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Stipan Jonjic

Name of the laboratory

CapRi: Center for monoclonal antibody production
Center for Proteomics
Faculty of Medicine
University of Rijeka
B. Branchetta 20, 51 000 Rijeka, Croatia
+385 51 651 260 / 651 250

Members of the laboratory

Members: Center for Proteomics
Team Leader
Stipan Jonjic stipan.jonjic@medri.uniri.hr
Research Personnel
Tihana Lenac Rovis tihana.lenac@medri.uniri.hr
Berislav Lisnic berislav.lisnic@medri.uniri.hr
Johanna Julia Reichel johanna.juliar@medri.uniri.hr
Vanda Juranic Lisnic vanda.juranic@medri.uniri.hr
PhD Students
Antonija Miletic antonija.miletic@medri.uniri.hr
Adriana Tomic adriana.damjanovic@medri.uniri.hr
Tihana Trsan tihana.trsan@medri.uniri.hr
Ilija Brizic ilija.brizic@medri.uniri.hr
Paola Kucan paola.kucan@medri.uniri.hr
Lea Hirsl lea.hirsl@medri.uniri.hr
Ana Lesac ana.lesac@medri.uniri.hr
Laboratory Engineers
Karmela Miklic karmela.miklic@medri.uniri.hr
Suzana Malic suzana.malic@medri.uniri.hr
Danica Rebic danica.rebic@medri.uniri.hr
Ante Mise lamri.mise@net.hr
Edvard Marinovic edimarinovic@gmail.com
Research administrative and management support
Ani Gerbin ani.gerbin@medri.uniri.hr
Josipa Zivkovic josipa.zivkovic@medri.uniri.hr
Iva Stosic iva.stosic@medri.uniri.hr

Laboratory activity

The Center for Proteomics, established in 2006 at the University of Rijeka Faculty of Medicine, is focused on high-throughput monoclonal antibodies (mAb) development for cutting-edge applications, including proteome analysis. It already disposes of a bank with several hundred hybridoma cell lines secreting mAbs to a large variety of target proteins. The Center has participated in more than thirty collaborative projects with prestigious research institutes, universities and biotech SMEs from SE Europe, EU and the USA.

These projects are mainly based on the production and characterization of mAbs for research purposes. In many instances the reagents generated at the Center have played a key role in various discoveries and resulted in joint publications in the leading journals.

Research activities

The Center's pilot project for the high-throughput production of mAbs was performed on the VZV (Varicella Zoster Virus) proteome. Ever since, the Center has been continuously working on new projects and services, which include:

  • generation of diverse sets of mAbs against murine and human cytomegalovirus (CMV) proteins (including mAbs against viral proteins expressed on the surface of infected cells (neutralising Ab capacity), structural and non-structural CMV proteins with an emphasis on viral proteins involved in immunoevasion functions and viral MHC I-like proteins for studies in structural biology);
  • generation of mAbs to other immunologically important targets (mAbs against viral chemokines and cytokines, mAbs to several proteins expressed on human NK cells, potential markers on pancreatic tumor, neuro-stem cells);
  • custom mAbs/hybridoma development;
  • development of novel immunotherapeutic approaches to treat viral infections based on fusion proteins consisting of anti-viral mAbs and soluble ligands for different lymphocyte receptors.

Techniques available

  • Protein immunogen expression and purification
  • Production of murine mAbs
  • mAb purification (HPLC, 5mg scale, adaptation to serum-free media)
  • mAb fragmentation
  • Ab characterization (western blot, immunoprecipitation, ELISA, flow cytometry, laser scanning, confocal microscopy, immunohistochemistry)
  • Mycoplasma testing

Publications (2019-present)

