Department of Medicine
Clinical Collaboration Unit Translational Immunology

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Address: Otfried-Müller-Str. 10
72076 Tübingen

Administration Office

frontend.sr-only_#{element.icon}: +49 7071 29-83275

frontend.sr-only_#{element.icon}: +49 7071 29-4391

frontend.sr-only_#{element.icon}: ira.breitkreuz@med.uni-tuebingen.de

AG Märklin

Scientific focus

The issue how tumors evade the immune system and why immune cells fail to control tumor progression are questions which fascinate scientific researchers for many years. The Ca²⁺/NFAT signaling pathway, which is the focus of our scientific interest, was identified to play an important role in tumor cell biology acting as tumor suppressor as well as oncogene in a large variety of tumor entities. Furthermore, it tightly regulates activation and proliferation of immune cells, thereby also modulating recognition of tumor cells.

Our work is aimed to elucidate the role of NFAT transcription factors in the context of the

molecular mechanisms regulating NK cell reactivity
immunosurveillance of CLL and resistance to NK cell mediated killing
modulation of leukemic cell recognition by immune cells

We characterize host-tumor interaction with a special focus on activation and antibody-dependent-cellular-cytotoxicity (ADCC) of NK cells. To improve the basic knowledge of NK cell immunosurveillance in CLL, we analyze various immunoregulatory molecules in immune and leukemic cells including the NKG2D/NKG2D ligand molecule system, various members of the TNF/TNFR family and immune checkpoint molecules like PD-1/PD-1L and CTLA-4. Furthermore, we investigate the influence of NFAT expression on the expression of these molecules to develop new therapeutic approaches to enhance tumor cell killing by immune cells.

Contact

frontend.sr-only_#{element.contextual_1.children.icon}: PD Dr. rer. nat. Melanie Märklin Research Group Leader

More about the person

Laboratory

frontend.sr-only_#{element.contextual_1.children.icon}: +49 07071 29-82804
+49 07071 29-82838

Team

Awards and prizes

Young Investigator travel stipend, XVI International Workshop on Chronic Lymphocytic Leukemia, Sydney (09/2015)
Best translation research abstract, Annual meeting of the DGHO, Hamburg (10/2014)
Abstract Achievement Award, Annual Meeting of the American Society of Hematology, Orlando (12/2015)
Abstract Achievement Award, Annual Meeting of the American Society of Hematology, San Francisco (12/2014)
Abstract Award, ASH Meeting on Lymphoma Biology, Colorado Springs (09/2014)
Travel stipend, Meeting on Signal Transduction, Weimar (11/2014)
Abstract Achievement Award, Annual Meeting of the American Society of Hematology, New Orleans (12/2013)
Travel stipend, Meeting on Signal Transduction, Weimar (11/2013)
Abstract Achievement Award, Annual Meeting of the American Society of Hematology, Atlanta (12/2012)
Travel stipend, Meeting on Signal Transduction, Weimar (11/2012)
Poster Award, Annual meeting of the DGHO, Stuttgart (09/2012)
Abstract Achievement Award, Annual Meeting of the American Society of Hematology, San Diego (12/2011)

Selected publications

Märklin M, Hagelstein I, Koerner SP, Rothfelder K, Pfluegler MS, Schumacher A, Grosse-Hovest L, Jung G, Salih HR. Bispecific NKG2D-CD3 and NKG2D-CD16 fusion proteins for induction of NK and T cell reactivity against acute myeloid leukemia. J Immunother Cancer. 2019 May 29;7(1):143.
Müller DJ, Wirths S, Fuchs AR, Märklin M, Heitmann JS, Sturm M, Haap M, Kirschniak A, Sasaki Y, Kanz L, Kopp HG, Müller MR. Loss of NFAT2 expression results in the acceleration of clonal evolution in chronic lymphocytic leukemia. J Leukoc Biol. 2019 Mar;105(3):531-538.
Märklin M, Heitmann JS, Fuchs AR, Truckenmüller FM, Gutknecht M, Bugl S, Saur SJ, Lazarus J, Kohlhofer U, Quintanilla-Martinez L, Rammensee HG, Salih HR, Kopp HG, Haap M, Kirschniak A, Kanz L, Rao A, Wirths S, Müller MR. NFAT2 is a critical regulator of the anergic phenotype in chronic lymphocytic leukaemia. Nat Commun. 2017 Oct 2;8(1):755.