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Candidate's Name , Ph.D.Senior Research InvestigatorPhiladelphia, PA, USATel.: PHONE NUMBER AVAILABLE (cell)E-mail: EMAIL AVAILABLECitizenship: US CitizenAREAS OF INTEREST AND EXPERIENCE: Molecular and cell biology. Biochemistry. Cancer research. Heparin-induced thrombocytopenia/thrombosis. Hematological disorders. Cell surface receptors and nuclear receptors. Cell nucleus structure and functions. Small molecule screening. Control of protein expression. Serine proteases. G Protein-Coupled Receptors (GPCR) & signal transduction. Immunology. Plant cloning and propagation.Skills: RNA/DNA purification, handling, and manipulations. Plasmid design for RNA & protein expression in heterologous systems. PCR, RT-PCR. Northern and Southern blotting. Protein expression and purification from insect, mammalian and bacterial cells. Western blotting. Cell-based assays. ELISA. Luciferase assays. Immuno cytochemistry. Immunoprecipitation. Affinity-, ion-exchange-, SE-, and thin layer chromatography. Light microscopy. Phase and fluorescent microscopy imaging. Micro injections. DLS. Adeno viruses. Deuterium exchange MS data analysis. Radioactive materials handling.EMPLOYMENT:.April 2022 to current: Senior Research Investigator. Ecuagenera. Laboratorio de Ecuagenera, Gualaceo, Ecuador (first on site in Gualaceo, Ecuador, and currently online from Philadelphia, PA.)Duties: Consulting on various aspects of species-specific micropropagation and cloning of orchids and other higher plants. Conducting research and analysis of the scientific data and methodology pertinent to plant cloning and micropropagation, choosing the methods of micropropagation for different species, teaching staff the scientific concepts beyond routine bench work.November 2001 to March 2022: Senior Research Investigator. University of Pennsylvania. Department of Pathology and Laboratory Medicine, Perelman Medical School, Philadelphia, PA.Duties: Choosing the strategy and methods for investigation, conducting research and analysis of the scientific data and methodology pertinent to the projects, designing and performing bench work, compiling and analyzing the results obtained, preparing data for publication, collaborating with colleagues and supervisors of other groups around the world. Serving as a radiation safety laboratory officer. Major Project: Heparin-induced thrombocytopenia/thrombosis. January 2001 to August 2001: Senior Scientist. Serono Corporation. Molecular Biosciences Dept., Serono Reproductive Biology Institute, Randolph, MA. Duties: Initial drug development. Performing bench work, conducting research and analysis of the scientific data and methodology pertinent to the projects, compiling and analyzing the results obtained, preparing reports for internal use. Project: EGFR- and Src-mediated activation of MEK/ERK MAP kinases. G Protein- Coupled Receptor (GPCR)-based research.2November 1997 to January 2001: Research Associate. Worcester Foundation for Biomedical Research/University of Massachusetts Medical School. Worcester, MA. Duties: Conducting research and analysis of the scientific data and methodology pertinent to the projects, choosing methods for investigation, designing and performing bench work, compiling and analyzing the results obtained, preparing data for publication.Projects: Intranuclear traffic and nucleolar functions of SRP proteins and RNase P RNA. Created a novel system for inducible expression of RNA Pol I and RNA Pol III products in mammalian cells. The system developed represented a new essential tool for the small RNAs studies.March 1996 to November 1997: Postdoctoral Researcher. Sidney Kimmel Cancer Center. San Diego, CA.Project: Selective activation of an apoptotic retinoid precursor in macrophage cell lines. Discovered the mechanism of the selective activation. August 