Principal Investigators

Jun. Prof. Dr. Natalie Köhler

Junior Professor

Jun. Prof. Dr. Natalie Köhler

Kontakt

Jun. Prof. Dr. Natalie Köhler
(she/her)

Department of Internal Medicine I, Hematology and Oncology, University Medical Center, Faculty of Medicine)
Center for Translational Cell Research (ZTZ)

T +49 761 270 71828
natalie.koehler(at)uniklinik-freiburg.de

Weitere Informationen

Tumor immunology and T cell based immunotherapies

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potential curative therapy option for patients with hematological malignancies and is based on 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 potential 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.

10 selected publications:

  • Human β-defensin 2 ameliorates acute GVHD by limiting ileal neutrophil infiltration and restraining T cell receptor signaling.
    Rückert T, Andrieux G, Boerries M, Hanke-Müller K, Woessner NM, Doetsch S, Schell C, Aumann K, Kolter J, Schmitt-Graeff A, Schiff M, Braun LM, Haring E, Kissel S, Siranosian BA, Bhatt AS, Nordkild P, Wehkamp J, Jensen BAH, Minguet S, Duyster J, Zeiser R, Köhler N. (2022)
    Sci Transl Med. 21;14(676):eabp9675.
  • MicroRNA-146a regulates immune-related adverse events caused by immune checkpoint inhibitors.
    Marschner D*, Falk M*, Javorniczky NR, Hanke-Müller K, Rawluk J, Schmitt-Graeff A, Simonetta F, Haring E, Dicks S, Ku M, Duquesne S, Aumann K, Rafei-Shamsabadi D, Meiss F, Marschner P, Boerries M, Negrin RS, Duyster J, Zeiser R, Köhler N. (2020)
    JCI Insight. 26;5(6):e132334.
  • The oncogenic fusion protein DNAJB1-PRKACA can be specifically targeted by peptide-based immunotherapy in fibrolamellar hepatocellular carcinoma.
    Bauer J, Köhler N, Maringer Y, Bucher P, Bilich T, Zwick M, Dicks S, Nelde A, Dubbelaar M, Scheid J, Wacker M, Heitmann JS, Schroeder S, Rieth J, Denk M, Richter M, Klein R, Bonzheim I, Luibrand J, Holzer U, Ebinger M, Brecht IB, Bitzer M, Boerries M, Feucht J, Salih HR, Rammensee HG, Hailfinger S, Walz JS. (2022)
    Nat Commun. 27;13(1):6401.
  • Analysis of T cell Repertoire and Transcriptome Identifies Mechanisms of Regulatory T cell (Treg) Suppression of GvHD.
    Lohmeyer JK, Hirai T, Turkoz M, Buhler S, Lopes Ramos T, Köhler N, Baker J, Melotti A, Wagner I, Pradier A, Wang S, Ji X, Becattini S, Villard J, Merkler D, Chalandon Y, Negrin RS, Simonetta F. (2023)
    Blood. 2023 Apr 6;141(14):1755-1767.
  • MicroRNA-146a reduces MHC-II expression via targeting JAK/STAT-signaling in dendritic cells after stem cell transplantation.
    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. (2017)
    Leukemia. 31(12):2732-2741. (* shared first authorship)
  • MiR-146a regulates the TRAF6/TNF-axis in donor T cells during GvHD.
    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 (2014)
    Blood. 16;124(16):2586-95.
  • Glucagon like peptide-2 for Intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans.
    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, Kröger N, Blazar BR, Boerries M, Ayuk F*, Zeiser R* (2020)
    Blood. 17;136(12):1442-1455.
  • MiR-146a controls immune response in the melanoma microenvironment. )
    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. (2019)
    Cancer Research 1;79(1):183-195.
  • The Nlrp3 inflammasome regulates acute graft-versus-host disease.
    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. (2013)
    J Exp Med. 23;210(10):1899-910. (* shared first authorship)
  • The microenvironment differentially impairs passive and active immunotherapy in chronic lymphocytic leukaemia – CXCR4 antagonists as potential adjuvants for monoclonal antibodies.
    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. (2010)
    Br J Haematol. 151(2):167-78.