Dr. Sumanth Prabhu is a Professor of Medicine and Cell, Developmental, and Integrative Biology, and Director of the Division of Cardiovascular Disease at the University of Alabama at Birmingham. Dr. Prabhu is also the Mary G. Waters Chair of Cardiovascular Medicine, and the Director of the Comprehensive Cardiovascular Center. Dr. Prabhu received his medical degree at Jefferson Medical College in Philadelphia, and completed his Internal Medicine Residency and a Research Fellowship at the University of Pittsburgh, followed by a Cardiovascular Disease Fellowship at the University of Texas Health Science Center in San Antonio. He rose quickly through the ranks of Assistant and Associate Professor while in San Antonio, after which Dr. Prabhu moved to the University of Louisville, where he was ultimately appointed the rank of Professor and Director of Heart Failure Research in the Division of Cardiology. Full Manuscript
Dr. Prabhu joined UAB in 2011, as the Director of the Division of Cardiovascular Disease and the Comprehensive Cardiovascular Center, and a member of the UAB Stem Cell Institute. In addition to extensive clinical and administrative duties, Dr. Prabhu directs a highly successful research program, as exemplified by repeated success in obtaining extramural grant support, and publication of seminal research articles in top tier journals, such as PNAS, Circulation, and Circulation Research. Translational research in Dr. Prabhu’s laboratory focuses in part on defining the mechanisms of heart failure, especially the contribution of inflammation to pathological cardiac remodeling, and unlocking the full potential for cardiac repair and regeneration. One of Dr. Prabhu’s most recent research discoveries is detailed in a paper published in Circulation Research in January of this year. Through an elegant series of studies, Dr. Prabhu’s investigative team revealed that activation of splenocytes during heart failure plays a critical role in the pathogenesis of cardiac dysfunction and remodeling. Remarkably, the study shows that these splenocytes retain memory of the heart failure environment, such that transfer of splenocytes from a heart failure mouse into a normal mouse induces hallmarks of cardiac injury in the recipient. These are ground-breaking findings will undoubtedly redefine our understanding of the mechanisms involved in the pathogenesis of heart failure, a disease that plagues more than 5 million Americans.
Rationale: The role of mononuclear phagocytes in chronic heart failure (HF) is unknown.
Objective: Our aim was to delineate monocyte, macrophage, and dendritic cell trafficking in HF and define the contribution of the spleen to cardiac remodeling.
Methods and Results: We evaluated C57Bl/6 mice with chronic HF 8 weeks after coronary ligation. As compared with sham-operated controls, HF mice exhibited: (1) increased proinflammatory CD11b+F4/80+CD206− macrophages and CD11b+F4/80+Gr-1hi monocytes in the heart and peripheral blood, respectively, and reduced CD11b+F4/80+Gr-1hi monocytes in the spleen; (2) significantly increased CD11c+B220− classical dendritic cells and CD11c+/lowB220+ plasmacytoid dendritic cells in both the heart and spleen, and increased classic dendritic cells and plasmacytoid dendritic cells in peripheral blood and bone marrow, respectively; (3) increased CD4+ helper and CD8+ cytotoxic T-cells in the spleen; and (4) profound splenic remodeling with abundant white pulp follicles, markedly increased size of the marginal zone and germinal centers, and increased expression of alarmins. Splenectomy in mice with established HF reversed pathological cardiac remodeling and inflammation. Splenocytes adoptively transferred from mice with HF, but not from sham-operated mice, homed to the heart and induced long-term left ventricular dilatation, dysfunction, and fibrosis in naive recipients. Recipient mice also exhibited monocyte activation and splenic remodeling similar to HF mice.
Conclusions: Activation of mononuclear phagocytes is central to the progression of cardiac remodeling in HF, and heightened antigen processing in the spleen plays a critical role in this process. Splenocytes (presumably splenic monocytes and dendritic cells) promote immune-mediated injurious responses in the failing heart and retain this memory on adoptive transfer.
My academic interests focus on heart failure (HF) in both the clinic, where I attend to patients with advanced HF, and in the basic research laboratory, where I have been studying the cellular and molecular mechanisms of cardiac remodeling, dysfunction, and repair in HF. My laboratory routinely incorporates physiological assessments of murine cardiac function (e.g., echocardiography and pressure-volume analysis) with cellular and molecular studies. I have a particular interest in the role of inflammation in HF, and the translation of new therapeutic approaches to alleviate inflammation. Recently, we uncovered a novel pro-inflammatory and cardio-injurious role for mononuclear splenocytes in HF (i.e., the cardiosplenic axis), a discovery that has provided new perspectives as to the basis and mechanisms of inflammation-mediated injury in the failing heart. Elucidating the role of immune cells in the pathogenesis of inflammation and cardiac repair/remodeling is currently a primary focus of the laboratory.