Systems Immunology and Single Cell Biology

Junior Research Group Systems Immunology and Single Cell Biology

Dr. Felix Hartmann

Multiplexed Ion Beam Imaging (MIBI) for high-dimensional proteomic imaging. a MIBI technology overview. b Exemplary images of human colon FFPE samples imaged by MIBI. Up to 40 antibody-dimensions can be analyzed simultaneously. c High-dimensional imaging data can be used to analyze protein co-expression patterns. d Neural-network (NN) based cell segmentation allows identification of individual cells. Resulting single-cell data can be analyzed with computational approaches to determine cell identities which can be mapped back onto images to determine spatial distribution patterns. Scale bars = 100 um.
© dkfz.de

Progression and clinical outcomes of many human diseases are influenced by cellular interactions in the local tissue microenvironment. We want to understand the spatial organization and cellular regulation of the human immune system and how these processes are influenced by the interplay with the local environment.

To do so, we combine high-dimensional imaging and single-cell methods with advanced computational analysis. We use a novel imaging platform termed MIBI (multiplexed ion beam imaging), which uses metal-conjugated antibodies to enable highly multiplexed (up to 50 dimensions) imaging of cell-specific protein expression and spatial localization directly in clinical (FFPE) tissues. This will be complemented by single-cell analysis via mass cytometry (CyTOF) which enables simultaneously analysis of more than 70 proteomic parameters across millions of individual cells and thus allows us to perform functional assays of human immune cells.

Our research combines:

Systems Immunology. Analysis of the immune system in human tissues via multiplexed imaging. Together with clinicians, we profile samples from clinical trials with a focus on cancer but also inflammation/autoimmunity and cardiovascular disease.

Single-Cell Biology: We develop experimental tools to study novel aspects of cell biology on the single-cell level, e.g. the connection of cellular metabolism and epigenetic remodeling.

Computational tools: In collaboration with computational scientists, we apply novel approaches that utilize the singe-cell and subcellular nature of our multiplexed imaging and single-cell datasets.

Our vision is to make use and further improve these technologies and approaches to reveal novel mechanisms of microenvironmental immune regulation. We hope that this will advance our understanding of the interactions between the immune system and the local tissue structure and thus contribute future improvements immunotherapeutic approaches in cancer and beyond.

Contact

Dr. Felix Hartmann
Systems Immunology and Single Cell Biology (D260)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 3310

Selected Publications

  • Hartmann FJ, Mrdjen D, McCaffrey E, Glass DR, Greenwald NF, Bharadwaj A, Khair Z, Verberk SGS, Baranski A, Baskar R, Graf W, Van Valen D, Van den Bossche J, Angelo M, Bendall SC. Single-cell metabolic profiling of human cytotoxic T cells. Nat Biotechnol. 2021 Feb;39(2):186-197.
  • Hartmann FJ, Bendall SC. Immune monitoring using mass cytometry and related high-dimensional imaging approaches. Nat Rev Rheumatol. 2020 Feb;16(2):87-99
  • Galli E*, Hartmann FJ*, Schreiner B, Ingelfinger F, Arvaniti E, Diebold M, Mrdjen D, van der Meer F, Krieg C, Nimer FA, Sanderson N, Stadelmann C, Khademi M, Piehl F, Claassen M, Derfuss T, Olsson T, Becher B. GM-CSF and CXCR4 define a T helper cell signature in multiple sclerosis. Nat Med. 2019 Aug;25(8):1290-1300 *contributed equally
  • Hartmann FJ, Babdor J, Gherardini PF, Amir ED, Jones K, Sahaf B, Marquez DM, Krutzik P, O'Donnell E, Sigal N, Maecker HT, Meyer E, Spitzer MH, Bendall SC. Comprehensive Immune Monitoring of Clinical Trials to Advance Human Immunotherapy. Cell Rep. 2019 Jul 16;28(3):819-831.e4
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