Victoria Ploplis

Victoria Ploplis

Biography

2002-present
Research Professor, University of Notre Dame
1998-present
Associate Director, W.M. Keck Center for Transgene Research
1998-2002
Research Associate Professor, University of Notre Dame
1993-1998
Assistant Staff, Cleveland Clinic Research Foundation
1984-1993
Senior Scientist and Director of Cardiovascular Research, American Biogenetic Sciences, Inc.
1982-1984
Postdoctoral Researcher, University of Notre Dame and Scripps Research Institute
1981
Ph.D. in Biochemistry, University of Notre Dame
1975
B.A. in Biology and Chemistry, Rosary College

Selected Awards

1998-present
Fellow, Council on Atherosclerosis, Thrombosis, and Vascular Biology (American Heart Association)
1996-1997
James A. Shannon NIH Director's Award
1981-1982
John Hickam Fellow, American Heart Association (Indiana Affiliate)

Research Interests

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.

Recent Papers

  • Qiu, C., Yuan, Y., Zajicek, J., Liang, Z., Balsara, R.D., Brito-Robionson, T., Lee, S.W., Ploplis, V.A., Castellino, F.J. "Contributions of different modules of the plasminogen-binding Streptococcus pyogenes M-protein that mediate its functional dimerization" 2018 Journal of Structural Biology, 204 (2), pp. 151-164. DOI: 10.1016/j.jsb.2018.07.017
  • Flaherty, R.A., Donahue, D.L., Carothers, K.E., Ross, J.N., Ploplis, V.A., Castellino, F.J., Lee, S.W. "Neutralization of Streptolysin S-dependent and independent inflammatory cytokine IL-1β activity reduces pathology during early Group A Streptococcal skin infection" 2018 Frontiers in Cellular and Infection Microbiology, 8 (JUL), 211. DOI: 10.3389/fcimb.2018.00211
  • Liang, Z., Stephens, M., Ploplis, V.A., Lee, S.W., Castellino, F.J. "Draft genome sequences of six skin isolates of Streptococcus pyogenes" 2018 Genome Announcements, 6 (26), e00592-18. DOI: 10.1128/genomeA.00592-18
  • Fields, F.R., Carothers, K.E., Balsara, R.D., Ploplis, V.A., Castellino, F.J., Lee, S.W. "Rational design of syn-safencin, a novel linear antimicrobial peptide derived from the circular bacteriocin safencin AS-48" 2018 Journal of Antibiotics, 71 (6), pp. 592-600. DOI: 10.1038/s41429-018-0032-4
  • Miyajima, C., Iwaki, T., Umemura, K., Ploplis, V.A., Castellino, F.J. "Characterization of Atherosclerosis Formation in a Murine Model of Type IIa Human Familial Hypercholesterolemia" 2018 BioMed Research International, 1878964. DOI: 10.1155/2018/1878964
  • Gupta, K.K., Donahue, D.L., Sandoval-Cooper, M.J., Castellino, F.J., Ploplis, V.A.​​​​​​​ "Plasminogen Activator Inhibitor-1 Protects Mice Against Cardiac Fibrosis by Inhibiting Urokinase-type Plasminogen Activator-mediated Plasminogen Activation" 2017 Scientific Reports, 7 (1), 365. DOI: 10.1038/s41598-017-00418-y

Contact Information

  • Research Professor; Associate Director, W.M. Keck Center for Transgene Research
  • Office: 230B Raclin-Carmichael Hall
  • Phone: 574-631-4017
  • Send an email

Primary Research Areas

Research Specialties