Victoria A. Ploplis, PhD

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)

Other Activities
2002 - Present  Associate Editor, Current Drug Targets
2005 - 2009  NIH study section (HT) regular member

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

Balsara RD, Merryman R, Virjee F, Northway C, Castellino FJ, Ploplis VA. (2011). A deficiency of uPAR alters endothelial angiogenic function and cell morphology. Vasc Cell. 2:3:10.

Castellino FJ, Donahue DL, Navari RM, Ploplis VA, Walsh M.  (2011).  An accompanying genetic severe deficiency of tissue factor protects mice with a protein C deficiency from lethal endotoxemia.  Blood.  117: 283-289

Iwaki T, Malinverno C, Smith D, Xu Z, Liang Z, Ploplis VA, Castellino FJ. (2010). The generation and characterization of mice expressing a plasmin-inactivating actie site mutation.  J Thromb Haemost. 8: 2341-2344.

Xu Z, Xu H, Ploplis VA, Castellino FJ. (2010).  Factor VII deficiency impairs cutaneous wound healing in mice.  Mol Med. 16:167-176

Guillen-Ahlers H, Suckow MA, Castellino FJ, Ploplis VA.  (2010).  Fas/CD95 deficiency in ApcMin/+mice increases intestinal tumor burden. PLoS One. 5:e9070

Danese S, Vetrano S, Zhang L, Ploplis VA, Castellino FJ.  (2010)  The protein C pathway in tissue inflammation and injury: pathogenic role and therapeutic implications.  Blood.  115:1121-1130.

Xu Z, Castellino FJ, Ploplis VA.  (2010). Plasminogen activator inhibitor-1 (PAI-1) is cardioprotective in mice by maintaining microvascular integrity and cardiac architecture. Blood. 115:2038-2047.

Castellino FJ, Ploplis VA.  (2009).  The protein C pathway and pathologic processes.  J Thromb Haemost  7 Suppl 1:140-145

Shinagawa K, Ploplis VA, Castellino FJ.  (2009).  A severe deficiency of coagulation factor VIIa results in attenuation of the asthmatic response in mice.  Am J Physiol Lung Cell Mol Physiol. 296:L763-770.

Tang H, Fu Y, Lei Q, Han Q, Ploplis VA, Castellino FJ, Li L, Luo Y.  (2009).  Fibrinogen facilitates the anti-tumor effect of nonnative endostatin.  Biochem Biophys Res Commun. 380:249-253.

Tang H, Fu Y, Cui Y, He Y, Zeng X, Ploplis VA, Castellino FJ, Luo Y. (2009).  Fibrinogen has chaperone-like activity.  Biochem Biophys Res Commun. 16;378:662-667.