Institute for Pharmaceutical Biology -
Prof. Dr. Rolf Marschalek

>

Expertise

• Genomic instability mediated through transposable and retrotransposable elements
  
• Retrotransposons and other mobile genetic elements
  
• New strategies to improve vector integration specificity in gene therapy
  
• Target identification for known and novel active substances
  
• Acute leukaemia in humans (hematooncology)
  
• Pathomolecular mechanisms in the formation of leukaemia
  
• Genetic instabilities
  
• Mechanisms in gene regulation – expression profiling
  
• Diagnostic of human diseases
  
  

>

Resources and Abilities

• Production of monoclonal antibodies
  
• 2D-gel electrophoresis
  
• mass spectrometry (in collaboration with Prof. Michael Karas)
  
• functional test systems
  
• exploration of novel targets
  
• identification of novel tissue specific target proteins for known and novel active substances (effects, metabolism, elimination)
  
• DNA sequencing, cloning transfection/ transformation
  
• Eukaryotic cell cultures (yeast, mouse, human)
  
• Protein interactions (human, yeast)
  
• Protein biochemistry/ protein structure/ molecular mechanisms (human)
  
• expression of recombinant proteins in bacteria and human cell culture
  Molecular diagnostic with PCR and FACS
  
  

>

Staff:

• Dr. Ilse Zündorf (monoclonal antibodies)
  
  

>

Publications (last 5 years)

• Soler G, Radford I, Meyer C, Marschalek R, Brouzes C, Ghez D, Romana S, Berger R: MLL insertion with MLL-MLLT3 gene fusion in acute leukemia: case report and review of the literature. Cancer Genet Cytogenet 2008; 183: 53-59.
  
• Metzler M, Staege MS, Harder L, Mendelova D, Zuna J, Fronkova E, Meyer C, Flohr T, Bednarova D, Harbott J, Langer T, Gesk S, Trka J, Siebert R, Dingermann T, Marschalek R, Niemeyer C, Rascher W: Inv(11)(q21q23) fuses MLL to the Notch co-activator mastermind-like 2 in secondary T-cell acute lymphoblastic leukemia. Leukemia 2008; Mar 13: Epub ahead of print.
  
• Dingermann T: Recombinant therapeutic proteins: production platforms and challenges. Biotechnol 2008; J 3: 90-97.
  
• Chung T, Siol O, Dingermann T, Winckler T: Protein interactions involved in tRNA gene-specific integration of Dictyostelium discoideum non-long terminal repeat retrotransposon TRE5-A. Mol Cell Biol 2007; 27: 8492-8501.
  
• Choi WT, Folsom MR, Azim MF, Meyer C, Kowarz E, Marschalek R, Timchenko NA, Naeem RC, Lee DA: C/EBPbeta suppression by interruption of CUGBP1 resulting from a complex rearrangement of MLL. Cancer Genet Cytogenet 2007; 177: 108-114.
  
• Zuna J, Cavé H, Eckert C, Szczepanski T, Meyer C, Mejstrikova E, Fronkova E, Muzikova K, Clappier E, Mendelova D, Boutard P, Schrauder A, Sterba J, Marschalek R, van Dongen JJ, Hrusak O, Stary J, Trka J: Childhood secondary ALL after ALL treatment. Leukemia 2007; 21: 1431-1435.
  
• Lechtken A, Hörnig M, Werz O, Corvey N, Zündorf I, Dingermann T, Brandes R, Steinhilber D: Extracellular signal-regulated kinase-2 phosphorylates RORalpha4 in vitro. Biochem Biophys Res Commun 2007; 358: 890-896.
  
• Kowarz E, Burmeister T, Lo Nigro L, Jansen MW, Delabesse E, Klingebiel T, Dingermann T, Meyer C, Marschalek R: Complex MLL rearrangements in t(4;11) leukemia patients with absent AF4.MLL fusion allele. Leukemia 2007; 21: 1232-1238.
  
• Schneppenheim R, Castaman G, Federici AB, Kreuz W, Marschalek R, Oldenburg J, Oyen F, Budde U: A common 253-kb deletion involving VWF and TMEM16B in German and Italian patients with severe von Willebrand disease type 3. J Thromb Haemost 2007; 5: 722-728.
  
• Jansen MW, Corral L, van der Velden VH, Panzer-Grümayer R, Schrappe M, Schrauder A, Marschalek R, Meyer C, den Boer ML, Hop WJ, Valsecchi MG, Basso G, Biondi A, Pieters R, van Dongen JJ: Immunobiological diversity in infant acute lymphoblastic leukemia is related to the occurrence and type of MLL gene rearrangement. Leukemia 2007; 21: 633-641.
  