  • Arapović M, Brizić I, Popović B, Jurković S, Jordan S, Krmpotić A, Arapović A, Jonjić S: Intrinsic contribution of perforin to NK cell homeostasis during viral infection. Frontiers in Immunology, accepted for publication (2016)
  • Lenac Rovis T, Jonjic, S: Pregnancy-specific glycoprotein (PSG) expression in normal gastrointestinal tract and in tumours detected with novel monoclonal antibodies. mAbs, accepted for publication (2016)
  • Mndelboim O, Glasner A, Roth Z, Varvak A, Miletic A, Isaacson B, Bar-On Y, Jonjic S, Khalaila I: Identification of novel O glycosylations in the NK killer receptor Ncr1 essential for its activity, Cell Discovery, accepted for publication (2016) (IF: 12.413)
  • Glasner A, Simic H, Miklić K,Roth Z, Berhani O, Khalaila I, Jonjic S, Mandelboim O: Expression, Function, and Molecular Properties of the Killer Receptor Ncr1-Noé; Journal of Immunology, 195(8):3959-3969, 2015
  • Lisnic B, Juranic Lisnic V, Jonjic S: NK cell interplay with cytomegalovirusea, Current Opinion in Virology, 15:9–18, 2015 (IF: 6.064)
  • Verweij M, Wellish M, Whitmer T, Malouli D, Lapel M, Jonjic S, Haas J, DeFilippis V, Mahalingam R, Früh K: Varicella Viruses Inhibit Interferon- Stimulated JAK-STAT Signaling through Multiple Mechanisms, PLoS Pathogens, 11(5): e1004901., 2015 (IF: 7.562)
  • Bradford R, Yoo Y, Golemac M, Pugel E, Jonjic S, Britt WJ: Murine CMV-Induced Hearing Loss Is Associated with Inner Ear Inflammation and Loss of Spiral Ganglia Neurons, PLoS Pathogens 11(4): e1004774., 2015 (IF: 7.562)
  • Arapovic J, Arapovic M, Golemac M, Traven L, Tomac J, Rumora D, Razic E, Krmpotic A, Jonjic S: The specific NK cell response in concert with perforin prevents CD8+ T cell mediated immunopathology after mouse cytomegalovirus infection, Medical Microbiology and Immunology, 204(3):335-344, 2015 (IF: 3.038)
  • Yossef R, Gur C, Shemesh A, Guttman O, Hadad U, Nedvetzki S, Miletic A, Nalbandyan K, Cerwenka A, Jonjic S, Mandelboim O, Porgador A: Targeting Natural Killer Cell Reactivity by Employing Antibody to NKp46: Implications for Type 1 Diabetes. PlosOne, 10(2):e0118936, 2015 (IF: 3.234)
  • Gur C, Ibrahim Y, Isaacson B, Yamin R, Abed J, Gamliel M, Enk J, Bar-On Y, Stanietsky-Kaynan N, Coppenhagen-Glazer S, Shussman N, Almogy G, Cuapio A, Hofer E, Mevorach D, Tabib A, Ortenberg R, Markel G, Miklic K, Jonjic S, Brennan CA, Garrett WS, Bachrach G, Mandelboim O: Binding of the Fap2 Protein of Fusobacterium nucleatum to Human Inhibitory Receptor TIGIT Protects Tumors from Immune Cell Attack. Immunity, 42(2):344-55, 2015 (IF: 21.561)
  • Jonjic S: CMV Immunology. Cellular and Molecular Immunology, 12(2):125-7, 2015 (IF: 4.112)
  • Lemmermann N, Krmpotic A, Podlech J, Brizic I, Prager A, Adler H, Karbach A, Wu Y, Jonjic S, Reddehase MJ, Adler B: Non-redundant and redundant roles of cytomegalovirus gH/gL complexes in host organ entry and intra-tissue spread., PLoS Pathogens, 11(2):e1004640, 2015 (IF: 7.562)
  • Eifler M, Uecker R, Weisbach H, Bogdanow B, Richter E, König L, Vetter B, Lenac-Rovis T, Jonjic S, Neitzel H, Hagemeier C, Wiebusch L: PUL21a-Cyclin A2 Interaction is Required to Protect Human Cytomegalovirus-Infected Cells from the Deleterious Consequences of Mitotic Entry. PLoS Pathogens, 13;10(10):e1004514; 2014 (IF: 7.562)
