RG Bruns: Research Group Immunmodulation des Tumormikromilieus

Medicine 5

Head of Department:
Prof. Dr. med. Andreas Mackensen
Team RG Bruns

Dr. Heiko Bruns (PI), Heidi Balzer (MTA), Steffi Moi (MTA), Leonhard Busch (Doctoral student)

Scientific focus

Macrophages are the main component of the tumor microenvironment in the most malignancies. Although macrophages can, in principle, target neoplastic cells and mediate antibody-dependent cytotoxicity, tumor-associated macrophages (TAMs) regularly fail to exert direct cytotoxic functions. However, TAMs are thought to be pro-tumorigenic because they promote angiogenesis and metastasis. The underlying mechanisms responsible for this observation remain unclear. Our research is focused on the functional and molecular analysis of the tumor microenvironment, and identifying and modulating potential therapeutic target structures. Our long-term goal is the specific targeting and modulating of the tumor microenvironment to enhance the effectiveness of immunotherapeutic strategies in malignant lymphomas.

Current projects:

  1. Effector functions of TAMs in malignant lymphomas.
  2. Impact of immunmodulatory  drugs  on the tumor microenviroment.
  3. Transdifferentiation of malignant B-cells into macrophages.

Methods:

  •  Flow cytometry
  • ELISA
  • Quantitative RT-PCR
  • Westernblot
  • Confocal microscopy
  • Chromatin immunoprecipitation
  • Isolation of  microvesicles by ultracentrifugation  
  • Untersuchung von TAMs in verschiedenen Mausmodellen

Collaborations:

intern

Christian Bach, Medizinische Klinik 5
Steffen Backert, Department Biologie
Jacobus Bosch, Medizinische Klinik 5
Maike Büttner, Pathologisches Institut
Udo Gaipl, Strahlenklinik
Markus Hoffmann, Medizinische Klinik 3
Dimitrios Mougiakakos, Medizinische Klinik 5

extern

Fabian Beier, Medizinische Klinik IV, Universitätsklinikum RWTH Aachen
Mario Fabri, Klinik und Poliklinik für Dermatologie, Universitätsklinikum Köln
Thomas Graf, Centre for Genomic Regulation, Barcelona, Spanien
Jan Krönke,  Medizinische Klinik III, Universitätsklinikum Ulm 
Georg Lenz, Medizinische Klinik A, Universitätsklinikum Münster
Jens Nolting, Medizinische Klinik 3, Universitätsklinikum Bonn
Joachim L. Schultze, Life & Medical Sciences Institute (LIMES), Universität Bonn
Christian Schütz, Paul-Ehrlich-Institut, Langen
Steffen Stenger, Medizinische Mikrobiologie, Universitätsklinikum Ulm
Robert Zeiser, Klinik für Innere Medizin I, Hämatologie, Onkologie und Stammzelltransplantation Universitätsklinikum Freiburg

Support and promotion:

  • Erich und Gertrud Roggenbuck Stiftung
  • Johannes und Frieda Marohn-Stiftung
  • Angelika und Helmut Trunk-Stiftung
  • Celgene GmbH
  • MorphoSys AG
  • Therapure Biopharma
  • Wilhelm Sander-Stiftung

Selected Publications:

 Bruns, H., Buttner, M., Fabri, M., Mougiakakos, D., Bittenbring, J. T., Hoffmann, M. H., Beier, F., Pasemann, S.,Jitschin, R., Hofmann, A. D., Neumann, F., Daniel, C., Maurberger, A., Kempkes, B., Amann, K., Mackensen, A. and Gerbitz, A., Vitamin D-dependent induction of cathelicidin in human macrophages results in cytotoxicity against high-grade B cell lymphoma. Sci. Transl. Med. (2015)

 Bruns, H., Bessell, C., Varela, J. C., Haupt, C., Fang, J., Pasemann, S., Mackensen, A., Oelke, M., Schneck, J. P. and Schutz, C., CD47 Enhances In Vivo Functionality of Artificial Antigen-Presenting Cells. Clin. Cancer Res. (2015)

Bruns H, Stegelmann F, Fabri M, Döhner K, van Zandbergen G, Wagner M, Skinner M,. Modlin RL and Stenger S. Abelson Tyrosine Kinase Controls Phagosomal Acidification Required for Killing of Mycobacterium tuberculosis in Human Macrophages. J Immunol. (2012)

Fabri M., S. Stenger, D.-M. Shin, J.-M. Yuk, P. T. Liu, S. Realegeno, H.-M. Lee, S. R. Krutzik, M. Schenk, P. A. Sieling, R. Teles, D. Montoya, S. S. Iyer, Bruns H, D. M. Lewinsohn, B. W. Hollis,M. Hewison, J. S. Adams, A. Steinmeyer, U. Zügel, G. Cheng, E.-K. Jo, B. R. Bloom, R. L. Modlin. Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. Sci. Transl. Med. (2011)

Bruns H, Meinken C, Schauenberg P, Härter G, Kern P, Modlin R, Antoni C, Stenger S. Anti-TNF immunotherapy reduces CD8+T cell mediated antimicrobial activity against Mycobacterium tuberculosis in humans. J. Clin. Invest (2009)

News release:

Mit-Vitamin-D-gegen-Krebs

Vitamin-D-Hilfe-im-Kampf-gegen-Krebs (Interview im Deutschlandfunkt)

Verwandlungskünstler im Fokus der Forschung

Publikationen der Medizin 5

 

 

 
Contact
Dr. rer. nat. Heiko Bruns
DECT: +49 9131 85-43170
e-mail: heiko.bruns@uk-erlangen.de
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Summary