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Friedrich Koch-Nolte

Name of the laboratory

Laboratory of Molecular Immunology
Institute of Immunology
University Medical Center Hamburg-Eppendorf
Martinistr. 42
20246 Hamburg, Germany
xx49-40-741053612

Members of the laboratory

Members: Laboratory of Molecular Immunology
Unit Leader
Friedrich Koch-Nolte nolte@uke.de
Research Fellows
Stephan Menzel s.menzel@uke.de
Nicole Schwarz n.schwarz@uke.de
Thomas Eden t.eden@uke.de
Anna Eichhoff a.eichhoff@uke.de
Mirjam Loew m.loew@uke.de
Technicians
Fabienne Seyfried f.seyfried@uke.de
Gudrun Dubberke gdubberk@uke.de
Birte Albrecht b.albrecht@uke.de
Ph.D. Students
Carolina Pinto c.pinto@uke.de
Thomas Eden t.eden@uke.de
Anna Eichhoff a.eichhoff@uke.de
Intissar Chachbani i.chachbani@uke.de
Tobias Schaefer to.schaefer@uke.de
Julia Hambach j.hambach@uke.de

Research activities

The focus of our laboratory is on the molecular characterization of lymphocyte membrane proteins, in particular receptors and enzymes involved in signaling by extracellular nucleotides. We generate monoclonal antibodies and nanobodies - single domain antibodies derived from camelid heavy chain antibodies - as new research and therapeutic tools. We are interested in ADP-ribosylation as a pathogenic mechanism of bacterial toxins and as a reversible posttranslational modification regulating protein functions. Using genetic immunization and antibody engineering, we strive to develop new tools for combating infections and for treating diseases of the immune system. Many of our monoclonal and recombinant antibodies are commercialized via MediGate GmbH, a 100% subsidy of the University Medical Center Hamburg-Eppendorf.

Techniques available

  • Monoclonal antibody production in rats and mice
  • Polyclonal antibody production
  • Genetic immunization
  • Nanobody production from llamas and dromedaries
  • Recombinant antibody production in HEK cells
  • Cloning techniques
  • Antibody characterization and conjugation
  • Mycoplasma testing
  • Flow cytometry, ELISA, immunofluorescence microscopy, etc.

Publications (2020-present)

