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Vladka Čurin Šerbec

Name of the laboratory

Center for the Production of Diagnostic Reagents and for Research and research group Biomedicine
Blood Trasfusion Centre of Slovenia
Šlajmerjeva 6, 1000 Ljubljana, Slovenia
+ 386 1 5438 100

Members of the laboratory

Members: Center for the Production of Diagnostic Reagents and for Research
Head
Vladka Čurin Šerbec vladka.curin@ztm.si
Research Personnel
Maja Černilec maja.cernilec@ztm.si
Katrina Hartman katrina.hartman@ztm.si
Valerija Hladnik valerija.hladnik@ztm.si
Uroš Rajčević uros.rajcevic@ztm.si
PhD Students
Sandra Omejec sandra.omejec@ztm.si
Laboratory Engineers
Boštjan Smrekar bostjan.smrekar@ztm.si
Melita Gracar melita.gracar@ztm.si
Technicians
Marjana Šprohar marjana.sprohar@ztm.si

Laboratory activity

Center for the Production of Diagnostic Reagents and for Research (CPDRR) was established two decades ago. One of its main activities was the production of diagnostic reagents for blood grouping under GMP, based on mouse monoclonal antibodies, which were developed, validated, registered (and later licensed) by CPDRR.

Besides production, CPDRR had strong collaborations with pharmaceutical industry in Slovenia and abroad (development of diagnostic tools, based on polyclonal antibodies for quality control, development of panels of monoclonal antibodies »à la carte«, know-how; nine projects and scientific elaborates for the industry so far).

All the time CPDRR has been involved in research activities in biomedical field in Slovenia and internationally with monoclonal antibodies as one of the main research lines (ten research projects and twelve PhDs were ran so far). We have our own animal facility (with permanent permission of appropriate veterinary authority), as well as recombinant antibody/protein facilities.

We are also an important partner of the University of Ljubljana, teaching students about theoretical and practical aspects of monoclonal antibody production and their use in research, diagnostics and in therapy on graduate and postgraduate levels.

Research activity

A number of monoclonal antibodies were developed, validated, produced, licensed and patented by CPDRR. Besides monoclonal antibodies against antigens of the blood group system AB0, they are directed against cytokines (TNF, p55, p75, MIF), potential new tumor markers and prion protein and its truncated form. In the last case, a panel of mouse monoclonal antibodies were developed in order to: 1) prepare a new generation of diagnostic kit, which was proposed to the EU Commission; 2) study the pathogenesis of the disease; 3) C-terminally truncated form of prion protein, PrP226*, was first described with the help of one of our monoclonal antibodies. In last years, there is a debate about its involvement in neurodegenerative diseases, especially in Alzheimer's disease. Besides development and validation of »in-house« immunological tests for IgA, anti-IgA and IgG determination, which are used in blood bank and diagnostic labs, our group is also developing tools for fully human monoclonal antibody production from immunised donors. A part of our activities is dedicated to recombinant Ab technology development with the main purpose to use the rAb as antigen binding domains in cell therapeutics such as adopted T-cells and stem cells.

Techniques available

  • protein/antigen expression and purification
  • mouse monoclonal antibody production
  • polyclonal antibody production
  • recombinant antibody production and expression in non-immune (stem) cells
  • antibody characterisation (western blot, dot blot, ELISA, flow cytometry and cell sorting, immunohistochemistry, immunocytochemistry, variable-region DNA sequencing)
  • monoclonal antibody purification (HPLC, including adaptation to serum-free media)
  • monoclonal antibody fragmentation
  • production under GLP
  • development and validation of ELISA tests
  • recombinant Ab technologies: rDNA, rRNA, rAb, CAR-T technology

Publications (2020-present)

