Victoria A Ploplis, PhD

Associate Director, Professor of Chemistry and Biochemistry

Victoria A - Ploplis, PhD

Contact Info

Phone: 574-631-8996
Email: vploplis@nd.edu

Biography

2002–present Research Professor, University of Notre Dame
1998–2002  Research Associate Professor, University of Notre Dame and Associate Director, W. M. Keck Center for Transgene Research
1993–1998 Assistant Staff, Cleveland Clinic Research Foundation
1984–1993 Senior Scientist and Director of Cardiovascular Research at American Biogenetic Sciences, Inc.
1982–1984 Postdoctoral Fellow, University of Notre Dame and Scripps Research Institute, La Jolla, CA.
1981 Ph.D., Biochemistry, University of Notre Dame

Honors & Awards 

1998–present Fellow, Council on Athersclerosis, Thrombosis, and Vascular biology (AHA)
1996–1997 James A. Shannon NIH Director’s Award
1981–1982 John Hickam Fellow, American Heart Association (Indiana Affiliate)
1975–present Kappa Gamma Pi; National Catholic College Women’s Honor Society
1975 B.A., Summa Cum Laude

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. 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, IBD, acute kidney injury due to sepsis, cardiac 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

Gupta KK, Donahue DL, Sandoval-Cooper MJ, Castellino FJ, Ploplis VA. Plasminogen Activator Inhibitor-1 Protects Mice Against Cardiac Fibrosis by Inhibiting Urokinase-type Plasminogen Activator-mediated Plasminogen Activation. Sci Rep. 2017 Mar 23;7(1):365. doi: 10.1038/s41598-017-00418-y. PMID: 28336948

Glinton K, Beck J, Liang Z, Qiu C, Lee SW, Ploplis VA, Castellino FJ. Variable Region in Streptococcal M-Proteins Provides Stable Binding with Host Fibrinogen for Plasminogen-Mediated Bacterial Invasion. J Biol Chem. 2017 Mar 9. pii: jbc.M116.768937. doi: 10.1074/jbc.M116.768937. [Epub ahead of print] PMID: 28280245

Walsh M, Shreve J, Thomas S, Moore E, Moore H, Hake D, Pohlman T, Davis P, Ploplis V, Piscoya A, Wegner J, Bryant J, Crepinsek A, Lantry J, Sheppard F, Castellino F. Fibrinolysis in Trauma: "Myth," "Reality," or "Something in Between". Semin Thromb Hemost. 2017 Mar;43(2):200-212. doi: 10.1055/s-0036-1597900. Epub 2017 Feb 20. PMID: 28219085

Bao YJ, Shapiro BJ, Lee SW, Ploplis VA, Castellino FJ. Phenotypic differentiation of Streptococcus pyogenes populations is induced by recombination-driven gene-specific sweeps. Sci Rep. 2016 Nov 8;6:36644. doi: 10.1038/srep36644. PMID: 27821851

Higashi DL, Biais N, Donahue DL, Mayfield JA, Tessier CR, Rodriguez K, Ashfeld BL, Luchetti J, Ploplis VA, Castellino FJ, Lee SW. Activation of band 3 mediates group A Streptococcus streptolysin S-based beta-haemolysis. Nat Microbiol. 2016 Jan 18;1:15004. doi: 10.1038/nmicrobiol.2015.4. PMID: 27571972

Bao YJ, Liang Z, Mayfield JA, McShan WM, Lee SW, Ploplis VA, Castellino FJ. Novel genomic rearrangements mediated by multiple genetic elements in Streptococcus pyogenes M23ND confer potential for evolutionary persistence. Microbiology. 2016 Aug;162(8):1346-59. doi: 10.1099/mic.0.000326. Epub 2016 Jun 21. PMID: 27329479

Gupta KK, Xu Z, Castellino FJ, Ploplis VA. Plasminogen activator inhibitor-1 stimulates macrophage activation through Toll-like Receptor-4. Biochem Biophys Res Commun. 2016 Aug 26;477(3):503-8. doi: 10.1016/j.bbrc.2016.06.065. Epub 2016 Jun 15. PMID: 27317488

Mamczak CN, Maloney M, Fritz B, Boyer B, Thomas S, Evans E, Ploplis VA, Castellino FJ, McCollester J, Walsh M. Thromboelastography in Orthopaedic Trauma Acute Pelvic Fracture Resuscitation: A Descriptive Pilot Study. J Orthop Trauma. 2016 Jun;30(6):299-305. doi: 10.1097/BOT.0000000000000537. PMID: 27206253

Yasui H, Donahue DL, Walsh M, Castellino FJ, Ploplis VA. Early coagulation events induce acute lung injury in a rat model of blunt traumatic brain injury. Am J Physiol Lung Cell Mol Physiol. 2016 Jul 1;311(1):L74-86. doi: 10.1152/ajplung.00429.2015. Epub 2016 May 17. PMID: 27190065

Bao YJ, Liang Z, Mayfield JA, Donahue DL, Carothers KE, Lee SW, Ploplis VA, Castellino FJ. Genomic Characterization of a Pattern D Streptococcus pyogenes emm53 Isolate Reveals a Genetic Rationale for Invasive Skin Tropicity. J Bacteriol. 2016 May 27;198(12):1712-24. doi: 10.1128/JB.01019-15. Print 2016 Jun 15. PMID: 27044623