  • The ABCD database: a repository for chemically defined antibodies. Lima WC, Gasteiger E, Marcatili P, Duek P, Bairoch A, Cosson P. Nucleic Acids Res. 2019 Aug 14. pii: gkz714. doi: 10.1093/nar/gkz714. [Epub ahead of print] PMID:31410491
  • Eden T, Menzel S, Wesolowski J, Bergmann P, Nissen M, Dubberke G, Seyfried F, Albrecht B, Haag F, Koch-Nolte F. (2018) A cDNA Immunization Strategy to Generate Nanobodies against Membrane Proteins in Native Conformation. Front Immunol. 8:1989.
  • Exploiting Nanobodies' Singular Traits. Ingram JR, Schmidt FI, Ploegh HL. Annu Rev Immunol. 2018 Apr 26;36:695-715. doi: 10.1146/annurev-immunol-042617-053327. PMID: 29490163
  • Fumey W, Koenigsdorf J, Kunick V, Menzel S, Schütze K, Unger M, Schriewer L, Haag F, Adam G, Oberle A, Binder M, Fliegert R, Guse A, Zhao YJ, Cheung Lee H, Malavasi F, Goldbaum F, van Hegelsom R, Stortelers C, Bannas P, Koch-Nolte F. (2017) Nanobodies effectively modulate the enzymatic activity of CD38 and allow specific imaging of CD38+ tumors in mouse models in vivo. Sci Rep. 7:14289.
  • Koch K, Kalusche S, Torres JL, Stanfield RL, Danquah W, Khazanehdari K, von Briesen H, Geertsma ER, Wilson IA, Wernery U, Koch-Nolte F, Ward AB, Dietrich U. (2017) Selection of nanobodies with broad neutralizing potential against primary HIV-1 strains using soluble subtype C gp140 envelope trimers. Sci Rep. 7:8390.
  • Oberle A, Brandt A, Alawi M, Langebrake C, Janjetovic S, Wolschke C, Schütze K, Bannas P, Kröger N, Koch-Nolte F, Bokemeyer C, Binder M. (2017) Long-term CD38 saturation by daratumumab interferes with diagnostic myeloma cell detection. Haematologica. 102:e368-e370.
  • Danquah W, Meyer-Schwesinger C, Rissiek B, Pinto C, Serracant-Prat A, Amadi M, Iacenda D, Knop JH, Hammel A, Bergmann P, Schwarz N, Assunção J, Rotthier W, Haag F, Tolosa E, Bannas P, Boué-Grabot E, Magnus T, Laeremans T, Stortelers C, Koch-Nolte F. (2016) Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation. Sci Transl Med. 8:366ra162.
  • Li T, Qi S, Unger M, Hou YN, Deng QW, Liu J, Lam CM, Wang XW, Xin D, Zhang P, Koch-Nolte F, Hao Q, Zhang H, Lee HC, Zhao YJ. (2016) Immuno-targeting the multifunctional CD38 using nanobody. Sci Rep. 6:27055.
  • Tomas NM, Hoxha E, Reinicke AT, Fester L, Helmchen U, Gerth J, Bachmann F, Budde K, Koch-Nolte F, Zahner G, Rune G, Lambeau G, Meyer-Schwesinger C, Stahl RA. (2016) Autoantibodies against thrombospondin type 1 domain-containing 7A induce membranous nephropathy. J Clin Invest. 126:2519-32.
  • Unger M, Eichhoff AM, Schumacher L, Strysio M, Menzel S, Schwan C, Alzogaray V, Zylberman V, Seman M, Brandner J, Rohde H, Zhu K, Haag F, Mittrücker HW, Goldbaum F, Aktories K, Koch-Nolte F. (2015) Selection of Nanobodies that Block the Enzymatic and Cytotoxic Activities of the Binary Clostridium Difficile Toxin CDT. Sci Rep. 5:7850.
  • Menzel S, Rissiek B, Bannas P, Jakoby T, Miksiewicz M, Schwarz N, Nissen M, Haag F, Tholey A, Koch-Nolte F. Nucleotide-Induced Membrane-Proximal Proteolysis Controls the Substrate Specificity of T Cell Ecto-ADP-Ribosyltransferase ARTC2.2. J Immunol. 2015 Sep 1;195(5):2057-66. PMID: 26209623
  • Teege S, Hann A, Miksiewicz M, MacMillan C, Rissiek B, Buck F, Menzel S, Nissen M, Bannas P, Haag F, Boyer O, Seman M, Adriouch S, Koch-Nolte F. Tuning IL-2 signaling by ADP-ribosylation of CD25. Sci Rep. 2015 Mar 10;5:8959. PMID: 25753532
  • Bannas P, Lenz A, Kunick V, Well L, Fumey W, Rissiek B, Haag F, Schmid J, Schütze K, Eichhoff A, Trepel M, Adam G, Ittrich H, Koch-Nolte F. Molecular imaging of tumors with nanobodies and antibodies: Timing and dosage are crucial factors for improved in vivo detection. Contrast Media Mol Imaging. 2015 Sep-Oct;10(5):367-78. PMID: 25925493
  • Bannas P, Lenz A, Kunick V, Fumey W, Rissiek B, Schmid J, Haag F, Leingärtner A, Trepel M, Adam G, Koch-Nolte F. Validation of nanobody and antibody based in vivo tumor xenograft NIRF-imaging experiments in mice using ex vivo flow cytometry and microscopy. J Vis Exp. 2015 Apr 6;(98):e52462. PMID: 25867711
  • Rissiek B, Danquah W, Haag F, Koch-Nolte F. (2014) Technical Advance: A new cell preparation strategy that greatly improves the yield of vital and functional Tregs and NKT cells. J Leukoc Biol. 95:543-9
  • Bannas P, Well L, Lenz A, Rissiek B, Haag F, Schmid J, Hochgräfe K, Trepel M, Adam G, Ittrich H, Koch-Nolte F. (2014) In vivo near-infrared fluorescence targeting of T cells: comparison of nanobodies and conventional monoclonal antibodies. Contrast Media Mol. Imaging. 9:135-42.
  • Schwarz N, Drouot L, Nicke A, Fliegert R, Boyer O, Guse AH, Haag F, Adriouch S, Koch-Nolte F. (2012) Alternative splicing of the N-terminal cytosolic and transmembrane domains of P2X7 controls gating of the ion channel by ADP-ribosylation. PLoS One. 7:e41269.
  • Alzogaray V, Danquah W, Aguirre A, Urrutia M, Berguer P, García Véscovi E, Haag F, Koch-Nolte F, Goldbaum FA. (2011) Single-domain llama antibodies as specific intracellular inhibitors of SpvB, the actin ADP-ribosylating toxin of Salmonella typhimurium. FASEB J 25:526-34
  • Juarez K, Dubberke G, Lugo P, Koch-Nolte F, Buck F, Haag F, Licea A. (2011) Monoclonal antibodies for the identification and purification of vNAR domains and IgNAR immunoglobulins from the horn shark Heterodontus francisci. Hybridoma (Larchmt). 30:323-9.
  • Hubert S, Rissiek B, Klages K, Huehn J, Sparwasser T, Haag F, Koch-Nolte F, Boyer O, Seman M, Adriouch S. (2010) Extracellular NAD+ shapes the Foxp3+ regulatory T cell compartment through the ART2-P2X7 pathway. J Exp Med. 207:2561-2568.
  • Scheuplein F, Rissiek B, Driver JP, Chen YG, Koch-Nolte F, Serreze DV. (2010) A recombinant heavy chain antibody approach blocks ART2 mediated deletion of an iNKT cell population that upon activation inhibits autoimmune diabetes. J Autoimmun. 34:145-54.
  • Adriouch S, Bannas P, Schwarz N, Fliegert R, Guse AH, Seman M, Haag F, Koch-Nolte F. (2008) ADP-ribosylation at R125 gates the P2X7 ion channel by presenting a covalent ligand to its nucleotide binding site. FASEB J. 22:861-869.
  • Koch-Nolte F, Reyelt R, Schössow B, Schwarz N, Scheuplein F, Rothenburg S, Haag F, Alzogaray V, Cauerhff A, Goldbaum F. (2007) Single domain antibodies from llama effectively and specifically block T cell ecto-ADP-ribosyltransferase ART2.2 in vivo. FASEB J. 21:3490-3498.
  • Möller S, Jung C, Adriouch S, Dubberke G, Seyfried F, Seman M, Haag F, Koch-Nolte F. (2007) Monitoring the expression of purinoceptors and nucleotide-metabolizing ecto-enzymes with antibodies directed against proteins in native conformation. Purinergic Signal. 3:359-66.

