Anthony Rosenzweig, MD
- Beth Israel Deaconess Medical Center
- Harvard Medical School
Our research effort focuses on the intracellular signaling pathways that control cell survival and inflammation, and how these contribute to cardiovascular disease. To address these issues, we have used a combination of germline and somatic genetic manipulations in the context of pathophysiologically relevant in vitro and in vivo models of diseases including vascular inflammation/atherosclerosis, ischemic heart disease, and heart failure. Highlights of ongoing projects in each of the two major areas of investigation are discussed below.
Vascular diseases and inflammation:
In many vascular conditions including atherosclerosis, transplant arteriosclerosis, and reperfusion injury, leukocytes play a pivotal role in disease progression. For this reason, we are interested in understanding the molecular basis of leukocyte-endothelial cell interactions. Our focus is on the role of specific intercellular signals (such as chemokines) and the intracellular cascades they initiate. Studies on the intracellular mechanisms involved in endothelial activation have recently focused on modulation of NF-B activation through somatic gene transfer and conditional knockout strategies to understand the role of this pathway the cardiovascular system. More recent studies are exploring the role of endothelial progenitor cells in the context of atherosclerosis.
Congestive heart failure:
We have also used somatic gene transfer and germline manipulations to directly test the contribution of specific intracellular pathways to cardiac dysfunction both in isolated cardiomyocytes and whole hearts in vivo. Initial studies focused on calcium handling proteins, while more recent work has characterized intracellular signaling pathways that modulate cardiomyocyte apoptosis and the relationship of these signaling pathways to those controlling cardiomyocyte function. We have been able to demonstrate a critical role for specific kinases such as PI3-kinase and Akt (Protein Kinase B) in preserving the survival and function of cardiomyocytes both in vitro and in vivo, as well as the importance of Akt-independent pathways in the context. Translational implications of these findings are also being explored in efforts to optimize cardioprotection through expression of secreted ligands that mediate both autocrine and paracrine benefits. Similar strategies may have relevance to optimize survival and function of progenitor cell populations being considered for potential regenerative therapies in the heart.
Dr. Rosenzweig graduated from Harvard College with a degree in biochemistry and molecular biology in 1979 and from Harvard Medical School in 1984. After clinical training in internal medicine and cardiology, Dr. Rosenzweig undertook postdoctoral trainingin the laboratory of Drs. J.G. and Christine Seidman, Department of Genetics at Harvard Medical School from 1988 to 1991. His major focus in the Seidman laboratory was the molecular basis of cardiac hypertrophy through studies of inherited hypertrophic cardiomyopathy and the transcriptional control of hypertrophy-responsive genes. Between 1991 and 1994, Dr. Rosenzweig trained in cell biology and experimental pathology with Dr. Michael A. Gimbrone, Jr, in the Vascular Research Division of the Brigham and Womens Hospital. From 1994 to 2005, Dr. Rosenzweig was an independent investigator in the MGH Cardiovascular Research Center (CVRC) where he served as the Director of the Program in Cardiovascular Gene Therapy from 1999-2005. In 2005, Dr. Rosenzweig became the Director of Cardiovascular Research and Associate Chief of Cardiology at the Beth Israel Deaconess Medical Center. He also serves as an Associate Editor at the New England Journal of Medicine.