• Meyer C, Burmeister T, Strehl S, Schneider B, Hubert D, Zach O, Haas O, Klingebiel T, Dingermann T, Marschalek R: Spliced MLL fusions: a novel mechanism to generate functional chimeric MLL-MLLT1 transcripts in t(11;19)(q23;p13.3) leukemia. Leukemia 2007; 21: 588-590.
  
• Gaussmann A, Wenger T, Eberle I, Bursen A, Bracharz S, Herr I, Dingermann T, Marschalek R: Combined effects of the two reciprocal t(4;11) fusion proteins MLL.AF4 and AF4.MLL confer resistance to apoptosis, cell cycling capacity and growth transformation. Oncogene 2007; 26: 3352-3363.
  
• Scharf S, Zech J, Bursen A, Schraets D, Oliver PL, Kliem S, Pfitzner E, Gillert E, Dingermann T, Marschalek R: Transcription linked to recombination: a gene-internal promoter coincides with the recombination hot spot II of the human MLL gene. Oncogene 2007; 26: 1361-1371.
  
• Rau O, Wurglics M, Dingermann T, Abdel-Tawab M, Schubert-Zsilavecz M: Screening of herbal extracts for activation of the human peroxisome proliferator-activated receptor. Pharmazie 2006; 61: 952-956.
  
• Schaap P, Winckler T, Nelson M, Alvarez-Curto E, Elgie B, Hagiwara H, Cavender J, Milano-Curto A, Rozen DE, Dingermann T, Mutzel R, Baldauf SL: Molecular phylogeny and evolution of morphology in the social amoebas. Science 2006; 314: 661-663.
  
• Strehl S, König M, Meyer C, Schneider B, Harbott J, Jäger U, von Bergh AR, Loncarevic IF, Jarosova M, Schmidt HH, Moore SD, Marschalek R, Haas OA: Molecular dissection of t(11;17) in acute myeloid leukemia reveals a variety of gene fusions with heterogeneous fusion transcripts and multiple splice variants. Genes Chromosomes Cancer 2006; 45: 1041-1049.
  
• Siol O, Boutliliss M, Chung T, Glöckner G, Dingermann T, Winckler T: Role of RNA polymerase III transcription factors in the selection of integration sites by the dictyostelium non-long terminal repeat retrotransposon TRE5-A. Mol Cell Biol 2006; 26: 8242-8251.
  
• Meyer C, Kowarz E, Schneider B, Oehm C, Klingebiel T, Dingermann T, Marschalek R: Genomic DNA of leukemic patients: target for clinical diagnosis of MLL rearrangements. Biotechnol 2006; J 1: 656-663.
  
• Attarbaschi A, Mann G, König M, Steiner M, Strehl S, Schreiberhuber A, Schneider B, Meyer C, Marschalek R, Borkhardt A, Pickl WF, Lion T, Gadner H, Haas OA, Dworzak MN: Mixed lineage leukemia-rearranged childhood pro-B and CD10-negative pre-B acute lymphoblastic leukemia constitute a distinct clinical entity. Clin Cancer Res 2006; 12: 2988-2994.
  
• Burjanivova T, Madzo J, Muzikova K, Meyer C, Schneider B, Votava F, Marschalek R, Stary J, Trka J, Zuna J: Prenatal origin of childhood AML occurs less frequently than in childhood ALL. BMC Cancer 2006; 6: 100.
  
• Dingermann T, Zündorf I: Macromolecular immunosuppressants. Biotechnol J 2006; 1: 47-57.
  
• Rau O, Wurglics M, Paulke A, Zitzkowski J, Meindl N, Bock A, Dingermann T, Abdel-Tawab M, Schubert-Zsilavecz M: Carnosic acid and carnosol, phenolic diterpene compounds of the labiate herbs rosemary and sage, are activators of the human peroxisome proliferator-activated receptor gamma. Planta Med 2006; 72: 881-887.
  
• Lechtken A, Zündorf I, Dingermann T, Firla B, Steinhilber D. Overexpression, refolding, and purification of polyhistidine-tagged human retinoic acid related orphan receptor RORalpha4. Protein Expr Purif 2006; 49:114-120.
  
