Dr. Ploplis received her B.A. degree in biology/chemistry in 1975 from Rosary College and her Ph.D. in biochemistry in 1981 from the University of Notre Dame. She conducted postdoctoral research at the University of Notre Dame, then at Scripps Research Institute from 1982 to 1984. Subsequently, Dr. Ploplis was senior scientist and director of cardiovascular research at American Biogenetic Sciences, Inc. (1984-1994), and assistant staff at the Cleveland Clinic Research Foundation (1994-1998). She joined the faculty of the University of Notre Dame in 1998. She is currently an elected fellow on the American Heart Association Council on Atherosclerosis, Thrombosis, and Vascular Biology.
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.
- Yasui, H.; Donahue, D.L.; Walsh, M.; Castellino, F.J.; Ploplis, V.A. "Early coagulation events induce acute lung injury in a rat model of blunt traumatic brain injury." Am. J. Physiol.-Lung C. 2016, 311(1), L74-L86.
- Bao, Y.J.; Liang, Z.; Mayfield, J.A.; Donahue, D.L.; Carothers, K.E.; Lee, S.W.; Ploplis, V.A.; Castellino, F.J. "Genomic Characterization of a Pattern D Streptococcus pyogenes emm53 Isolate Reveals a Genetic Rationale for Invasive Skin Tropicity." J. Bacteriol. 2016, 198(12), 1712-1724.
- Mamczak, C.N.; Maloney, M.; Fritz, B.; Boyer, B.; Thomas, S.; Evans, E.; Ploplis, V.A.; Castellino, F.J.; McCollester, J.; Walsh, M. "Thromboelastography in Orthopaedic Trauma Acute Pelvic Fracture Resuscitation: A Descriptive Pilot Study." J. Orthop. Trauma 2016, 30(6), 299-305.
- Agrahari, G.; Liang, Z.; Glinton, K.; Lee, S.W.; Ploplis, V.A.; Castellino, F.J. "Streptococcus pyogenes Employs Strain-dependent Mechanisms of C3b Inactivation to Inhibit Phagocytosis and Killing of Bacteria." J. Biol. Chem. 2016, 291(17), 9181-9189.
- Walsh, M.; Fritz, S.; Hake, D.; Son, M.; Greve, S.; Jbara, M.; Chitta, S.; Fritz, B.; Miller, A.; Bader, M.K.; McCollester, J.; Binz, S.; Liew-Spilger, A.; Thomas, S.; Crepinsek, A.; Shariff, F.; Ploplis, V.; Castellino, F.J. "Targeted Thromboelastographic (TEG) Blood Component and Pharmacologic Hemostatic Therapy in Traumatic and Acquired Coagulopathy." Curr. Drug Targets 2016, 17(8), 954-970.
- Bao, Y.J.; Liang, Z.; Mayfield, J.A.; Lee, S.W.; Ploplis, V.A.; Castellino, F.J. "CovRS-Regulated Transcriptome Analysis of a Hypervirulent M23 Strain of Group A Streptococcus pyogenes Provides New Insights into Virulence Determinants." J. Bacteriol. 2015, 197(19), 3191-3205.