10.1016/j.immuni.2018.05.004. PMID: 29958804.