  • GOLOB URBANC, Anja, RAJČEVIĆ, Uroš, STRMŠEK, Žiga, JERALA, Roman. Design of split superantigen fusion proteins for cancer immunotherapy. The Journal of Biological Chemistry, 2019, vol. 294, iss. 16, 6294-6305.
  • KOVAČ, Valerija, ČURIN-ŠERBEC, Vladka. Prion proteins without the glycophosphatidylinositol anchor: potential biomarkers in neurodegenerative diseases. Biomarker Insights, 2018, vol. 13, 1-5.
  • JAZBEC, Katerina, JEŽ, Mojca, SMREKAR, Boštjan, MICESKA, Simona, ROŽMAN, Jasmina Živa, ŠVAJGER, Urban, ZAVRŠNIK, Janja, MALOVRH, Tadej, ROŽMAN, Primož. Chimerism and gene therapy - lessons learned from non-conditioned murine bone marrow transplantation models. European Journal of Haematology, 2018, vol. 100, no. 4, 372-382.
  • RAZPOTNIK, Rok, NOVAK, Neža, ČURIN-ŠERBEC, Vladka, RAJČEVIĆ, Uroš. Targeting malignant brain tumors with antibodies. Frontiers in Immunology, 2017, vol. 8, 1-14.
  • KOVAČ, Valerija, ZUPANČIČ, Blaž, ILC, Gregor, PLAVEC, Janez, ČURIN-ŠERBEC, Vladka. Truncated prion protein PrP226* - a structural view on its role in amyloid diseas. Biochemical and Biophysical Research Communications, 2017, vol. 484, iss. 1, 45-50.
  • BOGOŽALEC KOŠIR, Alexandra, LUKAN, Tjaša, KUKOVEC, Mateja, SNOJ, Vivijana, MONTANIČ, Sendi, ČURIN-ŠERBEC, Vladka, RAJČEVIĆ, Uroš. New monoclonal antibodies against bilitranslocase as a diagnostic tool in determining the progress of clear cell renal cell carcinoma. Zdravniški vestnik - glasilo Slovenskega zdravniškega društva, 2017, vol. 86, iss. 5/6, 177-184.
  • KOVAČ, Valerija, HAFNER BRATKOVIČ, Iva, ČURIN-ŠERBEC, Vladka. Anchorless forms of prion protein - Impact of truncation on structure destabilization and prion protein conversion. Biochemical and Biophysical Research Communications, 2016, vol. 481, iss. 1/2, 1-6.
  • AMIN, Ladan, NGUYEN, Xuan T. A., ROLLE, Irene Giulia, D'ESTE, Elisa, GIACHIN, Gabriele, TRAN, Thanh, ČURIN-ŠERBEC, Vladka, COJOC, Dan, LEGNAME, Giuseppe. Characterization of prion protein function by focal neurite stimulation. Journal of Cell Science, 2016, vol. 129, no. 20, 3878-3891.
  • RONCADOR, Giovanna, ENGEL, Pablo, MAESTRE, Lorena, ANDERSON, Amanda P., CORDELL, Jacqueline L., CRAGG, Mark S., ČURIN-ŠERBEC, Vladka, JONES, Margaret, JURANIĆ LISNIĆ, Vanda, KREMER, Leonor, et al. The European antibody network's practical guide to finding and validating suitable antibodies for research. MAbs, 2016, vol. 8, iss. 1, 27-36.
  • FILIPPI, Antonio, PETRUSSA, Elisa, RAJČEVIĆ, Uroš, ČURIN-ŠERBEC, Vladka, PASSAMONTI, Sabina, RENZONE, Giovanni, SCALONI, Andrea, ZANCANI, Marco, VIANELLO, Angelo, BRAIDOT, Enrico. Flavonoid interaction with a chitinase from grape berry skin : protein identification and modulation of the enzymatic activity. Molecules, 2016, vol. 21, no. 10, 1-16.
