Location and Contact Information
Research in the Steinberg laboratory focuses on the mechanisms that underlie the physiologically important changes in cardiomyocyte adrenergic receptor responsiveness that accompany normal cardiac development, that influence the evolution of heart failure, or that contribute to cardiac injury in the setting of ischemia-reperfusion injury and oxidative stress. The studies take advantage of a wide range of reductionist molecular and cell biological approaches in both cell culture and in vitro models to study the expression and subcellular localization of adrenergic receptor subtypes, to identify the adrenergic receptor binding partners and effectors that dictate signaling specificity in cardiomyocytes, and to understand the molecular basis for catecholamine-dependent cardiomyocyte remodeling. One area of particular interest has been the stimulus- (in some cases redox-) dependent post-translational modifications on signaling kinases such as protein kinase C and protein kinase D that alter their enzymology. Recent studies also have focused on O-glycan-regulated proteolytic cleavage of the beta1-adrenergic receptor extracellular N-terminus as a mechanism that calibrates catecholamine activation of downstream pro-apoptotic versus cardioprotective responses. In each case, these studies have identified novel molecular determinants that can serve as druggable targets.
About Dr. Steinberg
Dr. Susan Steinberg is a Professor of Pharmacology at Columbia University. She received a BS in Biology from MIT, an MD from Harvard Medical School, and completed residency training in Internal Medicine and a Fellowship in Endocrinology and Metabolic Diseases at the Vagelos College of Physicians & Surgeons at Columbia University before embarking on her research career. Dr. Steinberg’s research focuses on signal transduction pathways that contribute to cardiac injury and stress-induced pathologic cardiac remodeling. Her studies have resulted in major advances in our understanding of functionally important post-translational processing events that underlie signaling diversity for cardiac beta1-adrenergic receptors and for key downstream signaling kinases. She has published over 150 peer-reviewed manuscripts and reviews in high quality scientific journals, including Science, Cell, New England Journal of Medicine, Journal of Clinical Investigation, Circulation, and Circulation Research.
Dr. Steinberg has served as a standing member of CCHF, CVA, and the Program Project Grant Study Section at NIH and grant review panels at AHA, the Howard Hughes Medical Institute, and the European Research Council. She served on the editorial boards of Journal of Biological Chemistry, Circulation Research, American Journal of Physiology, and Journal of Molecular and Cellular Cardiology and is currently Associate Editor of the Journal of Cardiovascular Research. She served as council member for ISHR, she co-organized the AHA annual BCVS meeting in 2005, and she has been a member of the leadership, nominations, and the Katz Prize Selection Committee at AHA. She delivered the AHA Thomas Smith Memorial Lecture in 2019.
Alter S, Zimmer Ad, Park M, Gong J, Caliebe A, Fölster-Holst R, Torrelo A, Colmenero I, Steinberg SF, Fischer J. Telangiectasia - Ectodermal Dysplasia-Brachydactyly-Cardiac Anomaly-Syndrome is caused by de novo mutations in Protein Kinase D1. Human Genetics (in press), 2020.
Park M and Steinberg SF. Carvedilol prevents redox inactivation of cardiomyocyte β1-adrenergic receptors. JACC: Basic to Translational Science 3:521-532, 2018. Park M, Reddy GR, Wallukat G, Xiang YK, and Steinberg SF.
Steinberg SF. Beta1-adrenergic receptor regulation revisited: the role of the extracellular N-terminus. Circ Res Viewpoint 123:1199-1201, 2018.
Park M, Reddy GR, Wallukat G, Xiang YK, and Steinberg SF. β1-adrenergic receptor O-glycosylation regulates N-terminal cleavage and signaling responses in cardiomyocytes. Scientific reports 7:7890, 2017.
Gong J, Yao Y, Zhang P, Udayasuryan B, Komissarova E, Zhang F, Chen J Sivaramakrishnan S Van Eyk JE and Steinberg SF. The C2 domain and altered ATP-binding loop phosphorylation at Ser357 mediate the redox-dependent increase in protein kinase C-delta activity. Mol Cell Biol 35:1727-1740, 2015.
Rybin VO, Guo J, Harleton E, Zhang F and Steinberg SF. Regulatory determinants that control PKD1 activity. J Biol Chem 287:22609-22615 2012.
Guo J, Gertsberg Z, Ozgen N, and Steinberg SF. Protein kinase D isoforms are activated in an agonist-specific manner in cardiomyocytes. J Biol Chem 286:6500-6509, 2011.
Guo J, Gertsberg Z, Ozgen N and Steinberg SF. p66Shc links 1-adrenergic receptors to a ROS-dependent pathway that regulates AKT and FOXO3a phosphorylation in cardiomyocytes. Circ Res 104:660-669, 2009.