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Klinik für Innere Medizin IHämatologie, Onkologie und Stammzelltransplantation

Tumor immunology and T cell based immunotherapies

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

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. A substantial fraction of patients respond to ICI and responses are frequently durable and even curative. However, by increasing the patient’s endogenous immune response, 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. So far, there are no reliable biomarkers to identify patients that are at high risk of developing irAEs. Therefore, we aim to elucidate the mechanisms of and find novel biomarkers for irAE development, with a focus on microRNAs.

Tamina Rückert

Molekularmedizinerin
PhD Studentin

tamina.rueckert@uniklinik-freiburg.de

Förderung

2019-2022 Mechtild Harf Research Grant (DKMS Foundation for Giving Life)

Auszeichnungen

2018EIRA Mentoring Program for women in science, University of Freiburg
2015 DAG-KBT Research Award (German Working Group for Blood and Marrow Transplantation)
2012-2015SGBM PhD scholarship
2014Barbara Hobom Prize for excellent female scientists, BIOSS, Freiburg
2014ASH Abstract Achievement Award, ASH Annual Meeting, San Francisco, USA
2014Poster Prize, Florey International Postgraduate Research Conference, Adelaide, Australia
2014Scholarship for research visit at the University of Adelaide, Australia
2011Carl Duisberg Scholarship (Bayer fellowship program) for research project in the USA
  • 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.
  • Prof. Dr. A. Schmitt-Gräff (Institut für Klinische Pathologie, Universitätsklinikum Freiburg)
  • Prof. Dr. Robert Zeiser (Klinik für Innere Medizin I, Universitätsklinikum Freiburg)
  • Dr. Dr. Melanie Börries (Institut für Molekulare Medizin und Zellforschung, Freiburg)
  • Dr. P. Apostolova (MPI-IE und Klinik für Innere Medizin I, Universitätsklinikum Freiburg)
  • Prof. Dr. T. Brummer (Institut für Molekulare Medizin und Zellforschung, Freiburg)
  • Prof. Dr. P. Kohl (Universitäts-Herzzentrum Freiburg - Bad Krozingen)
  • Prof. Dr. J. Wehkamp (Universitätsklinikum Tübingen)
  • PD Dr. J. Walz (Universitätsklinikum Tübingen)
  • Dr. Dr. A. Bhatt (Stanford University, USA)
  • Prof. Dr. B. Blazar (University of Minnesota, USA)
Junior group leader

Dr. Natalie Köhler (née Stickel)

Tel.: +49 761 270 71825
E-Mail: natalie.koehler@uniklinik-freiburg.de