  • PODERGAJS, Neža, MOTALN, Helena, RAJČEVIĆ, Uroš, VERBOVŠEK, Urška, KORŠIČ, Marjan, OBAD, Nina, ESPEDAL, Heidi, VITTORI, Miloš, HEROLD-MENDE, Christel, MILETIC, Hrvoje, BJERKVIG, Rolf, LAH TURNŠEK, Tamara. Transmembrane protein CD9 is glioblastoma biomarker, relevant for maintenance of glioblastoma stem cells. Oncotarget, 2016, vol. 7, no. 1, 593-609.
  • DIDONNA, Alessandro, COLJA VENTURINI, Anja, PRETNAR-HARTMAN, Katrina, VRANAC, Tanja, ČURIN-ŠERBEC, Vladka, LEGNAME, Giuseppe. Characterization of four new monoclonal antibodies against the distal N-terminal region of PrPC. Peer J, 2015, vol. 3. https://peerj.com/articles/811/.
  • JANEŽ, Nikolaja, KOKOŠIN, Andreja, ZALETEL, Eva, VRANAC, Tanja, KOVAČ, Jasna, VUČKOVIĆ, Darinka, SMOLE MOŽINA, Sonja, ČURIN-ŠERBEC, Vladka, ZHANG, Qijing, ACCETTO, Tomaž, PODGORNIK, Aleš, PETERKA, Matjaž. Identification and characterisation of new Campylobacter group III phages of animal origin. FEMS Microbiology Letters, 2014, no. 1, vol. 359, 64-71.
  • PERESSON, Carlo, RAJČEVIĆ, Uroš, MONTANIČ, Sendi, ČURIN-ŠERBEC, Vladka, et al. Involvement of mammalian bilitranslocase-like protein(s) in chlorophyll catabolism of Pisum sativum L. tissues. Journal of Bioenergetics and Biomembranes, 2014, vol. 46, 109-117.
  • LUKAN, Anja, ČERNILEC, Maja, VRANAC, Tanja, POPOVIĆ, Mara, ČURIN-ŠERBEC, Vladka. Regional distribution of anchorless prion protein, PrP226*, in the human brain. Prion, 2014, vol. 8, iss. 2, 1-7.
  • RAJČEVIĆ, Uroš, KNOL, Jaco C., PIERSMA, Sander, BOUGNAUD, Sebastien, FACK, Fred, SUNDLISAETER, Eirik, SØNDENAA, Karl, MYKLEBUST, Reidar, PHAM, Thang V., NICLOU, Simone P., et al. Colorectal cancer derived organotypic spheroids maintain essential tissue characteristics but adapt their metabolism in culture. Proteome Science, 2014, vol. 12. http://www.proteomesci.com/content/pdf/1477-5956-12-39.pdf.
  • ŠKRLJ, Nives, DREVENŠEK, Gorazd, HUDOKLIN, Samo, ROMIH, Rok, ČURIN-ŠERBEC, Vladka, DOLINAR, Marko. Recombinant single-chain antibody with the trojan peptide penetratin positioned in the linker region enables cargo transfer across the blood-brain barrier. Applied Biochemistry and Biotechnology 2013 (169): 159-169. doi: 10.1007/s12010-012-9962-7.
  • PODERGAJS, Neža, BREKKA, Narve, RADLWIMMER, Bernhard, HEROLD-MENDE, Christel, TALASILA, Krishna M., TIEMANN, Katja, RAJČEVIĆ, Uroš, LAH TURNŠEK, Tamara, BJERKVIG, Rolf, MILETIC, Hrvoje. Expansive growth of two glioblastoma stem-like cell lines is mediated by bFGF and not by EGF. In: Articles from 7th Conference of experimental and translational oncology, [April, 20-24, 2013, Portorož], (Radiology and Oncology, vol. 47, no. 4). Ljubljana: Association of Radiology and Oncology, 2013: 330-337. http://www.degruyter.com/view/j/raon.2013.47.issue-4/raon-2013-0063/raon-2013-0063.xml, doi: 10.2478/raon-2013-0063.
