Bradford C. Berk, M.D., Ph.D.
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Bradford C. Berk, M.D., Ph.D.Senior Vice President for Health Sciences and CEO Current AppointmentsCEO, Medical Center and Strong Health University of Rochester
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Research
- Vascular Smooth Muscle Cell Na+/H+ Exchange;
- Molecular Biology of the Renin-Angiotensin System
- Regulation of Endothelial Cell Function: Anti-inflammatory Mechanisms
- Flow-mediated Signal Transduction in Endothelial Cells
- Role of Oxidative Stress in Vascular Injury and Atherogenesis
- Genetic analysis of vascular remodeling
Research Overview
Dr. Berk's laboratory is known for studying signal transduction mechanisms in the vasculature, focusing specifically on defining the mechanisms by which cells in the vascular wall respond to hemodynamic and hormonal stimuli. The four major research areas ongoing in the laboratory include 1) Mechanisms by which blood vessels sense changes in blood flow using protein kinases as targets for signal events. Using cultured endothelial cells and animal models of altered blood flow two projects are underway. The first project investigates the mechanisms by which flow activates the Big MAP kinase (or ERK5) and inhibits inflammation and atherosclerosis. In the second project, the redox-dependent mechanisms that maintain an antioxidant environment are being studied using the apoptosis signal kinase-1 (ASK1) and thioredoxin as targets. The goal of these projects is to identify signal transduction events that confer atheroprotection in the setting of steady laminar flow as opposed to the pro-atherosclerotic effects of disturbed and turbulent flow. 2) The cellular mechanisms that cause hypertension are being investigated by analysis of the role of the renin angiotensin system and the kinases that regulate intracellular sodium. The regulation of smooth muscle cell growth by angiotensin II is focused on the activation of intracellular kinases and phosphatases by the angiotensin II receptor. 3) The mechanisms by which changes in cellular redox state alter blood vessel function are being studied to provide insight into the ways that reactive oxygen species regulate vessel function. Specifically the role of the chaperone molecule cyclophilin A as a mediator of vascular pathology is being studied with several different transgenic models. 4) A genetic model of vascular remodeling in the mouse has been established. A carotid flow reduction model has been characterized and is being used to identify genes responsible for impaired flow-dependent remodeling by positional cloning in inbred strains of mice.
Recent Awards & Honors
2003 Russell Ross Memorial Lectureship in Vascular Biology, Council for Arteriosclerosis, Thrombosis, Vascular Biology.
2004-05 Vice-chair, Vascular Cell Biology Gordon conference.
Recent Publications
- Yamawaki H, Haendeler J, Berk BC. Thioredoxin: a key regulator of cardiovascular homeostasis. Circ Res. 2003;93:1029-33.
- Pi X, Yan C, Berk BC. Big mitogen-activated protein kinase (BMK1)/ERK5 protects endothelial cells from apoptosis. Circ Res. 2004;94:362-369.
- Zheng Q, Yin G, Yan C, Cavet M, Berk BC. 14-3-3beta binds to big mitogen-activated protein kinase 1 (BMK1/ERK5) and regulates BMK1 function. J Biol Chem. 2004;279:8787-8791.
- Yin G, Haendeler J, Yan C, Berk BC. GIT1 functions as a scaffold for MEK1-extracellular signal-regulated kinase 1 and 2 activation by angiotensin II and epidermal growth factor, Mol Cell Biol. 2004;24:875-85.
- van nieuw Amerongen GP, Natarajan K, Yin G, Hoefen RJ, Osawa M, Haendeler J, Ridley AJ, Fujiwara K, Van Hinsbergh VWM, Berk BC. GIT1 mediates thrombin signaling in endothelial cells. Role in turnover of RhoA-type focal adhesions. Circ Res. 2004;94:1041-1049.
- Konishi A, Aizawa T, Mohan A, Korshunov VA, Berk BC. Hydrogen peroxide activates the Gas6-Axl pathway in vascular smooth muscle cells. J Biol Chem. 2004; 279(27):28766-28770.
- Korshunov VA, Berk BC. Strain-dependent vascular remodeling. The “Glagov Phenomenon” is genetically determined. Circulation, 2004;110:220-226.