  • Pyzik M, Dumaine AA, Charbonneau B, Fodil-Cornu N, Jonjic S, Vidal SM: Viral MHC Class I-like Molecule Allows Evasion of NK Cell Effector Responses In Vivo. Journal of Immunology, 193(12):6061-9, 2014 (IF: 4.922)
  • Gabaev I, Elbasani E, Ameres S, Steinbrück L, Stanton R, Döring M, Lenac Rovis T, Kalinke U, Jonjic S, Moosmann A, Messerle M:Expression of the Human Cytomegalovirus UL11 Glycoprotein in Viral Infection and Evaluation of its Effect on Virus-Specific CD8 T Cells., Journal of Virology, 88(24):14326, 2014 (IF: 4.439)
  • Brizic I, Lenac Rovis T, Krmpotic A, Jonjic S: MCMV avoidance of recognition and control by NK cells. Seminars in Immunopathology, 36(6):641-50, 2014 (IF: 7.748)
  • Celis-Gutierrez J, Boyron M, Walzer T, Pandolfi PP, Jonjic S, Olive D, Dalod M, Vivier E, Nunès JA: Dok1 and Dok2 proteins regulate natural killer cell development and function. EMBO Journal, 33(17):1928-40, 2014 (IF: 10.434)
  • Baird NL, Bowlin JL, Yu X, Jonjic S, Haas J, Cohrs RJ, Gilden D: Varicella zoster virus DNA does not accumulate in infected human neurons.Virology, 458-459:1-3, 2014 (IF: 3.321)
  • Crouse J, Bedenikovic G, Wiesel M, Ibberson M, Xenarios I, Von Laer D, Kalinke U, Vivier E, Jonjic S, Oxenius A: Type I Interferons Protect T Cells against NK Cell Attack Mediated by the Activating Receptor NCR1. Immunity, 40(6):961-73, 2014 (IF: 21.561)
  • Slavuljica I, Kvestak D, Huszthy P, Kosmac K, Britt W, Jonjic S: Immunobiology of Congenital Cytomegalovirus Infection of the Central Nervous System - Murine Cytomegalovirus Model. Cellular and Mollecular Immunology, 12(2):180-91, 2014 (IF: 4.112)
  • Zarama A, Perez-Carmona N, Farre´ D, Tomic A, Borst EM, Messerle M, Jonjic S, Engel P, Angulo A: Cytomegalovirus m154 hinders CD48 cell-surface expression and promotes viral escape from host natural killer cell control. PLoS Pathogens, 10(3):e1004000; 2014 (IF: 7.562)
  • Trilling M, Khanh Le V, Rashidi-Alavijeh J, Katschinski B, Scheller J, Rose-John S, Androsiac G, Jonjic S, Poli V, Pfeffer K, Hengel H: 'Activated' STAT proteins - a paradoxical consequence of inhibited JAK-STAT signalling in cytomegalovirus-infected cells. Journal of Immunology, 192(1):447-58; 2014 (IF: 4.922)
  • Geyer H, Hartung E, Mages HW, Weise C, Beluzic R, Vugrek O, Jonjic S, Kroczek RA, Voigt S: Cytomegalovirus expresses the chemokine homologue vXCL1 capable of attracting XCR1+CD4- dendritic cells. Journal of Virology, 88(1):292-302; 2014 (IF: 4.439)
  • Trsan T, Busche A, Abram M, Wensveen FM, Lemmermann NA, Arapovic M, Babic M,Tomic A, Golemac M, Brinkmann MM, Jäger W, Oxenius A, Polic B, Krmpotic A, Messerle M, Jonjic S: Superior induction and maintenance of protective CD8 T cells in mice infected with MCMV vector expressing RAE-1γ. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 110(41):16550-5, 2013
  • Juranic Lisnic V, Babic Cac M, Lisnic B, Trsan T, Mefferd A, Mukhopadhyay CD, Cook CH, Jonjic S, Trgovcich J: Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface. PLoS Pathogens, 9(9), 2013
  • Wensveen MF, Lenartic M, Jelencic V,  Lemmermann AN,  ten Brinke A, Jonjic S, Polic B: NKG2D Induces Mcl-1 Expression and Mediates Survival of CD8 Memory T Cell Precursors via Phosphatidylinositol 3-Kinase. Journal of Immunology, 191(3):1307-15, 2013