1994 to March 1996: Postdoctoral Researcher. Hopital de la Pitie-Salpetriere. Laboratoire du Service d'Oncologie Medicale, Paris, France. Project: Cancer gene therapy. Design of new constructs for gene therapy. Cell transfection with exogenous RNA and DNA encoding the herpes simplex virus thymidine kinase (HSV-tk) to sensitize the cells to ganciclovir (GCV). EDUCATION:1989-1993: Ph.D. in Chemistry (Biochemistry and Molecular Biology). Russian Academy of Science. Shemyakin and Ovchinnikov Institute of Bio-Organic Chemistry, Moscow, Russia. GPA 4.00. Thesis Title: "The cDNA Sequences Encoding the Granzyme-Like Proteinases of Rat Duodenum." Discovered a novel rat intestinal proteinase with dual trypsin- and chymotrypsin-like specificities. Purified RNA and DNA from different cells and tissues, developed cDNA libraries, performed Northern and Southern blottings, PCRs, cloning, etc. Characterized cDNA sequences encoding the granzyme-like rat intestinal proteinases and a human homologue of eubacterial ATP-dependent Lon protease. 1982-1989: Master of Science in Biochemistry, with Honor. Donetsk National University. Donetsk, Ukraine. GPA 3.88.Additional courses, seminars, and workshops in Biological Sciences: 1999: Analytical & Quantitative Light Microscopy Course. MBL, Woods Hole, MA. FUNDING HISTORY AND AWARDS:2003-2005: Principal Investigator. American Heart Association. Grant 0365549U,$100,000.00.May 12, 2004: American Stroke Association/American Heart Association Award for Outstanding Effort in the Area of Research and Education in the Fight against Heart Disease and Stroke.TEACHING EXPERIENCE:November 2001 to March 2022: Senior Research Investigator. University of Pennsylvania. Department of Pathology and Laboratory Medicine, R. and R. Perelman Medical School, Philadelphia, PA. Teaching students and lab newcomers on various Molecular and Cell Biology/ Biochemistry techniques used in the lab. 1989. Donetsk National University. Donetsk, Ukraine. Teaching chemistry and biology to the technical college students.3RESEARCH PUBLICATIONS:Cai Z, Bdeir, K, Yarovoi SV, Rauova L, Arepally G, Khandelwal S, Rollin J, Gruel Y, Zaitsev S, Poncz M, Greene MI, and Cines DB. Modulation of ultralarge immune complexes in heparin-induced thrombocytopenia. Journal of Thrombosis and Haemostasis. 2023. 2023 Mar;21(3):652-666. PMID: 36696211, DOI: 10.1016/j.jtha.2022.11.043Khandelwal S, Barnes A, Rauova L, Sarkar A, Rux AH, Yarovoi SV, Zaitsev S, Lambris JD, Myoung SS, Johnson A, Lee GM, Duarte M, Poncz M, Arepally GM, Cines DB. Complement mediates binding and procoagulant effects of ultra-large HIT immune complexes. Blood. 2021; 138(21):2106-16. PMID: 34189574, DOI: 10.1182/blood.PHONE NUMBER AVAILABLEArmstead WM, Hekierski H, Pastor P, Yarovoi S, Higazi AA, Cines DB. Release of IL-6 After Stroke Contributes to Impaired Cerebral Autoregulation and Hippocampal Neuronal Necrosis Through NMDA Receptor Activation and Upregulation of ET- 1 and JNK. Transl Stroke Res. 2019 Feb;10(1):104-111. PMID: 29476447, DOI: 10.1007/sPHONE NUMBER AVAILABLE-zFlorova G, Azghani AO, Karandashova S, Schaefer C, Yarovoi SV, Declerck PJ, Cines DB, Idell S, Komissarov AA. Targeting plasminogen activator inhibitor-1 in tetracycline-induced pleural injury in rabbits. Am J Physiol Lung Cell Mol Physiol. 2018 Jan 1;314(1):L54-L68. PMID: 28860148, DOI: 10.1152/ajplung.00579.2016Armstead WM, Hekierski H, Yarovoi S, Higazi AA, Cines DB. tPA variant tPA-A 296- 299Prevents Impairment of cerebral autoregulation and necrosis of hippocampal neurons after stroke by inhibiting upregulation of ET-1. J Neurosci Res. 2018 Jan;96(1):128-137. PMID: 28703856, DOI: 10.1002/jnr.24112 Cines DB, Yarovoi SV, Zaitsev SV, Lebedeva T, Rauova L, Poncz M, Arepally GM, Khandelwal S, Stepanova V, Rux AH, Cuker A, Guo C, Ocariza LM, Travers RJ, Smith SA, Kim H, Morrissey JH, Conway EM. Polyphosphate/platelet factor 4 complexes can mediate heparin-independent platelet activation in heparin-induced thrombocytopenia. Blood Adv. 2016 Nov 22;1(1):62-74. PMID: 29296696, DOI: 10.1182/bloodadvances.2016000877Armstead WM, Riley J, Yarovoi S, Higazi AA, Cines DB. Tissue-Type Plasminogen Activator-A296-299 Prevents Impairment of Cerebral Autoregulation After Stroke Through Lipoprotein-Related Receptor-Dependent Increase in cAMP and p38. Stroke. 