Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes
Institut für Virologie
Institutsdirektorin: Prof. Dr. med. Sigrun Smola
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Arbeitsgruppe EBV - Prof. Dr. rer. nat. Friedrich Grässer

Epstein-Barr Viruspartikel im Elektronenmikroskop

Inhalt


Forschungsgebiete

Wir untersuchen den Beitrag des Epstein-Barr Virus (EBV) bei der Entstehung verschiedener humaner Tumoren.  Das Epstein-Barr Virus infiziert symptomlos mehr als 95% aller Erwachsenen weltweit und verbleibt wie alle Herpesviren als latentes Virus lebenslang in Gedächtnis-Lymphozyten der infizierten Person erhalten. Unter Immunsuppression, bei genetischer Veranlagung oder bei bestimmten Umweltbedingungen kann das Virus jedoch Tumore verursachen. Ziel ist es, den Beitrag von virus-kodierten microRNAs und virus-kodierter Proteine bei der Tumorentstehung aufzudecken und mögliche therapeutische Strategien zu entwickeln.

Schwerpunkte unserer Forschung sind:

  • Die Funktion virus-kodierter und virus-regulierter zellulärer microRNAs bei der Tumorentstehung.
  • Die Arginin-Methylierung des virus-kodierten Kernantigens EBNA2.
  • Die Deregulation zellulärer microRNAs beim Prostata Karzinom.

Mitarbeiter

Leitung:


Prof. Dr. Friedrich Grässer

Tel. +496841/162-3983 (Office)

+496841/162-3940 (Lab)
Fax +496841/1623980
Mail:

 

Arbeitsgruppe:

 


Publikationen

  • Wyler E, Menegatti J, Franke V, Kocks C, Boltengagen A, Hennig T, Theil K, Rutkowski A, Ferrai C, Baer L, Kermas L, Friedel C, Rajewsky N, Akalin A, Dölken L, Grässer F, Landthaler M.
    Widespread activation of antisense transcription of the host genome during herpes simplex virus 1 infection.
    Genome Biol. 2017 Oct 31;18(1):209. doi: 10.1186/s13059-017-1329-5. (https://www.ncbi.nlm.nih.gov/pubmed/29089033)
  • Schwind L, Nalbach L, Zimmer AD, Kostelnik KB, Menegatti J, Grässer F, Götz C, Montenarh M.
    Quinalizarin inhibits adipogenesis through down-regulation of transcription factors and microRNA modulation.
    Biochim Biophys Acta. 2017 Sep 28. pii: S0304-4165(17)30318-5. doi: 10.1016/j.bbagen.2017.09.018. [Epub ahead of print] (https://www.ncbi.nlm.nih.gov/pubmed/28964816)
  • Hiresh Ayoubian, Thomas Fröhlich, Dagmar Pogodski, Andrew Flatley, Elisabeth Kremmer, Aloys Schepers, Regina Feederle, Georg J. Arnold, and Friedrich A. Grässer.
    Antibodies against the mono-methylated arginine-glycine repeat (MMA-RG) of the Epstein-Barr virus nuclear antigen 2 (EBNA2) identify potential cellular proteins targeted in viral transformation.
    Journal of General Virology, 2017 (https://www.ncbi.nlm.nih.gov/pubmed/28758620)
  • Marthaler AM, Podgorska M, Feld O, Fingerle A, Knerr-Rupp K, Grässer F, Smola H, Roemer K, Ebert E, Kim YJ, Bohle RM, Müller CSL, Reichrath J, Vogt T, Malejczyk M, Majewski S, Smola S.
    Identification of C/EBPα as a novel target of the HPV8 E6 protein regulating miR-203 in human keratinocytes.
    PLoS Pathogens. 2017 (https://doi.org/10.1371/journal.ppat.1006406)
  • Alles J, Ludwig N, Rheinheimer S, Leidinger P, Grässer FA, Keller A, Meese E.
    MiR-148aimpairs Ras/ERK signaling in B lymphocytes by targeting SOS proteins.
    Oncotarget. 2017 May 7. doi: 10.18632/oncotarget.17662. [Epub ahead of print]
  • Sarah Mizielinska, Charlotte E. Ridler, Rubika Balendra, Annora Thoeng, Nathan S. Woodling, Friedrich A. Grässer, Vincent Plagnol, Tammaryn Lashley, Linda Partridge and Adrian M. Isaacs.

    Bidirectional nucleolar dysfunction in C9orf72 frontotemporal lobar degeneration.