  • Jordan S, Ruzsics Z, Mitrovic M, Baranek T, Arapovic J, Krmpotic A, Vivier E, Dalod M, Jonjic S, Döelken L, Koszinowski UH: Natural killer cells are required for extramedullary hematopoiesis following murine cytomegalovirus infection. Cell Host & Microbe, 13, 535-545; 2013
  • Stanietsky N, Lenac T, Glasner A, Seidel E, Tsukerman P, Yamin R, Enk J, Jonjic S, Mandelboim O: Mouse TIGIT inhibits NK-cell cytotoxicity upon interaction with PVR. European Journal of Immunology, 43(8):2138-50, 2013
  • Lenac Rovis T, Bailer SM, Pothineni VR, Ouwendijk WJ, Simic H, Babic M, Miklic K, Malic S, Verweij MC, Baiker A, Gonzalez O, von Brunn A, Zimmer R, Früh K,Verjans GM, Jonjic S, Haas J.: A comprehensive analysis of varicella zoster virus proteins using a new monoclonal antibody collection. Journal of Virology, 87(12):6943-54, 2013.
  • Miletić A, Krmpotić A, Jonjić S: The evolutionary arms race between NK cells and viruses: Who gets the short end of the stick? European Journal of Immunology, 43(4):867-77; 2013
  • Lankry D, Lenac Rovis T, Jonjic S, Mandelboim O: The interaction between CD300a and Phosphatidylserine inhibits tumor cell killing by NK cell. European Journal of Immunology; 43(8):2151-61, 2013
  • Kosmac K, Bantug R, Pugel E, Cekinovic Dj, Jonjic S, Britt W: Glucocorticoid Treatment of MCMV Infected Newborn Mice Attenuates CNS Inflammation and Limits Deficits in Cerebellar Development (PPATHOGENS-D-12-02090R1) PLoS Pathogens 9(3): e1003200. doi:10.1371/journal.ppat.1003200; 2013
  • Handke W, Luig C, Popovic B, Krmpotic A, Jonjic S, Brune W: Viral inhibition of BAK promotes murine cytomegalovirus dissemination to salivary glands. Journal of Virology 87(6):3592-6; 2013
  • Wensveen FM, Klarenbeek PL, van Gisbergen K, Pascutti MF, Derks I, van Schaik B, ten Brinke A, de Vries N, Cekinovic D, Jonjic S, van Lier R, Eldering E: Pro-Apoptotic Protein Noxa Regulates Memory T Cell Population Size and Protects against Lethal Immunopathology. Journal of Immunology 190(3):1180-91; 2013
  • Yu X, Seitz S, Pointon T, Bowlin J, Cohrs R, Jonjić S, Haas J, Wellish M, Gilden D: Varicella Zoster Virus Infection of Highly Pure Terminally Differentiated Human Neurons. Journal of Neurovirology 19(1):75-81; 2013
  • Borst M, Kleine-Albers J, Gabaev I, Babic M, Wagner K, Binz A, Degenhardt I, Kalesse M,Jonjic S, Bauerfeind R, Messerle M: The human cytomegalovirus UL51 protein is essential for viral genome cleavage-packaging and interacts with the terminase subunits pUL56 and pUL89. Journal of Virology 87(3):1720-32; 2012
  • Mitrovic M, Arapovic J, Traven L, Krmpotic A, Jonjić S: Innate immunity regulates adaptive immune response: lessons learned from studying the interplay between NK and CD8(+) T cells during MCMV infection. Medical Microbiology and Immunology 201(4):487-95; 2012
  • Rodrıguez-Martin S, Kropp K, Wilhelmi V, Juranic Lisnic V,Yuan Hsieh W, Blanc M, Livingston A, Busche A, Tekotte H, Messerle M, Auer M, Fraser I, Jonjic S, Angulo A, Reddehase M, Ghazal P: Ablation of the Regulatory IE1 Protein of Murine Cytomegalovirus Alters In Vivo Pro-inflammatory TNFalpha Production during Acute Infection. PLoS Pathogens 8(8): e1002901. doi:10.1371/journal.ppat.1002901; 2012
  • van Gisbergen K, Kragten N, Hertoghs K , Wensveen F, Jonjic S, Hamann J, Nolte M, van Lier R: Mouse Hobit is a homolog of the transcriptional repressor Blimp-1 that regulates NKT cell effector differentiation. Nature Immunology 13(9):864-71; 2012
