Priv.-Doz. Dr. rer. nat. Frank John Patrick Kühn

Floor 6, Corridor D, Room 23 

Phone: +49 241 80-88803
Fax: +49 241 80-82434
fkuehnukaachende

Academic carreer

1985 – 1992
Diploma Biology at the Ruprecht-Karls-University Heidelberg. With focus on biochemisty, genetics, microbiology and chemistry

1992 – 1995
Ph D. (Dr. rer. nat.) at the Ruprecht-Karls-University Heidelberg, Institute of Virology at the German Cancer Research Center, Heidelberg.
Doctoral Thesis: Mutation and functional analysis of the 3’-5’-exonuclease domain of Herpes Simplex-Virus Type 1 DNA-Polymerase

1996 – 2001
Postdoc at the Institute of Physiology, University Zürich-Irchel, Switzerland in the group of Prof. Dr. med. N.G. Greeff

since Aug. 2001
Postdoc at the Institute of Physiology, RWTH Aachen in the group of Prof. Dr. med. A. Lückhoff

01/2006 – 12/2011
Project leader German Research Foundation (DFG): Molecular charakterisization of the gating mechanism of the cation channels TRPM2 und TRPM8. (KU2271/1-1)

12/2008
Venia legendi (Physiology) Medical Faculty, RWTH-Aachen

01/2015 – 12/2017
Project leader German Research Foundation (DFG): Functional analysis of an evolutionary ancestor of the TRPM subfamily from the sea anemone Nematostella vectensis in vitro and in vivo (KU2271/4-1).

01/2018 – 12/2020
Project leader German Research Foundation (DFG): Functional analysis of an evolutionary ancestor of the TRPM subfamily from the sea anemone Nematostella vectensis in vitro and in vivo (KU2271/4-2).

01/2021 – 12/2023
Project leader in the DFG project: Functional analysis of an evolutionary precursor of the CPMR subfamily from Nematostella vectensis in vitro and in vivo. (KU2271/4-3).

Research Areas

Institute of Physiology, University Zürich-Irchel, Switzerland:

  • Functional characterization of voltage sensor S4D4 in the voltage-dependent sodium channel rNav1.2. Recording of gating currents in Xenopus oocytes using a modified Two Electrode Voltage Clamp (TEVC) device.
  • Funktional characterization of the bovine sodium channel bNav1.5, a cardiac sodium channel variant, which is insensitive to the inactivation blocker DPI 201-206 (piperazinyl indol derivative)

Institute of Physiologie, RWTH Aachen, Germany:

  • Molecular characterization of the gating mechanisms of the cation channels TRPM2 and TRPM8 by functional analysis of channel chimeras. Whole-cell patch-clamp measurements and Ca-imaging experiments, Single-channel recordings.
  • Detailed analysis of the structure-function relationship of splice variants of TRPM2.
  • Test of newly developed substances (derivatives of menthol) regarding their effects on the temperature sensor TRPM8. Inhibitory Effects of icilin.
  • Study of the mechanosensitivity of hTRPA1 by fluid flow. Generation of channel chimeras of hTRPA1 and xlTRPN1.
  • Functional characterization of a TRPM ortholog of the sea anemone Nematostella vectensis heterologously expressed in HEK-293 cells. Discovery of a novel ADPR-dependent gating mechanism of nvTRPM2. Special effects of the calcium channel modulator 2-APB on nvTRPM2 (stimulation of activation, inhibition of inactivation) mediated by the channel pore. Characterization of the functional impact of the S1-S2 linker of nvTRPM2 on channel gating with special focus on the outer pore region.
  • Comparative functional analysis of the TRPM channel of Nematostella vectensis and mTRPM3.

Publications

(*corresponding author)