2016 Aug;47(8):2096-102. PMID: 27354223, DOI: 10.1161/STROKEAHA.116.012678Cai Z, Yarovoi SV, Zhu Z, Rauova L, Hayes V, Lebedeva T, Liu Q, Poncz M, Arepally G, Cines DB, and Greene MI. Atomic description of the immune complex involved in heparin-induced thrombocytopenia. Nature Commun. 2015 Sep 22;6:8277. PMID: 26391892, DOI: 10.1038/ncomms9277 Hijazi, N, Abu Fanne, R, Abramovich, R, Yarovoi, S, Higazi, M, Abdeen, S, Basheer,M, Maraga, E, B Cines DB, and Higazi, AA. Endogenous plasminogen activators mediate progressive intracranial hemorrhage after traumatic brain injury in mice. Blood. 2015; 125(16):2558-67. PMID: 25673638, DOI: 10.1182/blood-PHONE NUMBER AVAILABLE4Litvinov, RI, Yarovoi, SV, Rauova, L, Barsegov, V, Sachais, BS, Rux, AH, Arepally, GM, Cines, DB, and Weisel JW. Distinct Specificity and Single-molecule Kinetics Characterize the Interaction of Pathogenic and Non-Pathogenic Antibodies Against Platelet Factor 4-Heparin Complexes with Platelet Factor 4. J. Biol. Chem. 2013; 288(46):33060-70. PMID: 24097975, DOI: 10.1074/jbc.M113.481598Armstead WM, Bohman LE, Riley J, Yarovoi S, Higazi AA, Cines DB. tPA-S(481)A Prevents Impairment of Cerebrovascular Autoregulation by Endogenous tPA after Traumatic Brain Injury by Upregulating p38 MAPK and Inhibiting ET-1. J. Neurotrauma. 2013; 30(22):1898-907. PMID: 23731391, DOI: 10.1089/neu.2013.2962Cuker A, Rux AH, Hinds JL, Dela Cruz M, Yarovoi SV, Brown IA, Yang W, Konkle BA, Arepally GM, Watson SP, Cines DB, Sachais BS. Novel diagnostic assays for heparin-induced thrombocytopenia. Blood. 2013; 121(18):3727-32. PMID: 23446735, DOI: 10.1182/blood-2XXX-XX-XXXX76Sachais BS, Litvinov RI, Yarovoi SV, Rauova L, Hinds JL, Rux AH, Arepally GM, Poncz M, Cuker A, Weisel JW, Cines DB. Dynamic antibody binding properties in the pathogenesis of HIT. Blood. 2012; 120(5):1137-42. PMID: 22577175, DOI: 10.1182/blood-PHONE NUMBER AVAILABLESachais BS, Rux AH, Cines DB, Yarovoi SV, Garner LI, Watson SP, Hinds JL, Rux JJ. Rational design and characterization of platelet factor 4 antagonists for the study of heparin-induced thrombocytopenia. (Plenary Paper) Blood. 2012; 119(25):5955-62. PMID: 22452981, DOI: 10.1182/blood-PHONE NUMBER AVAILABLE Armstead WM, Riley J, Yarovoi S, Cines DB, Smith DH, Higazi AA. tPA-S481A Prevents Neurotoxicity of Endogenous tPA in Traumatic Brain Injury. J.Neuro- trauma. 2012 Jun 10; 29(9):1794-802. PMID: 22435890, DOI: 10.1089/neu.2012.2328Kapustin A, Stepanova V, Aniol N, Cines DB, Poliakov A, Yarovoi S, Lebedeva T, Wait R, Ryzhakov G, Parfyonova Y, Gursky Y, Yanagisawa H, Minashkin M, Beabealashvilli R, Vorotnikov A, Bobik A, Tkachuk V. Fibulin-5 binds urokinase type plasminogen activator and mediates urokinase-stimulated 1- integrin-dependent cell migration. Biochem. J. 2012; 443(2):491-503. PMID: 22280367, DOI: 10.1042/BJ20110348Nassar T, Yarovoi S, Abu Fanne R, Waked O, Allen TC, Idell S, Cines DB, Higazi AA. Urokinase plasminogen activator regulates pulmonary arterial contractivity in mice. Am. J. Respir. Cell. Mol. Biol. 2011; 45(5):1015-21. PMID: 21617202, DOI: 10.1165/rcmb.2010-0302OCNassar, T, Bdeir, K, Yarovoi, S, Abu Fanne, R, Murciano, J-C, Idell, S, Allen, TC, Cines, DB, Higazi, AA. tPA regulates pulmonary vascular activity through NMDA receptors. Am. J. Physiol. Lung Cell. Mol. Physiol. 