  • Mandaric S, Walton S, Ruelicke T, Richter K, Girard-Madoux M, Clausen B, Zurunic A, Kamanaka M, Flavell R, Jonjic S, Oxenius A: IL-10 Suppression of NK/DC Crosstalk Leads to Poor Priming of MCMV-Specific CD4 T Cells and Prolonged MCMV Persistence. PLoS Pathogens 8(8): e1002846. doi:10.1371/journal.ppat.1002846; 2012
  • Glasner A, Zurunic A, Meningher T, Lenac Rovis T, Tsukerman P, Bar-On Y, Yamin R, Meyers A, Mandeboim M, Jonjic S, Mandelboim O: Elucidating the mechanisms of influenza virus recognition by Ncr1. PLoS ONE 7(5):e36837; 2012
  • Poglitsch, M, Weichhart T, Hecking M, Werzowa J, Katholnig K, Antlanger M, Krmpotic A, Jonjic S, Hörl W, Zlabinger G, Puchhammer E, Säemann M: CMV Late Phase-Induced mTOR Activation Is Essential for Efficient Virus Replication in Polarized Human Macrophages. American Journal of Transplantation 2(6):1458-68. doi: 10.1111/j.1600-6143.2012.04002.x; 2012
  • Mitrovic M, Arapovic J, Jordan S, Fodil-Cornu N, Ebert S, Vidal SM, Krmpotic A, Reddehase MJ, Jonjic S: The NK-cell response to mouse cytomegalovirus infection affects the level and kinetics of the early CD8+ T-cell response. Journal of Virology 86(4):2165-75; 2012
  • Marcinowski L, Tanguy M, Krmpotic A, Rädle B, Juranic Lisnic V, Tuddenham L, Chane-Woon-Ming B, Ruzsics Z, Erhard F, Benkartek C, Babic M, Zimmer R, Trgovcich J, Koszinowski U, Jonjic S, Pfeffer S, Dölken L: Degradation of cellular miR-27 by a novel, highly abundant viral transcript is important for efficient virus replication in vivo. PLOS Pathogens, 8(2): e1002510. doi:10.1371/journal.ppat.1002510, 2012
  • Slavuljica I, Krmpotić A, Jonjić S: Manipulation of NKG2D ligands by cytomegaloviruses: impact on innate and adaptive immune response. Frontiers in Immunology 2:85. doi: 10.3389/fimmu. 2011.00085; 2011
  • Jordan S, Krause J, Prager A, Mitrovic M, Jonjic S, Koszinowski UH, Adler B: Virus Progeny of MCMV Bacterial Artificial Chromosome pSM3fr Shows Reduced Growth in Salivary Glands Due to a Fixed Mutation of MCK-2. Journal of Virology 85(19):10346-53; 2011
  • Babic M, Krmpotic A, Jonjic S: All is fair in virus-host interactions: NK cells and cytomegalovirus. Trends in Molecular Medicine 17(11):1471-4941; 2011
  • Pyzik M, Charbonneau B, Gendron-Pontbriand EM, Babic M, Krmpotic A, Jonjic S, Vidal S:Distinct MHC class I-dependent NK cell-activating receptors control cytomegalovirus infection in different mouse strains. Journal of Experimental Medicine 208(5):1105-17; 2011
  • Jovanovic I, Radosavljevic G, Mitrovic M, Lisnic Juranic V, McKenzie A, Arsenijevic N, Jonjic S, Lukic M: ST2 Deletion Enhances Innate and Acquired Immunity to Murine Mammary Carcinoma. European Journal of Immunology 41:7,1902-1912; 2011.
  • Radosavljevic G, Jovanovic I, Majstorovic I, Mitrovic M, Lisnic VJ, Arsenijevic N, Jonjic S, Lukic ML: Deletion of galectin-3 in the host attenuates metastasis of murine melanoma by modulating tumor adhesion and NK cell activity. Clinical and Experimental Metastasis28(5):451-62; 2011
