Dr. Berk's laboratory has focused on defining the mechanisms by which cells in the vascular wall respond to hemodynamic and hormonal stimuli. In particular the laboratory has studied the role of protein kinases as mediators of signal transduction in the vasculature. The four major research projects ongoing in the laboratory include 1) Mechanisms by which blood vessels sense changes in blood flow and modulate vessel size and tone. Using cultured endothelial cells and animal models of altered blood flow; signal transduction events that confer atheroprotection in the setting of steady laminar flow are being investigated. The goal is to characterize novel biomechanical sensing molecules. 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 antioxidant vitamins such as vitamin C and E work to prevent ischemic heart disease. 4) A genetic model of vascular remodeling in the rat 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 rats.

Dr. Berk's goals as Chief of Cardiology are to expand and develop new clinical services for patients with cardiovascular disease while strengthening research programs to advance the understanding and therapy of cardiovascular disease. Clinical efforts include development of a Cardiovascular Service Line, initiation of a Left Ventricular Assist Device Program, outreach efforts for primary and secondary prevention, and development of an outcomes research program. Basic research will grow as a result of recruitment of new faculty to the Center for Cardiovascular Research, one of the six new Aab Institute of Biomedical Sciences (Aab) programs. Eight cardiovascular researchers are being recruited to 15,000 square feet of wet lab space in the new Medical Research Building. Areas of research will include vascular biology, signal transduction, genetic approaches to ischemic heart disease, blood vessel development, angiogenesis and transgenic mouse models of cardiovascular disease.

1999, ASH Specialists Program, ASH Specialist in Clinical Hypertension

1999, Borun Visiting Professor in Cardiology, UCLA Medical Center, Los Angeles, CA

Tanimoto T, Jin Z, Berk BC. Transactivation of vascular endothelial growth factor (VEGF) receptor Flk-1/KDR is involved in sphingosine 1-phosphate-stimulated phosphorylation of Akt and endothelial nitric-oxide synthase (eNOS). J Biol Chem, 2002;277:42997-43001.

Abe J, Berk BC. Hypoxia and HIF-1alpha stability: another stress-sensing mechanism for Shc. Circ Res, 2002;91:4-6.

Huang Q, Lerner-Marmarosh N, Che W, Ohta S, Osawa M, Yoshizumi M, Glassman M, Yan C, Berk BC, Abe J. The novel role of C-terminal region of SHP-2: involvement of Gab1 and SHP-2 phosphatase activity in Elk-1 activation. J Biol Chem; 2002;227:29330-29341.

Surapisitchat J, Hoefen RJ, Pi X, Yoshizumi M, Yan C, Berk BC. Fluid shear stress inhibits TNF-alpha activation of JNK but not ERK1/2 or p38 in human umbilical vein endothelial cells: Inhibitory crosstalk among MAPK family members. Proc Natl Acad Sci, 2001;98:6476-6481.

Yan C, Luo H, Lee JD, Abe J, Berk BC. Molecular Cloning of Mouse ERK5/BMK1 Splice Variants and Characterization of ERK5 Functional Domains. J Biol Chem, 2001;276:10870-10878.