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Klinik für Innere Medizin IHämatologie, Onkologie und Stammzelltransplantation

Köhler Laboratory

Tumor immunology and T cell based immunotherapies

Scientific focus

The research of our group is focused on tumor immunology and T cell based immunotherapies.

 

Team

Dr. Natalie Köhler

Dr. Natalie Köhler
Junior group leader
Tel.: +49 761 270 71825
natalie.koehler@uniklinik-freiburg.de

Tamina Rückert

Tamina Rückert
PhD student
tamina.rueckert@uniklinik-freiburg.de

Melissa Zwick

Melissa Zwick
PhD student
melissa.zwick@uniklinik-freiburg.de

With the advent of allogeneic hematopoietic cell transplantation (allo-HCT) it became possible for the first time to cure patients with high risk leukemias and lymphomas. The reason for this treatment success is the beneficial graft-versus-leukemia (GvL) effect, in which allogeneic T cells present in the graft recognize and eliminate residual leukemia cells. However, the allogeneic T cells can also attack healthy tissues of the recipient, resulting in graft-versus-host disease (GvHD), a severe and potentially life threatening complication of allo-HCT. Therefore our lab is interested in further analysing the molecular mechanisms of these two effects, in order to find potentially new therapies that target GvHD while sparing the beneficial GVL Effect. For this aim we use classical genetic mouse models and T cell characterization approaches as well as novel NGS-based technologies, including single cell RNA sequencing.

The second focus of our research is the identification of novel targets for immunotherapies in hematological malignancies, in particular key regulators of immune checkpoint molecules. With the development of immune checkpoint inhibitors (ICI), the treatment landscape of numerous cancer entities has been revolutionized. However, to date only a subset of patients responds to ICI therapy and ICI can also induce severe immune-related adverse events (irAEs), which oftentimes require ICI discontinuation and corticosteroid treatment, hence limiting the success of ICI therapy. Therefore, we are studying novel regulators of immune checkpoint molecules and how oncogenic signaling induces immune checkpoint molecule expression and immune escape in the context of hematological malignancies. Furthermore, we aim to elucidate the mechanisms of and find novel biomarkers for irAE development during ICI therapy.

2020 - 2023

Else Kröner-Fresenius-Stiftung (EKFS) Grant

2020 - 2021

Medical Scientist Fellowship (EQUIP Programme, Freiburg)

2019

Grünewald-Zuberbier-Stiftung Grant for research fellowship at Stanford University

2019 - 2022

Mechtild Harf Research Grant (DKMS Foundation for Giving Life)

Internal collaborations

  • Prof. Dr. Dr. Melanie Börries (Insitut für Bioinformatik und System-Medizin)
  • PD Dr. Lena Illert (Klinik für Innere Medizin I)
  • PD Dr. Konrad Aumann (Institut für Klinische Pathologie)
  • Prof. Dr. Robert Zeiser (Klinik für Innere Medizin I)
  • Dr. Dietrich Rueß (Klinik für Allgemein- und Viszeralchirurgie)
  • Prof. Dr. Gerd Walz (Klinik für Innere Medizin IV)
  • PD Dr. Susana Minguet (Institut für Biologie III)
  • Prof. Dr. Tilman Brummer (Institut für Molekulare Medizin und Zellforschung)
  • Prof. Dr. Olaf Groß (Institut für Neuropathologie)
  • Dr. Petya Apostolova (MPI-IE)
  • Dr. Dominic Grün (MPI-IE)
  • Prof. Dr. Peter Kohl (Universitäts-Herzzentrum Freiburg - Bad Krozingen)

External collaborations

  • Dr. Dr. Ami Bhatt (Stanford University, USA)
  • Prof. Dr. Robert Negrin (Stanford University)
  • Prof. Dr. Bruce Blazar (University of Minnesota, USA)
  • Dr. Marcin Kortylewski (City of Hope National Medical Center)
  • PD Dr. Juliane Walz (Universitätsklinikum Tübingen)
  • Dr. Dr. Federico Simonetta (University of Geneva)