  • Slavuljica I, Busche A, Babic M, Mitrovic M, Gasparović I, Cekinovic Dj, Markova Car E, Pernjak Pugel E, Cikovic A, Juranic Lisnic V, Britt WJ, Koszinowski U, Messerle M, Krmpotic A, Jonjic S: Recombinant mouse cytomegalovirus expressing a ligand for the NKG2D receptor is attenuated and has improved vaccine properties. Journal of Clinical Investigation 120(12):4532-45; 2010
  • Babic M, Pyzik M, Zafirova B, Mitrovic M, Butorac V, Lanier LL, Krmpotic A, Vidal SM andJonjić S: Cytomegalovirus immunoevasin reveals the physiological role of „missing self” recognition in NK cell dependent virus control in vivo. Journal of Experimental Medicine207(12):2663-2673; 2010
  • Doelken L, Krmpotic A, Koethe S, Tuddenham L, Tanguy M, Marcinowska L, Ruzsics Z, Elefant N, Altuvia Y, Margalit H, Koszinowski U, Jonjic S, Pfeffer S: Cytomegalovirus microRNAs facilitate persistant virus infection in salivary glands. PloS Pathogens14;6(10):e1001150; 2010
  • Lankry D, Simic H, Klieger Y, Levi-Schaffer F, Jonjic S, Mandelboim O: Expression and function of CD300 in NK cells. Journal of Immunology 185(5):2877-86; 2010
  • Champsaur M, Beilke JN, Ogasawara K, Koszinowski UH, Jonjic S, Lanier LL: Intact NKG2D-Independent Function of NK Cells Chronically Stimulated with the NKG2D Ligand Rae-1. Journal of Immunology 185(1):157-65; 2010
  • Juranic Lisnic V, Krmpotic A, Jonjic S: Modulation of natural killer cell activity by viruses.Current Opinion in Microbiology 13:1-10; 2010
  • Stanietsky N, Simic H, Arapovic J, Toporik A, Levy O, Novik A, Levine Z, Beiman M, Dassa L, Achdout H, Stern-Ginossar N, Tsukerman P, Jonjic S, Mandelboim O: The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. Proceedings of the National Academy of Sciences of the United States of America 106(42):17858-63; 2009
  • Arapovic J, Lenac T, Antulov R, Polic B, Ruzsics Z, Carayannopoulos LN, Koszinowski UH, Krmpotic A, Jonjic S.: Differential susceptibility of RAE-1 isoforms to mouse cytomegalovirus. Journal of Virology 83(16):8198-207; 2009
  • Zafirova B, Mandaric S, Antulov R, Krmpotic A, Jonsson H, Yokoyama WM, Jonjic S, Polic B: Altered NK cell development and enhanced NK cell-mediated resistance to mouse cytomegalovirus in NKG2D-deficient mice. Immunity 31(2):270-82; 2009
  • Arapovic J, Lenac Rovic T, Reddy AB, Krmpotic A, Jonjic S: Promiscuity of MCMV immunoevasin of NKG2D: m138/fcr-1 down-modulates RAE-1epsilon in addition to MULT-1 and H60. Molecular Immunology 47(1):114-22; 2009
  • Kielczewska A, Pyzik M, Sun T, Krmpotic A, Lodoen M B, Munks M W, Babic M, Hill A B, Koszinowski U H, Jonjić S, Lanier L, Vidal S: Ly49P recognition of cytomegalovirus-infected cells expressing H2-Dk and CMV-encoded m04 correlates with the NK cell antiviral response. Journal of Experimental Medicine 206(3):515-23; 2009
  • Cekinovic D, Golemac M, Pugel EP, Tomac J, Cicin-Sain L, Slavuljica I, Bradford R, Misch S, Winkler TH, Mach M, Britt WJ, Jonjic S. Passive immunization reduces MCMV induced brain pathology in newborn mice. Journal of Virology 82(24):12172-80; 2008
  • Bantug G, Cekinovic D, Bradford R, Koontz T, Jonjic S, Britt W J: CD8+ T-lymphocytes control MCMV replication in the central nervous system of newborn animals. Journal of Immunology 181(3):2111-23; 2008
  • Koontz T, Bralic M, Tomac J, Pernjak-Pugel E, Bantug G, Jonjic S, and Britt W J: Altered Development of the Brain after Focal Herpesvirus Infection of the CNS. Journal of Experimental Medicine 205(2):423-35; 2008