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 Eugene A. Sprague, Ph.D.Julio C Palmaz Professor of Radiology Department of Radiology
Educational Background:
Areas of Research Interest: The overall field of research interest in this laboratory is vascular biology with particular emphasis onendothelial biology. Our efforts are currently directed toward exploring the influence of specific flow environments on the endothelial cellular and molecular mechanisms mediating key elements related to atherogenesis and restenosis at sites of stent revascularization. We are especially interested in the influence of low shear, reversing flow patterns as an important co-initiating factor in early atherogenesis as well as micro-flow disturbances around stent struts that may contribute to stent restenosis. These studies involve examining gene expression and cell surface expression or secretion of these molecules as well as examining the signaling mechanisms involved in transducing the mechanical stimulus of flow into these specific cellular and molecular responses. Our efforts within area 2 overlap with efforts within area 1 but are targeted toward examining how the flow dynamics at sites of vascular intervention (atherosclerotic lesion sites) may influence the progression of restenosis at these sites. We are especially interested in promoting early reendothelialization of these sites. Additionally, ongoing efforts are investigating the influence of different biomaterials on key factors involved in restenosis including inflammation, thombosis, and re-endothelialization. We have recently developed and published (in press) a model system for evaluating biocompatibility of potential vascular biomaterial surfaces. Also, we have ongoing research examining biomaterial surface chemistry at the atomic level using state-of-the art analytic technology, XPS and time-of-flight SIMS. As a complement to these surface chemistry approaches, this laboratory employs atomic force microscopy to examine biomaterial surfaces at the nanometer level. In area 3, ongoing studies are based on the concept that increasing the rate of of re-endothelialization at stent implantation sites can limit restenosis at these sites and eliminate the need for using drugs to limit restenosis. We are examining the influence of flow dynamics on endothelial cell migration on to implanted vascular materials, the effect of surface micro- and nano-patterning on endothelialization of vascular biomaterials, and the influence of different biomaterials on endothelialization. Our efforts in area four have only recently been initiated but involve the use of some novel biomaterials and a unique design. Selected Publications: Sprague EA. In vivo cardiovascular assays for drug discovery: Evolution of drug-eluting stent. Current Opinion in Investigational Drugs, 2007;8(3):219-225. Zhang BX, Ma X, Zhang WK, Yeh CK, Lin A, Luo J, Sprague EA, Swerdlow RH, Katz MS. Polyunsaturated fatty acids mobilize intracellular Ca2+ in NT2 human teratocarcinoma cells by causing release of Ca2+ from mitochondria. Am J Physiol Cell Physiol, 2006;290(5):1321-1333. Sprague EA. In vivo cardiovascular assays for drug discovery: evolution of the drug-eluting stent. Curr Opin Investig Drugs. 2007 Mar;8(3):219-25. Sprague EA, Palmaz JC. A model system to assess key vascular responses to biomaterials. J Endovasc Ther. 2005 Oct;12(5):594-604. Priscilla P. Cherian, Arlene J. Siller-Jackson, Sumin Gu, Xin Wang, Lynda F. Bonewald, Eugene Sprague, and Jean X. Jiang. Mechanical Strain Opens Connexin 43 Hemichannels in Osteocytes: A Novel Mechanism for the Release of Prostaglandin. Mol Biol Cell 16, 3100-3106 , 2005. Mohan S, Hamuro M, Sorescu GP, Koyoma K, Sprague EA, Jo H, Valente AJ, Prihoda TJ, Natarajan M. IkB-a-dependent regulation of low shear flow induced NF-kB activity: Role of Nitric Oxide. American Journal of Physiology: Cell Physiology 284:C1039-1047, 2003. Hamuro M, Palmaz JC, Sprague EA, Fuss C, Luo J: Influence of stent edge angle on endothelialization in an in vitro model. J Vasc Interv Radiol 12: 607-611, 2001. Mohan S, Mohan N, Valente AJ, Sprague EA: Regulation of low shear flow-induced HAEC VCAM-1 expression and monocyte adhesion. Am. J. Physiol. 276 (Cell Physiol. 45): C1100-C1107, 1999. Sprague EA, Mohan S., Nerem RM. Shear Stress regulation of Monocyte/endothelial cell interactions. J. Vasc. Surg. 29:1138-1140, 1999. Sprague EA, Luo J, Palmaz JC: Human aortic endothelial cell migration onto stent surfaces under static and flow conditions. JVIR 8:83-92,1997. Prasad, A.R.S., Logan. S.A., Nerem, R.M., Schwartz, C.J., and Sprague, E.A. Flow related responses of intracellular inositol phosphate levels in cultured aortic endothelial cells .Circ Res 72:827-836, 1993. Contact Information: University of Texas Health Science Center Phone: 210-567-5564 Fax: 210-567-5541 sprague@uthscsa.edu
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