2011; 301(3):L307-14. PMID: 21571905, DOI: 10.1152/ajplung.00429.2010Nassar, T, Yarovoi, S, Abu Fanne, R, Akkawi, S, Jamal, M, Allen, TC, Idell, S, Cines, DB, and Higazi, AA-R. Regulation of Airway Contractility by Plasminogen Activators through N-Methyl-D-Aspartate Receptor-1. Am. J. Respir. Cell Mol. Biol. 2010; 43(6):703-11. PMID: 20097831, DOI: 10.1165/rcmb.2009-0257OC 5Abu Fanne, R, Nassar, T, Yarovoi, S, Rayan, A, Lamensdorf, I, Karakoveski, M, Polianski, V, Jamal, M, Cines DB, and Higazi, AA-R. Blood-brain barrier permeability and tPA-mediated neurotoxicity. Neuropharmacology. 2010; 58(7):972-80. PMID: 20060006, DOI: 10.1016/j.neuropharm.2009.12.017 Stepanova, V, Lebedeva, T, Kuo, A, Yarovoi, S, Tkachuk S, Zaitsev, S, Bdeir, K, Dumler, I, Marks, MS, Parfyonova, Y, Tkachuk, VA, Higazi, AA, Cines, DB. Nuclear Translocation of Urokinase-Type Plasminogen Activator. Blood, 2008, 112(1): 100-110. PMID: 18337556, DOI: 10.1182/blood-2007-07-104455 Wang, XQ, Bdeir, K, Yarovoi, S, Cines, DB, Fang, W, Abraham, E. Involvement of the urokinase kringle domain in lipopolysaccharide-induced acute lung injury. J.Immunol, 2006, 177 (8): 5550-5557. PMID: 17015742, DOI: 10.4049/jimmunol.177.8.5550Tarui, T, Akakura, N, Majumdar, M, Andronicos, N, Takagi, J, Mazar, AP, Bdeir, K, Kuo, A, Yarovoi, SV, Cines, DB, and Takada, Y. Direct interaction of the kringle domain of urokinase-type plasminogen activator (uPA) and integrin alpha v beta 3 induces signal transduction and enhances plasminogen activation. Thrombosis and Haemostasis, 2006, 95(3): 524-534. PMID: 16525582, DOI: 10.1160/TH05-06-0457Yarovoi, SV and Pederson, T. Human cell lines expressing hormone regulated T7 RNA polymerase localized at distinct intranuclear sites. Gene, 2001, 275 (1): 73-81. PMID: 11574154, DOI: 10.1016/s0378-1119(01)00652-7 Politz, JC*, Yarovoi, S*, Kilroy, SM, Gowda, K, Zwieb, C, and Pederson, T. Signal recognition particle components in the nucleolus. Proc. Natl. Acad. Sci. USA, 2000, 97: 55-60. (* J.C.P. and S. Y. contributed equally to this work.) PMID: 10618370, DOI: 10.1073/pnas.97.1.55Yarovoi, SV, Lu, X-P, Picard, N, Rungta, D, Rideout, D, and Pfahl, M. Selective activation of an apoptotic retinoid precursor in macrophage cell lines. J. Biol. Chem., 1998, 273: 20852-20859. PMID: 9694831, DOI: 10.1074/jbc.273.33.20852Yarovoi, SV, Mouawad, R, Colbere-Garapin, F, Soubrane, C, Khayat, D, and Rixe, O. In vitro sensitization of the B16 murine melanoma cells to ganciclovir by different RNA and plasmid DNA constructions encoding HSV-tk. Gene Therapy, 1996, 3: 913-918. PMID: 8908505, DOI: N/AGhoumari, AM, Rixe, O, Yarovoi, SV, Zerrouqi, A, Mouawad, R, Poynard, T, Opolon, P, Khayat, D, and Soubrane, C. Gene transfer in hepatocarcinoma cell lines: in vitro optimization of a virus-free system. Gene Therapy, 1996, 3: 483-490. PMID: 8789797, DOI: N/AZerrouqi, A, Rixe, O, Ghoumari, AM, Yarovoi, SV, Mouawad, R, Khayat, D, and Soubrane, C. Liposomal delivery of the herpes simplex virus thymidine kinase gene in glioma: improvement of cell sensitization to ganciclovir. Cancer Gene Therapy, 1996, 3: 385-392. PMID: 8988841, DOI: N/A Grigorenko, VG, Yarovoi, SV, Paulauskaite, R, and Amerik, AYu. Cloning of a cDNA for a granzyme-like protein III, a serine proteinase from rat duodenum. FEBS Letters, 1994, 342: 278-280. PMID: 8150084, DOI: PHONE NUMBER AVAILABLE- 5793(94)80516-46Amerik, AYu, Petukhova, GV, Grigorenko, VG, Lykov, IP, Yarovoi, SV, Lipkin, VM, and Gorbalenya, AE. Cloning and sequence analysis of cDNA for a human homologue of eubacterial ATP-dependent Lon proteases. FEBS Letters, 1994, 340: 25-28. PMID: 8119403, DOI: PHONE NUMBER AVAILABLE(94)80166-5 Amerik, A Yu, Yarovoi, SV, Grigorenko, VG, and Antonov, VK. Identification, sequence analysis, and characterization of cDNA clones encoding two granzyme- like serine proteinases from rat duodenum. FEBS Letters, 1993, 324: 226-230. PMID: 8508925, DOI: PHONE NUMBER AVAILABLE(93)81398-j