  • DVORAKOVA, Eva, VRANAC, Tanja, JANOUSKOVA, Olga, ČERNILEC, Maja, KOREN, Simon, LUKAN, Anja, NOVÁKOVÁ, Jana, MATEJ, Radoslav, HOLADA, Karel, ČURIN-ŠERBEC, Vladka. Detection of the GPI-anchorless prion protein fragment PrP226* in human brain. BMC Neurology 2013 (13). http://www.biomedcentral.com/1471-2377/13/126, doi: 10.1186/1471-2377-13-126.
  • PETERSEN, Kjell, RAJČEVIĆ, Uroš, RAHIM, Siti Aminah Abdul, JONASSEN, Inge, KALLAND, Karl-Henning, JIMENEZ, Connie R., BJERKVIG, Rolf, NICLOU, Simone P. Gene set based integrated data analysis reveals phenotypic differences in a brain cancer model. PloS one 2013 (8): 1-11. e-68288. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0068288, doi: 10.1371/journal.pone.0068288.
  • MONTANIČ, Sendi, TERDOSLAVICH, Michela, RAJČEVIĆ, Uroš, DE LEO, Luigina, BONIN, Serena, ČURIN-ŠERBEC, Vladka, PASSAMONTI, Sabina. Development and characterization of a novel mAb against bilitranslocase - a new biomarker of renal carcinoma. Radiology and Oncology 2013 (47): 128-137. doi: 10.2478/raon-2013-0026.
  • ŠNAJDER, Marko, VILFAN, Tanja, ČERNILEC, Maja, RUPREHT, Ruth, POPOVIĆ, Mara, JUNTES, Polona, ČURIN-ŠERBEC, Vladka, POKLAR ULRIH, Nataša. Enzymatic degradation of PrPSc by a protease secreted from Aeropyrum pernix K1. PloS one 2012 (7): 1-12. e39548. doi: 10.1371/journal.pone.0039548.
  • MORI, Jerneja, VRANAC, Tanja, SMREKAR, Boštjan, ČERNILEC, Maja, ČURIN-ŠERBEC, Vladka, HORVAT, Simon, IHAN, Alojz, BENČINA, Mojca, JERALA, Roman. Chimeric flagellin as the self-adjuvanting antigen for the activation of immune response against Helicobacter pylori. Vaccine 2012 (30): 5856-5863. http://www.sciencedirect.com/science/article/pii/S0264410X12010134, doi: 10.1016/j.vaccine.2012.07.011.
  • DELNERI, A., FRANCA, Raffaella, TERDOSLAVICH, Michela, MONTANIČ, Sendi, ČURIN-ŠERBEC, Vladka, TRAMER, Federica, FRANCESE, Marco, PASSAMONTI, Sabina. Identification and functional characterization of bilitranslocase in sea-bass (Dicentrarchus labrax) hepatopancreas. Analytical Letters 2011 (44): 2887-2900. doi: 10.1080/00032719.2011.582548.
  • KOSMAČ, Miha, KOREN, Simon, GIACHIN, Gabriele, ČURIN-ŠERBEC, Vladka, et al. Epitope mapping of a PrP(Sc)-specific monoclonal antibody : identification of a novel C-terminally truncated prion fragment. Molecular Immunology 2011 (48): 746-750.
  • KOSMAČ, Miha, AVČIN, Tadej, TOPLAK, Nataša, SIMONINI, Gabriele, CIMAZ, Rolando, ČURIN-ŠERBEC, Vladka. Exploring the binding sites of anti-infliximab antibodies in pediatric patients with rheumatic diseases treated with infliximab. Pediatric Research 2011 (69): 243-248. doi: 10.1203/PDR.0b013e318208451d.
  • ŠKRLJ, Nives, VRANAC, Tanja, POPOVIĆ, Mara, ČURIN-ŠERBEC, Vladka, DOLINAR, Marko. Specific binding of the pathogenic prion isoform: development and characterization of a humanized single-chain variable antibody fragment. PloS one 2011, vol. 6, no. 1, art. no. e15783 (9 str.). http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0015783, doi: 10.1371/journal.pone.0015783.
