Victoria Ploplis

Victoria Ploplis


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

Selected Awards

Fellow, Council on Atherosclerosis, Thrombosis, and Vascular Biology (American Heart Association)
James A. Shannon NIH Director's Award
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 Publications

  • Ayinuola, Y. A.; Tjia-Fleck, S.; Readnour, B. M.; Liang, Z.; Ayinuola, O.; Paul, L. N.; Lee, S.; Fischetti, V. A.; Ploplis, V. A. and Castellino, F. J. "Relationships between Plasminogen-Binding M-Protein and Surface Enolase for Human Plasminogen Acquisition and Activation in Streptococcus Pyogenes" 2022 Frontiers in Microbiology, 13, 905670. DOI: 10.3389/fmicb.2022.905670.
  • Iwaki, T.; Arakawa, T.; Sandoval-Cooper, M. J.; Smith, D. L.; Donahue, D.; Ploplis, V. A.; Umemura, K. and Castellino, F. J. "Plasminogen Deficiency significantly Reduces Vascular Wall Disease in a Murine Model of Type IIa Hypercholesterolemia" 2021 Biomedicines, 9 (12), 1832. DOI: 10.3390/biomedicines9121832.
  • Ayinuola, O.; Ayinuola, Y. A.; Qiu, C. J.; Lee, S. W.; Ploplis, V. A. and Castellino, F. J. "Binding of the Kringle-2 Domain of Human Plasminogen to Streptococcal PAM-Type M-Protein Causes Dissociation of PAM Dimers" 2021 Microbiologyopen, 10 (6), e1252. DOI: 10.1002/mbo3.1252.
  • Vu, H. M.; Hammers, D. E.; Liang, Z.; Nguyen, G. L.; Benz, M. E.; Moran, T. E.; Higashi, D. L.; Park, C. J.; Ayinuola, Y. A.; Donahue, D. L.; Flores-Mireles, A. L.; Ploplis, V. A.; Castellino, F. J. and Lee, S. W. "Group A Streptococcus-Induced Activation of Human Plasminogen is Required for Keratinocyte Wound Retraction and Rapid Clot Dissolution" 2021 Frontiers in Cardiovascular Medicine, 8, 667554. DOI: 10.3389/fcvm.2021.667554.
  • Ayinuola, Y. A.; Brito-Robinson, T.; Ayinuola, O.; Beck, J. E.; Cruz-Topete, D.; Lee, S. W.; Ploplis, V. A. and Castellino, F. J. "Streptococcus Co-Opts a Conformational Lock in Human Plasminogen to Facilitate Streptokinase Cleavage and Bacterial Virulence" 2021 Journal of Biological Chemistry, 296, 100099. DOI: 10.1074/jbc.RA120.016262.
  • Fields, F. R.; Manzo, G.; Hind, C. K.; Janardhanan, J.; Foik, I. P.; Silva, P. D.; Balsara, R. D.; Clifford, M.; Vu, H. M.; Ross, J. N.; Kalwajtys, V. R.; Gonzalez, A. J.; Bui, T. T.; Ploplis, V. A.; Castellino, F. J.; Siryaporn, A.; Chang, M.; Sutton, J. M.; Mason, A. J. and Lee, S. "Synthetic Antimicrobial Peptide Tuning Permits Membrane Disruption and Interpeptide Synergy" 2020 ACS Pharmacology & Translational Science, 3 (3), pp.418-424. DOI: 10.1021/acsptsci.0c00001.


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