    Acta Neuropathol Commun. 2017; 5: 29. Published online 2017 Apr 18. doi:  10.1186/s40478-017-0432
  • Szczyrba J, Jung V, Beitzinger M, Nolte E, Wach S, Hart M, Sapich S, Wiesehöfer M, Taubert H, Wennemuth G, Eichner N, Stempfl T, Wullich B, Meister G and Grässer FA.
    Analysis of Argonaute Complex Bound mRNAs in DU145 Prostate Carcinoma Cells Reveals New miRNA Target Genes.
    Prostate Cancer,
    Volume 2017 (2017), Article ID 4893921, 12 pages
  • Hasler D, Lehmann G, Murakawa Y, Klironomos F, Jakob L, Grässer FA, Rajewsky N, Landthaler M, Meister G.
    The Lupus Autoantigen La Prevents Mis-channeling of tRNA Fragments into the Human MicroRNA Pathway.
    Mol Cell. 2016 Jul 7;63(1):110-24. doi: 10.1016/j.molcel.2016.05.026. Epub 2016 Jun 23.
  • Hart M, Rheinheimer S, Leidinger P, Backes C, Menegatti J, Fehlmann T, Grässer F, Keller A, Meese E.
    Identification of miR-34a-target interactions by a combined network based and experimental approach.
    Oncotarget. 2016 Jun 7;7(23):34288-99. doi: 10.18632/oncotarget.9103.
  • Backes C, Meder B, Hart M, Ludwig N, Leidinger P, Vogel B, Galata V, Roth P, Menegatti J, Grässer F, Ruprecht K, Kahraman M, Grossmann T, Haas J, Meese E, Keller A.
    Prioritizing and selecting likely novel miRNAs from NGS data.
    Nucleic Acids Res. 2016 Apr 7;44(6):e53. doi: 10.1093/nar/gkv1335. Epub 2015 Dec 3.
  • Julia Alles, Jennifer Menegatti, Natalie Motsch, Martin Hart, Norbert Eichner, Richard Rinhardt, Gunter Meister and Friedrich A. Grässer
    miRNA expression profiling of Epstein–Barr virus-associated NKTL cell lines by Illumina deep sequencing.
    FEBS OpenBIO, 2016 Feb 27;6(4):251-63. doi: 10.1002/2211-5463, 12027.
  • Julia Alles, Daniele Hasler, Syed Mohammad Ali Kazmi, Mathias Tesson, Andrew Hamilton, Linda Schlegel, Stefanie Marx, Norbert Eichner, Richard Reinhardt, Gunter Meister, Joanna B. Wilson and Friedrich A. Grässer
    Epstein-Barr Virus EBER Transcripts Affect miRNA-Mediated Regulation of Specific Targets and Are Processed to Small RNA Species.
    Non-Coding RNA, 2015, 1(3), 170-191
  • Ian R. A. Mackenzie, Petra Frick, Friedrich A. Grässer, Tania F. Gendron, Leonard Petrucelli, Neil R., Cashman, Dieter Edbauer, Elisabeth Kremmer, Johannes Prudlo, Dirk Troost, Manuela Neumann
    Quantitative analysis and clinico-pathological correlations of different dipeptide repeat Protein pathologies in C9ORF72 mutation carriers
    Acta Neuropathol., 2015 Sep 15. [Epub ahead of print]
  • Heyne K, Kölsch K, Bruand M, Kremmer E, Grässer FA, Mayer J, Roemer K.
    Np9, a cellular protein of retroviral ancestry restricted to human, chimpanzee and gorilla, binds and regulates ubiquitin ligase MDM2.
    Cell Cycle, 2015 Aug 18;14(16):2619-33. Epub 2015 Jun 23.
  • Schludi MH, May S, Grässer FA, Rentzsch K, Kremmer E, Küpper C, Klopstock T; German Consortium for Frontotemporal Lobar Degeneration; Bavarian Brain Banking Alliance, Arzberger T, Edbauer D.
    Distribution of dipeptide repeat proteins in cellular models and C9orf72 mutation cases suggests link to transcriptional silencing.
    Acta Neuropathol., 2015 Oct;130(4):537-55. Epub 2015 Jun 18. Erratum in: Acta Neuropathol. 2015 Oct;130(4):557-8.
  • Teng Feng, Johanna Dzieran, Xing Gu, Silke Marhenke, Arndt Vogel, Keigo Machida, Thomas S Weiss, Petra Rümmele, Otto Kollmar, Patrick Hoffmann, Friedrich Graesser, Heike Allgayer, Jasmin Fabian, Hong Lei Weng, Andreas Teufel, Thorsten Maass,Christoph Meyer, Ulrich Lehmann, Cheng Zhu, Peter R Mertens, Chun Fang Gao, Steven Dooley and Nadja M Meindl-Beinker.