  • Norona J, Apostolova P, Schmidt D, Ihlemann R, Reischmann N, Taylor G, Köhler N, de Heer J, Heeg S, Andrieux G, Siranosian BA, Schmitt-Graeff A, Pfeifer D, Catalano A, Frew IJ, Proietti M, Grimbacher B, Bulashevska A, Bhatt AS, Brummer T, Clauditz T, Zabelina T, Kroeger N, Blazar BR, Boerries M, Ayuk F, Zeiser R: Glucagon-like peptide 2 for intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans. Blood. 2020 Sep 17;136(12):1442-1455.
  • Marschner D, Falk M, Hanke-Müller K, Javorniczky NR, Rawluk J, Duquesne S, Schmitt-Graeff A, Haring E, Aumann K, Marschner P, Dicks S, Rafei-Shamsabadi D, Meiss F, Boerries M, Duyster J, Zeiser R, Köhler N: MicroRNA-146a regulates immune-related adverse events caused by immune checkpoint inhibitors. JCI Insight. 2020 Mar 26;5(6):e132334.
  • Köhler N, Zeiser R: Intestinal Microbiota Influence Immune Tolerance post Allogeneic Hematopoietic Cell Transplantation and intestinal GVHD. Front Immunol. 2019 Jan 17;9:3179. 
  • Mastroianni J, Stickel N (Köhler N), Andrlová H, Hanke K, Melchinger W, Duquesne S, Schmidt D, Falk M, Andrieux G, Pfeifer D, Dierbach H, Schmitt-Graeff A, Meiss F, Boerries M, Zeiser R: MiR-146a controls immune response in the melanoma microenvironment. Cancer Res. 2019 Jan 1;79(1):183-195.
  • Stickel N (Köhler N)*, Hanke K*, Marschner D, Prinz G, Köhler M, Melchinger W, Pfeifer D, Schmitt-Graeff A, Brummer T, Heine A, Brossart P, Wolf D, von Bubnoff N, Finke J, Duyster J, Ferrara J, Salzer U, Zeiser R: MicroRNA-146a reduces MHC-II expression via targeting JAK/STAT-signaling in dendritic cells after stem cell transplantation. Leukemia. 2017 Dec;31(12):2732-2741. (* shared first authors)
  • Fontes JA, Barin JG, Talor MV, Stickel N (Köhler N), Schaub J, Rose NR, Ciháková D: Complete Freund’s adjuvant induces experimental autoimmune myocarditis by enhancing IL-6 production during initiation of the immune response. Immun Inflamm Dis. 2017 Jun;5(2):163-176.
  • Köhler M, Röring M, Schorch B, Heilmann K, Stickel N (Köhler N), Fiala GJ, Schmitt LC, Braun S, Ehrenfeld S, Uhl FM, Kaltenbacher T, Weinberg F, Herzog S, Zeiser R, Schamel WW, Jumaa H, Brummer T: Activation loop phosphorylation regulates B-Raf in vivo and transformation by B-Raf mutants. EMBO J. 2016 Jan 18;35(2):143-61.
  • Stickel N (Köhler N), Prinz G, Pfeifer D, Hasselblatt P, Schmitt-Graeff A, Follo M, Thimme R, Finke J, Duyster J, Salzer U, Zeiser R: MiR-146a regulates the TRAF6/TNF-axis in donor T cells during GvHD. Blood. 2014 Oct 16;124(16):2586-95.
  • Stickel N (Köhler N), Zeiser R: The role of microRNAs in immunoregulation after allo-HCT. DMW. 2014 Aug;139(33):1673-8.
  • Barin JG, Baldeviano GC, Talor MV, Wu L, Ong S, Fairweather D, Bedja D, Stickel N (Köhler N), Fontes JA, Cardamone AB, Zheng D, Gabrielson KL, Rose NR, Ciháková D (2013): Fatal eosinophilic myocarditis develops in the absence of IFN-γ and IL-17A. J Immunol. 2013 Oct 15;191(8):4038-47.
  • Jankovic D*, Ganesan J*, Bscheider M*, Stickel N (Köhler N), Weber FC, Guarda G, Follo M, Pfeifer D, Tardivel A, Ludigs K, Bouazzaoui A, Kerl K, Fischer JC, Haas T, Schmitt-Gräff A, Manoharan A, Müller L, Finke J, Martin SF, Gorka O, Peschel C, Ruland J, Idzko M, Duyster J, Holler E, French LE, Poeck H, Contassot E, Zeiser R: The Nlrp3 inflammasome regulates acute graft-versus-host disease. J Exp Med. 2013 Sep 23;210(10):1899-910. (* shared first authors)
  • Buchner M, Brantner P, Stickel N (Köhler N), Prinz G, Burger M, Bär C, Dierks C, Pfeifer D, Ott A, Mertelsmann R, Gribben JG, Veelken H and Zirlik K: The microenvironment differentially impairs passive and active immunotherapy in chronic lymphocytic leukaemia – CXCR4 antagonists as potential adjuvants for monoclonal antibodies. Br J Haematol. 2010 Oct;151(2):167-78.

2020

Selected for participation in the 70th Lindau Nobel Laureate Meeting

2018

EIRA Mentoring Program for women in science, University of Freiburg

2015

ASH Abstract Achievement Award, ASH Annual Meeting, USA

2015

DAG-KBT Research Award, German Working Group for Blood and Marrow Transplantation

2012 - 2015

SGBM PhD scholarship (DFG Excellence Initiative)

2014

Barbara Hobom Prize for excellent female scientists, BIOSS, Freiburg

2014

Poster Award, Florey International Postgraduate Research Conference, Adelaide, Australia

2014

Travel grant for research visit at the University of Adelaide (AC21 program)

2014

ASH Abstract Achievement Award, ASH Annual Meeting, USA

2011

Carl Duisberg Scholarship (Bayer fellowship program) for research stay in the USA