  • GOPLEN, Dorota, RAJČEVIĆ, Uroš, et al. [alpha]B-crystallin is elevated in highly infiltrative apoptosis-resistant glioblastoma cells. The American Journal of Pathology 2010 (177): 1618-1628. http://dx.doi.org/10.2353/ajpath.2010.090063, doi: 10.2353/ajpath.2010.090063.
  • ŠKRLJ, Nives, ČURIN-ŠERBEC, Vladka, DOLINAR, Marko. Single-chain Fv antibody fragments retain binding properties of the monoclonal antibody raised against peptide P1 of the human prion protein. Applied Biochemistry and Biotechnology 2010 (160): 1808-1821. http://www.springerlink.com/content/n72368781x356488/fulltext.pdf, doi: 10.1007/s12010-009-8699-4.
  • VRANAC, Tanja, BRESJANAC, Mara. Metabolic aspects of prion diseases : an overview. Current Drug Targets 2010 (11): 1207-1217.
  • LAH TURNŠEK, Tamara, NANNI, Isabelle, TRINKAUS, Miha, METELLUS, Philipe, DUSSERT, Christophe, RIDDER, Leo de, RAJČEVIĆ, Uroš, BLEJEC, Andrej, MARTIN, Pierre-Marie. Toward understanding recurrent meningioma: the potential role of lysosomal cysteine proteases and their inhibitors. Journal of Neurosurgery 2010 (112): 940-950. http://dx.doi.org/10.3171/2009.7.JNS081729, doi: 10.3171/2009.7.JNS081729.
  • COLJA VENTURINI, Anja, BRESJANAC, Mara, VRANAC, Tanja, KOREN, Simon, NARAT, Mojca, POPOVIĆ, Mara, ČURIN-ŠERBEC, Vladka. Anti-idiotypic antibodies : a new approach in prion research. BMC Immunology 2009, vol. 10, article 16, on line. http://www.biomedcentral.com/1471-2172/10/16, doi: 10.1186/1471-2172-10-16.
  • RAJČEVIĆ, Uroš, NICLOU, Simone P., JIMENEZ, Connie R. Proteomics strategies for target identification and biomarker discovery in cancer. Frontiers in Bioscience 2009 (14): 3292-3303. http://www.bioscience.org/current/vol14.htm, doi: 10.2735/3452.
  • GHIELMETTI, Mascia, VRANAC, Tanja, ČURIN-ŠERBEC, Vladka. Prion protein peptides as vaccines. Mini Reviews in Medicinal Chemistry 2009 (9): 470-480.
  • RAJČEVIĆ, Uroš, et al. iTRAQ based proteomic profiling reveals increased metabolic activity and cellular crosstalk in angiogenic compared to invasive glioblastoma phenotype. Molecular & Cellular Proteomics 2009 (8): 2595-2612. http://dx.doi.org/10.1074/mcp.M900124-MCP200, doi: 10.1074/mcp.M900124-MCP200.
  • KOREN, Simon, KOSMAČ, Miha, COLJA VENTURINI, Anja, MONTANIČ, Sendi, ČURIN-ŠERBEC, Vladka. Antibody variable-region sequencing as a method for hybridoma cell-line authentication. Applied Microbiology and Biotechnology 2008 (78): 1071-1078. doi: 10.1007/s00253-008-1386-5.
  • TRONTELJ, Katja, REBERŠEK, Matej, KANDUŠER, Maša, ČURIN-ŠERBEC, Vladka, ŠPROHAR, Marjana, MIKLAVČIČ, Damijan. Optimization of bulk cell electrofusion in vitro for production of human-mouse heterohybridoma cells. Bioelectrochemistry 2008 (74): 124-129. 10.1016/j.bioelechem.2008.06.003.