    Smad7 regulates compensatory hepatocyte proliferation in damaged mouse liver and positively relates to better clinical outcome in human hepatocellular carcinoma.
    Clinical Science (2015) 128, 761-774.
  • Koganti S, Hui-Yuen J, McAllister S, Gardner B, Grasser F, Palendira U, Tangye SG, Freeman AF, Bhaduri-McIntosh S.
    STAT3 interrupts ATR-Chk1 signaling to allow oncovirus-mediated cell proliferation.
    Proc Natl Acad Sci USA. 2014 Apr 1;111(13):4946-51. doi: 10.1073/pnas.1400683111. Epub 2014 Mar 17.
  • Rubie C, Kruse B, Frick VO, Kölsch K, Ghadjar P, Wagner M, Grässer F, Wagenpfeil S, Glanemann M.
    Chemokine receptor CCR6 Expression is regulated by mir-518a-5p in colorectal cancer cells.
    J Transl Med
    , 2014 Feb 21;12(1):48. (http://www.ncbi.nlm.nih.gov/pubmed/24559209)
  • Hart M, Nolte E, Wach S, Szczyrba J, Taubert H, Rau T, Hartmann A, Grässer FA, Wullich B.
    Comparative microRNA profiling of prostate carcinomas with increasing tumor stage by deep-sequencing.
    Molecular Cancer Research, 2013.
  • Hart M, Wach S, Nolte E, Szczyrba J, Menon R, Taubert H, Hartmann A, Stoehr R, Wieland W, Grässer FA, Wullich B.
    The proto-oncogene ERG is a target of microRNA miR-145 in prostate cancer.
    FEBS, 2013.
  • Kwanhian W, Lenze D, Alles J, Motsch N, Barth S, Döll C, Imig J, Hummel M, Tinguely M, Trivedi P, Lulitanond V, Meister G, Renner C, Grässer FA.
    MicroRNA-142 is Mutated in About 20% of Diffuse Large B-Cell Lymphoma (DLBCL).
    Cancer Medicine, epub on September, 18, 2012. http://onlinelibrary.wiley.com/doi/10.1002/cam4.29/abstract
  • Motsch N, Alles J, Imig J, Zhu J, Barth S, et al. (2012)
    MicroRNA Profiling of Epstein-Barr Virus-Associated NK/T-Cell Lymphomas by Deep Sequencing.
    PLoS ONE 7(8): e42193. doi:10.1371/journal.pone.0042193
  • Gross H, Hennard C, Masouris I, Cassel C, Barth S, et al. (2012)
    Binding of the Heterogeneous Ribonucleoprotein K (hnRNP K) to the Epstein-Barr Virus Nuclear Antigen 2 (EBNA2) Enhances Viral LMP2A Expression.
    PLoS ONE 7(8): e42106. doi:10.1371/journal.pone.0042106
  • Szczyrba J, Nolte E, Hart M, Döll C, Wach S, Taubert H, Keck B, Kremmer E, Stöhr R, Hartmann A, Wieland W, Wullich B, Grässer FA.
    Identification of ZNF217, hnRNP-K, VEGF-A and IPO7 as targets for microRNAs that are downregulated in prostate carcinoma.
    Int J Cancer. 2012 Jul 19
  • Kremmer E, Meyer K, Grässer FA, Flatley A, Kösters M, Luppa PB, Krämer PM.
    A new strategy for the development of monoclonal antibodies for the determination of human procalcitonin in serum samples.
    Analytical & Bioanalytical Chemistry, 2011, epub on October, 18.
  • Alkassar M, Gärtner B, Roemer K, Graesser F, Rommelaere J, Kaestner L, Haeckel I, Graf N.
    The combined effects of oncolytic reovirus plus Newcastle disease virus and reovirus plus parvovirus on U87 and U373 cells in vitro and in vivo.
    J Neurooncol, 2011 May 24.
  • Barth S, Meister G, Graesser FA.
    EBV-encoded miRNAs.
    BBA Gene Regulatory Mechanisms 2011, epub on May, 24.
  • Szczyrba J, Nolte E, Wach S, Kremmer E, Stöhr R, Hartmann A, Wieland W, Wullich B, Grässer FA.
    Downregulation of Sec23A protein by miRNA-375 in prostate carcinoma.
    Mol. Cancer Research 2011, epub on May, 18.
  • Wach S, Nolte E, Szczyrba J, Stöhr R, Hartmann A, Orntoft T, Dyrskjøt L, Eltze E, Wieland W, Keck B, Ekici AB, Grässer F, Wullich B.
    MicroRNA profiles of prostate carcinoma detected by multiplatform microRNA screening.