Walsh M, Fritz S, Hake D, Son M, Greve S, Jbara M, Chitta S, Fritz B, Miller A, Bader MK, McCollester J, Binz S, Liew-Spilger A, Thomas S, Crepinsek A, Shariff F, Ploplis V, Castellino FJ. Targeted Thromboelastographic (TEG) Blood Component and Pharmacologic Hemostatic Therapy in Traumatic and Acquired Coagulopathy. Curr Drug Targets. 2016;17(8):954-70. PMID: 26960340

Agrahari G, Liang Z, Glinton K, Lee SW, Ploplis VA, Castellino FJ. Streptococcus pyogenes Employs Strain-dependent Mechanisms of C3b Inactivation to Inhibit Phagocytosis and Killing of Bacteria. J Biol Chem. 2016 Apr 22;291(17):9181-9. doi: 10.1074/jbc.M115.704221. Epub 2016 Mar 4. PMID: 26945067

Bao YJ, Liang Z, Mayfield JA, Lee SW, Ploplis VA, Castellino FJ. CovRS-Regulated Transcriptome Analysis of a Hypervirulent M23 Strain of Group A Streptococcus pyogenes Provides New Insights into Virulence Determinants. J Bacteriol. 2015 Oct;197(19):3191-205. doi: 10.1128/JB.00511-15. Epub 2015 Jul 27. PMID: 26216843

Chandrahas V, Glinton K, Liang Z, Donahue DL, Ploplis VA, Castellino FJ. Direct Host Plasminogen Binding to Bacterial Surface M-protein in Pattern D Strains of Streptococcus pyogenes Is Required for Activation by Its Natural Coinherited SK2b Protein. J Biol Chem. 2015 Jul 24;290(30):18833-42. doi: 10.1074/jbc.M115.655365. Epub 2015 Jun 12. PMID: 26070561

Gupta KK, Donahue DL, Sandoval-Cooper MJ, Castellino FJ, Ploplis VA. Abrogation of plasminogen activator inhibitor-1-vitronectin interaction ameliorates acute kidney injury in murine endotoxemia. PLoS One. 2015 Mar 23;10(3):e0120728. doi: 10.1371/journal.pone.0120728. eCollection 2015 Mar 23. PMID: 25799354

Bao Y, Liang Z, Booyjzsen C, Mayfield JA, Li Y, Lee SW, Ploplis VA, Song H, Castellino FJ. Unique genomic arrangements in an invasive serotype M23 strain of Streptococcus pyogenes identify genes that induce hypervirulence. J Bacteriol. 2014 Dec;196(23):4089-102. doi: 10.1128/JB.02131-14. Epub 2014 Sep 15. PMID: 25225265

Mayfield JA, Bao Y, Liang Z, Booyjzsen C, Li Y, Lee SW, Ploplis VA, Song H, Castellino FJ. Unique Genomic Arrangements in an Invasive Serotype M23 Strain of Streptococcus pyogenes Identify Genes that Induce Hypervirulence. J Bacteriol. 2014 Dec 1;196(23):4089-102. doi: 10.1128/JB.02131-14. Epub 2014 Sep 15. PMID: 25225265 [PubMed - in process]

Mayfield JA, Liang Z, Agrahari G, Lee SW, Donahue DL, Ploplis VA, Castellino FJ. Mutations in the control of virulence sensor gene from Streptococcus pyogenes after infection in mice lead to clonal bacterial variants with altered gene regulatory activity and virulence. PLoS One. 2014 Jun 26;9(6):e100698. doi: 10.1371/journal.pone.0100698. eCollection 2014. PMID:24968349

Bhattacharya S, Liang Z, Quek AJ, Ploplis VA, Law R, Castellino FJ. Dimerization Is Not a Determining Factor for Functional High Affinity Human Plasminogen Binding by the Group A Streptococcal Virulence Factor PAM and Is Mediated by Specific Residues within the PAM a1a2 Domain. J Biol Chem. 2014 Aug 1;289(31):21684-93. doi: 10.1074/jbc.M114.570218. Epub 2014 Jun 24. PMID:24962580

Genua M, D'Alessio S, Cibella J, Gandelli A, Sala E, Correale C, Spinelli A, Arena V, Malesci A, Rutella S, Ploplis VA, Vetrano S, Danese S. The urokinase plasminogen activator receptor (uPAR) controls macrophage phagocytosis in intestinal inflammation. Gut. 2014 May 21. pii: gutjnl-2013-305933. doi: 10.1136/gutjnl-2013-305933. [Epub ahead of print]. PMID:24848264

Ploplis VA, Donahue DL, Sandoval-Cooper MJ, MorenoCaffaro M, Sheets P, Thomas SG, Walsh M, Castellino FJ. Systemic Platelet Dysfunction Is the Result of Local Dysregulated Coagulation and Platelet Activation in the Brain in a Rat Model of Isolated Traumatic Brain Injury. J Neurotrauma. 2014 May 21. [Epub ahead of print]. PMID:24605991

Zhang Y, Mayfield JA, Ploplis VA, Castellino FJ. The β-domain of cluster 2b streptokinase is a major determinant for the regulation of its plasminogen activation activity by cellular plasminogen receptors. Biochem Biophys Res Commun. 2014 Feb 21;444(4):595-8. doi: 10.1016/j.bbrc.2014.01.109. Epub 2014 Jan 31. PMID:24486550

Castellino FJ, Chapman MP, Donahue DL, Thomas S, Moore SS, Wohlauer MV, Fritz B, Yount R, Ploplis V, Davis P, Evans E, Walsh M. Traumatic brain injury causes platelet adenosine diphosphate and arachidonic acid receptor inhibition independent of hemorrhagic shock in humans and rats. J Trauma Acute Care Surg. 2014 May;76(5):1169-1176. Doi:10.1097/TA.0000000000000216. PMID:24747445