Reviews

  • Stortelers C, Pinto-Espinoza C, Van Hoorick D, Koch-Nolte F. (2018) Modulating ion channel function with antibodies and nanobodies. Curr Opin Immunol. 52:18-26.
  • Bannas P, Hambach J, Koch-Nolte F. (2017) Nanobodies and nanobody-based human heavy chain antibodies as antitumor therapeutics. Front Immunol. 8:1603.
  • Rissiek B, Koch-Nolte F, Magnus T. (2014) Nanobodies as modulators of inflammation: potential applications for acute brain injury. Front Cell Neurosci. 8:344.
  • Menzel S, Rissiek B, Haag F, Goldbaum F, Koch-Nolte F. (2013) The art of blocking ARTs: Nanobodies as experimental and therapeutic tools to block mammalian and toxin ADP-ribosyltransferases. FEBS J. 280:3543-50.
  • Wesolowski J, Alzogaray V, Reyelt J, Unger M, Juarez K, Urrutia M, Cauerhff A, Danquah W, Rissiek B, Scheuplein F, Schwarz N, Adriouch S, Boyer O, Seman M, Licea A, Serreze DV, Goldbaum FA, Haag F, Koch-Nolte F (2009) Single domain antibodies: promising experimental and therapeutic tools in infection and immunity. (review) Med Microbiol Immunol 198:157-74.
  • Koch-Nolte F, Haag F, Guse AH, Lund F, Ziegler M. (2009) Emerging roles of NAD+ and its metabolites in cell signaling. Sci Signal. 10:mr1.
  • Koch-Nolte F, Kernstock S, Mueller-Dieckmann C, Weiss MS, Haag F. (2008) Mammalian ADP-ribosyltransferases and ADP-ribosylhydrolases.  Front Biosci. 2008 May 1;13:6716-29.