    Int J Cancer. 2011 Mar 11. doi: 10.1002/ijc.26064. [Epub ahead of print]
  • Imig J, Motsch N, Zhu JY, Barth S, Okoniewski M, Reineke T, Tinguely M, Faggioni A, Trivedi P, Meister G, Renner C, Grässer FA.
    MicroRNA profiling in Epstein-Barr virus-associated B-cell lymphoma.
    Nucleic Acids Res. 2011 Mar 1;39(5):1880-93. Epub 2010 Nov 9.
  • Gross H, Barth S, Palermo RD, Mamiani A, Hennard C, Zimber-Strobl U, West MJ, Kremmer E, Grässer FA. Asymmetric Arginine dimethylation of Epstein-Barr virus nuclear antigen 2 promotes DNA targeting.
    Virology 2010; 397:299-310.
  • Szczyrba J, Löprich E, Wach S, Jung V, Unteregger G, Barth S, Grobholz R, Wieland W, Stöhr R, Hartmann A, Wullich B, Grässer F.
    The MicroRNA Profile of Prostate Carcinoma Obtained by Deep Sequencing.
    Mol Cancer Res 2010; 8:529-38.
  • Dolken L, Malterer G, Erhard F, Kothe S, Friedel CC, Suffert G, Marcinowski L, Motsch N, Barth S, Beitzinger M, Lieber D, Bailer SM, Hoffmann R, Ruzsics Z, Kremmer E, Pfeffer S, Zimmer R, Koszinowski UH, Grässer F, Meister G, Haas J.
    Systematic analysis of viral and cellular microRNA targets in cells latently infected with human gamma-herpesviruses by RISC immunoprecipitation assay.
    Cell host & microbe 2010; 7:324-34
  • Zhu JY, Pfuhl T, Motsch N, Barth S, Nicholls J, Grässer F, Meister G.
    Identification of novel Epstein-Barr virus microRNA genes from nasopharyngeal carcinomas.
    Journal of virology 2009; 83:3333-41.
  • Nandy C, Mrazek J, Stoiber H, Grässer FA, Huttenhofer A, Polacek N.
    Epstein-barr virus-induced expression of a novel human vault RNA.
    Journal of molecular biology 2009; 388:776-84.
  • Barth S, Pfuhl T, Mamiani A, Ehses C, Roemer K, Kremmer E, Jaker C, Hock J, Meister G, Grässer FA.
    Epstein-Barr virus-encoded microRNA miR-BART2 down-regulates the viral DNA polymerase BALF5.
    Nucleic acids research 2008; 36:666-75.
  • Pfuhl T, Mamiani A, Durr M, Welter S, Stieber J, Ankara J, Liss M, Dobner T, Schmitt A, Falkai P, Kremmer E, Jung V, Barth S, Grässer FA.
    The LARK/RBM4a protein is highly expressed in cerebellum as compared to cerebrum.
    Neuroscience letters 2008; 444:11-5.
  • Mrazek J, Kreutmayer SB, Grässer FA, Polacek N, Huttenhofer A.
    Subtractive hybridization identifies novel differentially expressed ncRNA species in EBV-infected human B cells.
    Nucleic acids research 2007; 3:3.
  • Motsch N, Pfuhl T, Mrazek J, Barth S, Grässer FA.
    Epstein-Barr Virus-encoded latent membrane protein 1 (LMP1) induces the expression of the cellular microRNA miR-146a.
    RNA biology 2007; 4:131-7.
  • Pfeffer S, Sewer A, Lagos-Quintana M, Sheridan R, Sander C, Grässer FA, van Dyk LF, Ho CK, Shuman S, Chien M, Russo JJ, Ju J, Randall G, Lindenbach BD, Rice CM, Simon V, Ho DD, Zavolan M, Tuschl T.
    Identification of microRNAs of the herpesvirus family.
    Nat Methods 2005; 2:269-76.
  • Pfeffer S, Zavolan M, Grässer FA, Chien M, Russo JJ, Ju J, John B, Enright AJ, Marks D, Sander C, Tuschl T.
    Identification of virus-encoded microRNAs.
    Science (New York, NY 2004; 304:734-6.
  • Barth S, Liss M, Voss MD, Dobner T, Fischer U, Meister G, Grässer FA.
    Epstein-Barr virus nuclear antigen 2 binds via its methylated arginine- glycine repeat to the survival motor neuron protein.
    Journal of virology 2003; 77:5008-13.

Links

Kontakt

Prof. Dr. Friedrich Grässer
Institut für Virologie
Gebäude 47
Universitätsklinkum des Saarlandes
66421 Homburg/Saar
Tel. 06841-1623983

Fax. 06841-1623980

Friedrich.Graesser @uks.eu