Victoria Ploplis

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.

Selected Publications

• Charles, J.; McCann, N.; Ploplis, V. A. and Castellino, F. J. "Spike Protein Receptor-Binding Domains from SARS-CoV-2 Variants of Interest Bind Human ACE2 More Tightly than the Prototype Spike Protein" 2023 Biochemical and Biophysical Research Communications, 641, pp.61-66. DOI: 10.1016/j.bbrc.2022.12.011.
• Hammers, D. E.; Donahue, D. L.; Tucker, Z. D.; Ashfeld, B. L.; Ploplis, V. A.; Castellino, F. J. and Lee, S. W. "Streptolysin S Targets the Sodium-Bicarbonate Cotransporter NBCn1 to Induce Inflammation and Cytotoxicity in Human Keratinocytes during Group A Streptococcal Infection" 2022 Frontiers in Cellular and Infection Microbiology, 12, 1002230. DOI: 10.3389/fcimb.2022.1002230.
• Readnour, B. M.; Ayinuola, Y. A.; Russo, B. T.; Liang, Z.; Lee, S. W.; Ploplis, V. A.; Fischetti, V. A. and Castellino, F. J. "Evolution of Streptococcus Pyogenes has Maximized the Efficiency of the Sortase A Cleavage Motif for Cell Wall Transpeptidation" 2022 Journal of Biological Chemistry, 298 (6), 101940. DOI: 10.1016/j.jbc.2022.101940.
• Charles, J. and Ploplis, V. A. "COVID-19 Induces Cytokine Storm and Dysfunctional Hemostasis" 2022 Current Drug Targets, 23 (17), pp.1603-1610. DOI: 10.2174/1389450124666221025102929.
• 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.