  1. Frank J.P. Kühn and Charles W. Knopf* (1996). Herpes simplex virus type 1 DNA polymerase. Mutational analysis of the 3’-5’ exonuclease domain. J. Biol. Chem. 271:29245-54.
  2. Cornelia Franz, Frank J.P. Kühn, and Charles W. Knopf* (1999). DNA and protein interactions of the small subunit of herpes simplex type 1 DNA polymerase. Virology 253:55-64.
  3. Uwe Schreiner, Ursula Hansen, Frank J.P. Kühn, and Charles W. Knopf* (1999). A novel protein tag from herpes simplex virus type 1 DNA polymerase. Intervirology 42:17- 21.
  4. Frank J.P. Kühn and Nikolaus G. Greeff* (1999). Movement of voltage sensor S4 in domain 4 is tightly coupled to sodium channel fast inactivation and gating charge immobilization. J.Gen. Physiol. 114:167-83.
  5. Nikolaus G. Greeff* and Frank J.P. Kühn (2000). Sodium influx and variable ratio of permeability to gating charge of rBIIA sodium channels in Xenopus oocytes. Biophys. J. 79:2434-53.
  6. Frank J.P. Kühn* and Nikolaus G. Greeff (2002). Mutation D384N alters recovery of the immobilized gating charge in rat brain II A sodium channels. J. Membr. Biol. 185:145-155. 
  7. Helena Denac, Meike Mevissen*, Frank J.P. Kühn, Cornelia Kühn, Christophe T. Guionaud, Günther Scholtysik and Nikolaus G. Greeff (2002). Molecular cloning and functional characterization of a unique mammalian cardiac Na(v) channel isoform with low sensitivity to the synthetic inactivation inhibitor SDZ 211-939. J Pharmacol. Exp. Ther. 303:89-98.
  8. Frank J.P. Kühn and Nikolaus G. Greeff* (2003). Gating properties of a sodium channel with three arginines substituted by histidines in the central part of voltage sensor S4D4. J. Membr. Biol. 193:23-34.
  9. Frank J.P. Kühn and Andreas Lückhoff* (2004). Sites of the NUDT9-H domain critical for ADP-ribose activation of the cation channel TRPM2. J. Biol. Chem. 279:46431-37.
  10. Inka Heiner, Natasha Radukina, Jörg Eisfeld, Frank J.P. Kühn and Andreas Lückhoff* (2005). Regulation of TRPM2 channels in neutrophil granulocytes by ADP-ribose: a promising pharmacological target. Naunyn Schmiedebergs Arch. Pharmacol. 371:325-33 (invited Review).
  11. Frank J.P. Kühn, Inka Heiner and Andreas Lückhoff* (2005). TRPM2: a calcium influx pathway regulated by oxidative stress and the novel second messenger ADP-ribose. Pflügers Arch. 451:212-19 (invited Review).
  12. Frank J.P. Kühn*, Gabriel Knop and Andreas Lückhoff (2007). The transmembrane segment S6 determines cation versus anion selectivity of TRPM2 and TRPM8. J. Biol. Chem. 282:27598-609. 
  13. Frank J.P. Kühn*, Cornelia Kühn, Mustafa Naziroglu and Andreas Lückhoff (2009). Role of an N-terminal splice segment in the activation of the cation channel TRPM2 by ADP-ribose and hydrogen peroxide. Neurochem. Res. 34:227-33.
  14. Muhammad R. Bari, Sanian Akbar, Mohamed Eweida, Frank J.P. Kühn, Amanda J. Gustafsson, Andreas Lückhoff and Md. Shahidul Islam* (2009). H2O2-induced Ca2+ influx and its inhibition by N-(p-amylcinnamoyl) anthranilic acid in the β-cells involvement of TRPM2 channels. J Cell Mol Med. 13:3260-67.
  15. Frank J.P. Kühn*, Cornelia Kühn and Andreas Lückhoff (2009). Inhibition of TRPM8 by icilin distinct from desensitization induced by menthol and menthol derivatives. J. Biol. Chem. 284:4102-11.
  16. Frank J.P. Kühn*, Katja Witschas, Cornelia Kühn and Andreas Lückhoff (2010). Contribution of the S5-Pore-S6 Domain to the gating characteristics of the cation channels TRPM2 and TRPM8. J. Biol. Chem. 285:26806-814.
  17. Mathis Winking, Daniel C. Hoffmann, Cornelia Kühn, Ralf-Dieter-Hilgers, Andreas Lückhoff and Frank J.P. Kühn* (2012). Importance of a conserved sequence motif in transmembrane segment S3 for the gating of human TRPM8 and TRPM2. PLoS One 7: e49877.
  18. Frank J.P. Kühn*, Mathis Winking, Cornelia Kühn, Daniel C. Hoffmann and Andreas Lückhoff (2013). Surface expression and channel function of TRPM8 are cooperatively controlled by transmembrane segments S3 and S4. Pflügers Arch. 465:1599-1610.
  19. Frank J.P. Kühn*, Cornelia Kühn and Andreas Lückhoff (2015). Functional Characterisation of a TRPM2 orthologue from the sea anemone Nematostella vectensis in human cells. Sci Rep. 5:8032.
  20. Frank J.P. Kühn*, Cornelia Kühn, Mathis Winking, Daniel C. Hoffmann and Andreas Lückhoff (2016). ADP-ribose activates the TRPM2 channel from the sea anemone Nematostella vectensis independently of the NUDT9H domain. PLoS One 11: e0158060.
  21. Frank J.P. Kühn*, Mathis Winking, Cornelia Kühn, Daniel C. Hoffmann and Andreas Lückhoff (2017). Modulation of activation and inactivation by Ca2+ and 2-APB in the pore of an archetypal TRPM channel from Nematostella vectensis. Sci Rep. 7:7245.
  22. Frank J.P. Kühn*, Cornelia Kühn and Andreas Lückhoff (2017). Different principles of ADP-ribose-mediated activation and opposite roles of the NUDT9 homology domain in the TRPM2 orthologs of man and sea anemone. Front. Physiol. 8:879. (invited Review).
  23. Frank J.P. Kühn* (2017). New insights into the interaction between ADP-ribose and human TRPM2 channel. Biotarget 1:14 (invited Editorial).
  24. Frank J.P. Kühn*, Joanna M. Watt Barry V.L. Potter, Andreas Lückhoff (2019). Different substrate specificities of the two ADPR binding sites in TRPM2 channels of Nematostella vectensis and the role of IDPR. Sci Rep. 2019 Mar 21: 9(1):4985. doi:10.1038/s41598-019-41531-4. PMD: 308
  25. Kühn, F.J.P. Ehrlich, W. Barth, D. Kühn, C. Lückhoff, A.
    Functional importance of NUDT9H domain and N-terminal ADPR-binding pocket in two species variants of vertebrate TRPM2 channels.
    Sci Rep 9, 19224 (2019)
  26. Frank J.P. Kühn Structure-Function Relationship of TRPM2: Recent Advances, Contradictions, and Open Questions. Int J Mol Sci. 4:E6481 (2020).