• Siol O, Dingermann T, Winckler T: The C-module DNA-binding factor mediates expression of the dictyostelium aggregation-specific adenylyl cyclase ACA. Eukaryot Cell 2006; 5: 658-664.
  
• Meyer C, Schneider B, Jakob S, Strehl S, Attarbaschi A, Schnittger S, Schoch C, Jansen MW, van Dongen JJ, den Boer ML, Pieters R, Ennas MG, Angelucci E, Koehl U, Greil J, Griesinger F, Zur Stadt U, Eckert C, Szczepa?ski T, Niggli FK, Schäfer BW, Kempski H, Brady HJ, Zuna J, Trka J, Nigro LL, Biondi A, Delabesse E, Macintyre E, Stanulla M, Schrappe M, Haas OA, Burmeister T, Dingermann T, Klingebiel T, Marschalek R: The MLL recombinome of acute leukemias. Leukemia 2006; 20: 777-784.
  
• Burmeister T, Marschalek R, Schneider B, Meyer C, Gökbuget N, Schwartz S, Hoelzer D, Thiel E: Monitoring minimal residual disease by quantification of genomic chromosomal breakpoint sequences in acute leukemias with MLL aberrations. Leukemia 2006; 20: 451-457.
  
• Wihler C, Schäfer S, Schmid K, Deemer EK, Münch G, Bleich M, Busch AE, Dingermann T, Somoza V, Baynes JW, Huber J: Renal accumulation and clearance of advanced glycation end-products in type 2 diabetic nephropathy: effect of angiotensin-converting enzyme and vasopeptidase inhibition. Diabetologia 2005; 48: 1645-1653.
  
• Teuffel O, Betts DR, Thali M, Eberle D, Meyer C, Schneider B, Marschalek R, Trakhtenbrot L, Amariglio N, Niggli FK, Schäfer BW: Clonal expansion of a new MLL rearrangement in the absence of leukemia. Blood 2005; 105:4151-4152.
  
• Meyer C, Schneider B, Reichel M, Angermueller S, Strehl S, Schnittger S, Schoch C, Jansen MW, van Dongen JJ, Pieters R, Haas OA, Dingermann T, Klingebiel T, Marschalek R: Diagnostic tool for the identification of MLL rearrangements including unknown partner genes. Proc Natl Acad Sci U S A 2005; 102:449-54. Epub 2004 Dec 30.
  
• Kracht T, Schrappe M, Strehl S, Reiter A, Elsner HA, Trka J, Cario G, Viehmann S, Harbott J, Borkhardt A, Metzler M, Langer T, Repp R, Marschalek R, Welte K, Haas OA, Stanulla M: NQO1 C609T polymorphism in distinct entities of pediatric hematologic neoplasms. Haematologica 2004; 89:1492-1497.
  
• Brand KM, Klein C, Zündorf I, Dingermann T, Knöss W: Generation and characterisation of monoclonal antibodies to oleanolic acid. Planta Med 2004; 70: 986-992.
  
• Winckler T, Iranfar N, Beck P, Jennes I, Siol O, Baik U, Loomis WF, Dingermann T: CbfA, the C-module DNA-binding factor, plays an essential role in the initiation of Dictyostelium discoideum development. Eukaryot Cell 2004; 3:1349-1358.
  
• Classen B, Csávás M, Borbás A, Dingermann T, Zündorf I: Monoclonal antibodies against an arabinogalactan-protein from pressed juice of Echinacea purpurea. Planta Med 2004; 70: 861-865.
  
• Bursen A, Moritz S, Gaussmann A, Moritz S, Dingermann T, Marschalek R: Interaction of AF4 wild-type and AF4.MLL fusion protein with SIAH proteins: indication for t(4;11) pathobiology? Oncogene 2004; 23: 6237-6249.
  
• Rohmann A, Lochmann D, Weyermann J, Bertling WM, Dingermann T, Zimmer A: Rapid screening method for antisense oligonucleotides against human growth factor receptor p185(erbB-2). Oligonucleotides 2004; 14:1-9.
  
• Szafranski K, Dingermann T, Glöckner G, Winckler T: Template jumping by a LINE reverse transcriptase has created a SINE-like 5S rRNA retropseudogene in Dictyostelium. Mol Genet Genomics 2004; 271: 98-102.
  
• Boehden GS, Restle A, Marschalek R, Stocking C, Wiesmüller L: Recombination at chromosomal sequences involved in leukaemogenic rearrangements is differentially regulated by p53. Carcinogenesis 2004; 25: 1305-1313.