Associate Director
Research Professor, Department of Chemistry and Biochemistry
University of Notre Dame
Adjunct Professor, Department of Biochemistry and Molecular Biology
Indiana University School of Medicine, South Bend, Indiana
Education
BA, Rosary College, 1975
PhD, University of Notre Dame, 1981
Postdoctoral fellow, Scripps Research Institute, 1982-1984
Address
W. M. Keck Center for Transgene Research
230 Raclin-Carmichael Hall
University of Notre Dame
Notre Dame, IN 46556
Contact
Phone: (574) 631-4017
Fax: (574) 631-4414
E-mail: vploplis@nd.edu
Honors and Awards
1975 BA, Summa Cum Laude
1975 Kappa Gamma Pi; National Catholic College Women’s Honor Society
1981-1982 John Hickam Fellow, American Heart Association (Indiana Affiliate)
1996-1997 James A. Shannon NIH Director’s Award
Memberships and Committees
1998 Elected fellow, Council on Atherosclerosis, Thrombosis, and Vascular Biology (American Heart Association)
2005 University Committee on Research and Sponsored Programs
Other Activities
2002 Associate Editor, Current Drug Targets
2005 NIH study section (HT) regular member
2006 American Heart Association study section member (Vascular Biology 2)
Research Focus
The fibrinolytic system is composed of the zymogen, plasminogen (Pg); its active enzyme (Pm); the plasminogen activators, tissue plasminogen activator (tPA) and urokinase (uPA); and relevant inhibitors plasminogen activator inhibitor-1 (PAI-1) and a2-antiplasmin. This system has been implicated in playing a pivotal role in numerous physiological processes. Due to the ability of plasmin to degrade fibrin, the fibrinolytic system plays an essential role in the prevention of thrombosis and maintenance of vascular patency. The ability of plasmin to directly degrade matrix protein, to activate other matrix degrading proteases and the existence of cellular receptors for components of the fibrinolytic system also implicates this pathway in localized proteolytic processes involved in normal cell migration, tissue remodeling, wound healing and angiogenesis. In addition, it's believed that the fibrinolytic system is involved in pathological processes where uncontrolled expression of proteolytic activity occurs, viz., tumor invasion and metastasis. However, much of the evidence for these diverse roles is surmised from in vitro studies and lack firm biological confirmation. Studies utilizing mice deficient for components of this pathway already have begun to challenge a number of the perceived roles of the fibrinolytic system. In addition, the lack of a more severe thrombotic phenotype and the occurrence of delayed clot lysis in mice deficient for Pg (PG-/-), would appear to support involvement of nonplasmin mediated fibrinolytic processes for maintaining some degree of vascular patency and most probably survival in these deficient mice, possibly due to leukocyte elastases.
Utilizing mice deficient for components of the fibrinolytic system, our laboratory is currently testing hypothesized functions of this pathway when physiologically challenged. Specifically, we are assessing its' role in inflammation and diseases associated with inflammation, viz., asthma, atherosclerosis, pulmonary fibrosis as well as other physiological and pathophysiological processes in which cell migration is an essential event, viz., tumor growth, metastasis and angiogenesis. Additionally, we are isolating primary arterial and venous endothelial cells from these gene deficient mice in order to determine altered endothelial cell functions that may contribute to changes in angiogenesis.
Selected Recent Publications
Guillen-Ahlers H, Buechler SA, Suckow MA, Castellino FJ, Ploplis VA. (2008). Sulindac treatment alters collagen and matrilysin expression in adenomas of ApcMin/+ mice. Carcinogenesis. 29:1421-1427.
Ploplis VA, Tipton H, Menchen H, Castellino FJ. (2007). A urokinase-type plasminogen activator deficiency diminishes the frequency of intestinal adenomas in ApcMin/+ mice. J Pathol. 213:266-274.
Balsara RD, Xu Z, Ploplis VA. (2007). Targeting plasminogen activator inhibitor-1: Role in cell signaling and the biology of domain-specific knock-in mice. Current Drug Targets. 8:982-995.
Castellino FJ, Ganopolsky JG, Noria F Sandoval-Cooper MJ, Ploplis VA. (2006). Focal arterial inflammation is augmented in mice with a deficiency of the protein C gene. Thromb Haemost. 96:794-801.
Balsara RD, Castellino FJ, Ploplis VA. (2006). A novel function of PAI-1 in modulation of the Akt pathway in wild-type and PAI-1-deficient endothelial cells. J Biol Chem. 281:22527-22536.
Iwaki Y, Sandoval-Cooper MJ, Brechmann M, Ploplis VA, Castellino FJ. (2006). A fibrinogen deficiency accelerates the initiation of LDL-cholesterol-driven atherosclerosis via thrombin generation and platelet activation in genetically-predisposed mice. Blood. 107:3883-3891.
Kwak S-H, Wang X-Q, He Q., Sohn J-W, Mitra S, Bdeir K, Xu Z., Ploplis VA, Idell S, Cines D, Abraham E. (2006). Plasminogen activation inhibitor-1 potentiates LPS-induced neutrophil activation through a JNK-mediated pathway. Thrombosis and Hemostasis. 95:829-835.
Castellino FJ, Ploplis VA. (2005). Structure and function of the plasminogen/plasmin system. Thromb Haemost. 93:647-654.
Xu Z, Balsara R, Gorlatova NV, Lawrence DA, Castellino FJ, Ploplis VA.. (2004). Conservation of critical functional domains in murine plasminogen activator inhibitor-1. J Biol Chem. 279:17914-17920.
Ploplis VA, Balsara R, Sandoval-Cooper MJ, Yin ZJ, Batten J, Modi, N, Gaduoa D, Donahue DL, Martin JA, Castellino FJ. (2004). Enhanced in vitro proliferation of aortic endothelial cells from PAI-1-/- mice. J Biol Chem. 279:6143-6151.
Busuttil SJ, Ploplis VA, Castellino FJ, Tang L, Eaton JW, Plow EF. (2004). A central role for plasminogen in the inflammatory response to biomaterials. J Thromb Haemost. 2:1798-1805.
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