David S. Weber, Ph.D.
 Assistant Professor 

Ph.D., Physiology, Medical College of Wisconsin.

Postdoctoral Studies: 
Division of Cardiology, Emory University, Georgia.
Department of Physiology,
Medical College of Georgia and University of Michigan Medical School.

Research Interests:  

Oxidative stress, defined as an increase in reactive oxygen species (ROS) in the vasculature, has been implicated in several pathologic conditions affecting the cardiovascular system including hypertension, athlerosclerosis, and restenosis following balloon injury. Each of these conditions is associated with significant vascular damage and repair. Adjacent normal tissue facilitates the repair process and formation of neointima by both proliferation and migration. Several growth factors, including the potent platelet-derived growth factor (PDGF), stimulate vascular smooth muscle cell (VSMC) migration from the media to the neointima. Exposure of vascular smooth muscle cells to PDGF also results in generation of ROS, and ROS have been shown to have significant effects on both the growth and migration of vascular smooth muscle cells.

Therefore, the focus of my current studies is to test the hypothesis that ROS are critical mediators of VSMC migration. Two specific aims are being addressed; 1) to define signaling steps that mediate PDGF-induced VSMC migration and determine which are ROS sensitive, and 2) to define the contribution of ROS in vivo by studying migration and remodeling during restenosis following vascular injury in transgenic mice producing altered levels of ROS. These studies utilize several techniques including 1) the use of transwell migration assays using cultured VSMC following pharmacological interventions to examine mediators of migration, 2) immunoblotting, immunoprecipitation, and activity assays in cultured VSMC following pharmacological intervention or adenoviral infection to determine the redox-sensitivity of signaling mechanisms associated with migration, and 3) the use of transgenic mice that have VSMC-specific alterations in ROS levels to study the redox-sensitivity of signaling mechanisms during the process of restenosis induced by wire injury of the femoral artery.

Recent Publications:

Weber, D.S., J.C. Frisbee, and J.H Lombard. Effect of short term and chronic high salt diets on the responses of resistance arteries and arterioles to vasoconstrictors.  Microvascular Research 57:310-319, 1999.

Frisbee, J.C., D.S. Weber, J.H. Lombard. Chronic captopril administration decreases vasodilator responses in skeletal muscle arterioles.  Am J Hypertens 12:705-715, 1999.  

Weber, D.S. and J.H. Lombard.  Elevated salt intake impairs dilation of rat skeletal muscle resistance arteries via angiotensin II suppression.  Am J Physiol 278:H500-H506, 2000.

Frisbee, J.C., D. S. Weber, Y. Liu, J.A. DeBruin, and J.H. Lombard. Altered structure and mechanics of rat skeletal muscle resistance arteries with high salt diet and reduced renal mass hypertension. Microvascular Research 59:323-329, 2000.

 Johns, D.G., A.M. Dorrance, R. Leite, D.S. Weber, and R.C. Webb.  Novel mechanisms contributing to vascular changes in hypertension. (review) J Biomed Sci  7(6):431-443, 2000.

 Weber, D.S. and R.C. Webb.  Enhanced relaxation of the Rho-kinase inhibitor Y-27632 in mineralocorticoid hypertensive rats. Pharmacology 63:129-133, 2001.  

Weber, D.S. and J.H. Lombard.  Angiotensin II AT1 receptors preserve vasodilator reactivity in skeletal muscle resistance arteries.  Amer J Physiol. 280:H2196-H2202, 2001.

 Chitaley K, D. Weber, and R.C. Webb. RhoA/Rho-kinase, vasacular changes and hypertension (review). Curr Hypertens Rep 3(2):139-44, 2001.

 Seshiah, P.N., D.S Weber, P Rocic, L. Valppu, Y. Taniyama, and K.K. Griendling.  Angiotensin II stimulation of NAD(P)H oxidase activity: upstream mediators. Circ Res  91(5):406-13, 2002.

 Weber, D.S. and K.K. Griendling.  The Yin/Yang of superoxide dismutase mimetics: potential cardiovascular therapies? Brit J Pharm 139:1059-1060, 2003.

 Taniyama, Y., D.S Weber, P. Rocic, L.Hilenski, M.L. Akers, J. Park, B.A. Hemmings, R.W. Alexander, and K.K. Griendling.  Pyk2-and Src-dependent tyrosine phosphorylation of PDK1 regulates focal adhesions.  Mol Cell Biol. 23:8019-29, 2003

 Weber, D.S. and K.K. Griendling. Thrombin: Beyond coagulation. J Mol Cell Cardiol 36:13-15, 2004.

 Weber, D.S., Y. Taniyama, P. Rocic, P.N. Seshiah, M.A. Dechert, W.T. Gerthoffer, and K.K. Griendling PDK1 and PAK mediate reactive oxygen species dependent regulation of PDGF-induced smooth muscle cell migration.  Circ Res 94:1219-1226, 2004.

 Taniyama, Y., M.Ushio-Fukai, P. Rocic, M.J. Kingsley, H. Hitomi, C. Pfahnl, D.S. Weber, R. W. Alexander, and K.K. Griendling. Role of p38MAPK and MAPKAPK-2 in angiotensin II-induced Akt activation in vascular smooth muscle cells.  Am J Physiol Cell Physiol 287: C494-C499, 2004.

 Weber, D.S., P. Rocic, A.M. Mellis, A.N. Lyle, D.G. Harrison, and K.K. Griendling.  Angiotensin II-induced hypertrophy is potentiated in mice overexpressing p22^phox in vascular smooth muscle.  (in press, Am J Physiol Heart Circ Physiol 288: H37-H42, 2005.

 Laude, K., H. Cai, B. Fink, ,N. Hoch, D.S. Weber, L. McCann, G. Kojda, T. Fukai, S. Dikalov, S. Ramasamy, G. Gamez, K.K. Griendling, and D.G. Harrison.  Hemodynamic and biochemical adaptations to chronic vascular oxidant stress caused by vascular smooth muscle overexpression of p22^phox in mice. Am J Physiol Heart Circ Physiol 288: H7-H12, 2005.

 Dikalova A, B. Lassègue, R. Clempus, S. Dikalov, A. San Martin, A. Lyle, D.S. Weber, D. Weiss, W.R. Taylor, H.H. Schmidt, G. Cheng, G.K. Owens, D. Lambeth, , and K.K. Griendling. Nox1 overexpression potentiates angiotensin II-induced hypertension and vascular smooth muscle cell hypertrophy in transgenic mice. (in review, Circulation)

 Weber, D.S., A.E. Linder, L.G. D’Alecy and R.C. Webb. Altered vascular reactivity in mice made hypertensive by nitric oxide synthase inhibition. (in review, J Cardiovascular Pharm)

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