Mass cytometry permits deep cellular phenotyping in clinical immunology and basic research, with more than 50 parameters that can be measured simultaneously in a single assay. This is achieved by combining principles of flow cytometry and inductively coupled plasma mass spectrometry (ICP-MS), a technology that has been developed for trace metal analysis.
Using mass cytometry, we perform biomarker discovery studies in several cohorts of patients with different chronic inflammatory diseases such as rheumatoid arthritis, SLE, and inflammatory bowel diseases. We follow the idea that the blood cytome contains important yet covered information about the patient’s condition and response to future therapy. We pursue cytomics to achieve precision medicine in the treatment of chronic inflammation and aim at developing a diagnostic that can be used to select only effective treatments – individually for each patient.
In basic research, we use mass cytometry to capture the diversity of different cell types implicated in chronic inflammatory processes such as T and B lymphocytes, plasma cells and myeloid immune cells. Such diversity relates to e.g. states of cell differentiation and activation, migration and adhesion, apoptosis and survival. Understanding the complexity of cellular systems and provides new insight into the homeostasis and dynamics of immunity, which are of particular interest in cases of specialized lymphocytes bearing protective vs. autoreactive immune memory, and of immune cells that fuel acute inflammation such as monocytes.
To serve these aims at maximum quality, we strive for improving mass cytometry endeavours by developing and improving cell sample barcoding, expanding the measurement capacity by generating new probes and by developing and validating accessory techniques to minimize experimental variations such as cell preservation and antibody cocktail lyophilisation. Implementing these features helps to improve theaccuracy of measurements and the interpretation of highly complex multi-dimensional datasets by downstream computational analyses.
Prof. Holden Maecker, HIMC/ Microbiology & Immunology, Stanford, USA
Dr. Norbert Jakubowski, Dr. Jochen Vogl, BAM, Berlin, Deutschland
Prof. Margitta Worm and PD Dr. Guido Heine, Charité Berlin
Prof. Andreas Krause, Dr. Julia Patermann, Immanual Hospital Berlin-Wannsee
PD Dr. Philipp Engelhard, PD Dr. Adrian Schreiber, Charité Berlin
Prof. Susann Müller, Leipzig, Helmholtz-Zentrum für Umweltforschung
Dr. Uta Kossatz, Univ. Tübingen, Deutschland
Prof. Stefan Schreiber, Univ. Klinik Schleswig-Holstein, Kiel, Deutschland
PD Dr. Thomas Häupl, Dr. Till Sörensen, Dr. Melanie Conrad, PD Dr. Adrian Schreiber, Dr. Angela Ariza de Schellenberger, Charité Berlin
Dr. Desiree Kunkel, BCRT, Berlin, Deutschland
Dr. Christian Dose, Dr. Susanne Krauthäuser, Miltenyi Biotec, Bergisch-Gladbach, Deutschland
Dr. Larissa Müller, Thermo Fisher, Bremen
Ben Pacheco, PhD, Cytodiagnostics, Burlington, ON, Canada
Fluidigm Sciences, South San Francisco, CA, USA
Spherotech Inc., Lake Forest, IL, USA
Baumgart, S., Peddinghaus, A., Schulte-Wrede, U., Mei, H. E. & Grutzkau, A. OMIP-034: Comprehensive immune phenotyping of human peripheral leukocytes by mass cytometry for monitoring immunomodulatory therapies. Cytometry A 91, 34-38, doi:10.1002/cyto.a.22894 (2017).
Schulz, A. R., Stanislawiak, S., Baumgart, S., Grutzkau, A. & Mei, H. E. Silver nanoparticles for the detection of cell surface antigens in mass cytometry. Cytometry A 91, 25-33, doi:10.1002/cyto.a.22904 (2017).
Mei, H. E., Leipold, M. D. & Maecker, H. T. Platinum-conjugated antibodies for application in mass cytometry. Cytometry A, doi:10.1002/cyto.a.22778 (2015).
Mei, H. E., Leipold, M. D., Schulz, A. R., Chester, C. & Maecker, H. T. Barcoding of live human peripheral blood mononuclear cells for multiplexed mass cytometry. J Immunol 194, 2022-2031, doi:10.4049/jimmunol.1402661 (2015).
Sorensen, T., Baumgart, S., Durek, P., Grutzkau, A. & Haupl, T. immunoClust–An automated analysis pipeline for the identification of immunophenotypic signatures in high-dimensional cytometric datasets. Cytometry A 87, 603-615, doi:10.1002/cyto.a.22626 (2015).
The recently developed mass cytometry (CyTOF technology) captures the complexity of cellular systems at unprecedented depth, promising significant contributions in biomedical research and diagnostics. The German Rheumatism Research Center Berlin (DRFZ) initiates the foundation of a nationwide mass cytometry network, GERMANET (GERman MAss cytometry NETwork), that bundles expertise of all German mass cytometry centers, at the DRFZ, the Berlin-Brandenburg Center for Regenerative Therapies (BCRT, Charité Berlin), the Center for Regenerative Therapies of the TU Dresden (CRTD), and the University Clinics Ulm. The complexity of mass cytometry projects represents significant hurdles and risks for individual researchers, which will be minimized by interconnecting and joining forces of German mass cytometry centers along a divide-and-conquer strategy. Aims of this network are to i) boost communication between new and experienced users, technology developers, and data analysis experts, to benefit individual researchers projects, ii) the exploitation of synergies in panel design and technology development arising from the centers complementary research scope, iii) quality assurance of mass cytometric analyses and data, and their reproducibility, and iv) facilitating bioinformatic analyses. This will be achieved by i) intense project supervision in the planning, execution and analysis phase, joint regular workshops and seminars, the installation of the researcher exchange program and mutual technology transfer, ii) the introduction of modular panels and the development of new technologies, iii) establishing joint quality standards and their integration into routines, and their validation in ring-trials, and iv) installing the Bioinformatics Contact Office. Thus, GERMANET facilitates the international competitiveness of German mass cytometry.
Henrik Mei Deutsches Rheuma-Forschungszentrum Berlin (DRFZ)
Désirée Kunkel Berlin-Brandenburger Centrum für Regenerative Therapien, Berlin (BCRT)
Jan Sodenkamp Center for Translational Cancer Research, Munich (TranslaTUM)
Manfred Hönig Universitätsklinikum Ulm
Ezio Bonifacio Center for Regenerative Therapies Dresden (CRTD)
Biomarker und Biosignaturen
Biosensoren für rheumatische Entzündung
Dr.rer. nat. Henrik Mei
Dr. rer. nat. Andreas Grützkau
Dr. Sabine Baumgart
Dr. Axel Ronald Schulz