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Regine von Ramin Lab Molecular Rheumatology

In search of disease-relevant gene regulation patterns

Introduction
Members
Cooperation Partners
Selected Publications

Through the generous bequest from Mrs. Regine von Ramin and further financing by the Berlin senate-administration WiFoku, the Regine-von-Ramin Laboratory for Molecular Rheumatology (RvR-Laboratory) was founded in December of 2004 and is jointly used by research groups of the DRFZ and liaison groups of the Charité for the purposes of genome-wide gene expression analysis, particularly on the level of single-cells (10X Genomics based technology) . Both chip-based Affymetrix® technology and Next-Generation Sequencing Technology (NGS) from Illumina® and PacBio are used.

The RvR-Laboratory contains an Affymetrix-station, which is equipped with the the Scanner 3000 7G and the Fluidics FS450. For the purposes of RNA-sample quality control, a Bioanalyzer (Agilent) and Nanodrop ND-2000 spectral photometer are available in addition to standard instruments. Additionally, the aHybTM-Hybridisation station (Milenyi Biotec) allows for processing of array formats that are spotted on slides, and thereby processes like a miRNA expression profiling using the miRXplore Array (Miltenyi Biotec).

An ideal supplement to this facility is a Laser Capture Microdissection machine (LCM) from Fa. Arcturus, which allows a cutting out of morphologically and immune-histologically characterized tissue samples for molecular analysis without enzymatically digesting them. Both systems are primarily used for molecular analysis of cells at the level of their DNA, RNA and proteins. Through the integration of LCM-technology in the RvR-Laboratory, it is possible to perform global gene expression analysis on tissue samples that are morphologically and immuno-histologically identifiable.

The cooperation between the DRFZ and the Charité spin-off company “BioRetis”, allowed the establishment of a comprehensive mouse- and disease-relevant human transcriptome database. These datasets are freely available for analysis purposes (www.bioretis.com).

Next Generation Sequencing (NGS) technology was established for even more in-depth analyses, which makes it possible not only to analyse known gene sequences, but also the entire transcriptome including non-coding regions and so-called microRNAs, which consist of only very short gene sequences (usually 21 to 23 nucleotides) and above all have gene regulatory tasks. Furthermore, the NGS technology enables the generation of immune receptor repertoires of T- and B-lymphocytes by targeted sequencing, the determination of the microbiome by 16S sequencing.

Keywords
Next-Generation-Sequencing
Transcriptome Analyses
Gene signatures
Genechip-Analyses
Single Cell Sequencing
Mikrobiome Analyses

Immune Monitoring || Regine von Ramin Lab Molecular Rheumatology Dr. rer. nat. Andreas Grützkau Phone +49 (0)30 28460-690 gruetzkau@drfz.de more
Therapeutic Gene Regulation || Regine von Ramin Lab Molecular Rheumatology || BCRT/DRFZ Single-Cell Laboratory for Advanced Cellular Therapies Dr. Mir-Farzin Mashreghi Phone +49 (0)30 28460-752 mashreghi@drfz.de more
Group Leader
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Group leader
Dr. rer. nat. Andreas Grützkau
PD Dr. med. Thomas Häupl
Dr. rer. nat. Mir-Farzin Mashreghi

Technical management
Dr. Gitta Heinz
Dipl. Biotech. Katrin Lehmann

Technical assistance
Heike Hirseland

Group Leader
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  • Dr. rer. nat. S Fillatreau, INEM – Paris
  • Dr. rer. nat. K Tokoyoda, DRFZ – Berlin
  • PD Dr. U. Syrbe, CBF – Charité
  • Dr. D. Poddubnyy, CBF – Charité
  • Dr. rer. nat. A Thiel, BCRT – Charité
  • Dr. rer. nat. F Melchers, DRFZ – Berlin
  • Dr. F Apparailly, INSERM, Montpellier, Frankreich
  • Prof. Dr. A. Diefenbach, DRFZ/Charité
  • Prof. Dr. M. Mall, Charité
  • PD Dr. T. Kallinich, DRFZ/Charité
  • Prof. Dr. B. Opitz, Charité
  • Prof. Dr. W. Kübler, Charité
  • Prof. Dr. H-D Volk, BCRT/Charité
  • Prof. Dr. P. Reinke, BCRT/Charité
  • Prof. Dr. K. Budde, Charité
  • Prof. Dr. A. Scheffold, Universität Kiel
Group Leader
Continue to Selected Publications
  • Beller A, Kruglov A, Durek P, von Goetze V, Werner K, Heinz GA, Ninnemann J, Lehmann K, Maier R, Hoffmann U, Riedel R, Heiking K, Zimmermann J, Siegmund B, Mashreghi MF, Radbruch A, Chang HD. Specific microbiota enhances intestinal IgA levels by inducing TGF-β in T follicular helper cells of Peyer’s patches in mice. Eur J Immunol. 2020 Feb 17. doi:10.1002/eji.201948474.
  • Tizian C, Lahmann A, Hölsken O, Cosovanu C, Kofoed-Branzk M, Heinrich F, Mashreghi MF, Kruglov A, Diefenbach A, Neumann C. c-Maf restrains T-bet-driven programming of CCR6-negative group 3 innate lymphoid cells. Elife. 2020 Feb 10;9. pii: e52549. doi: 10.7554/eLife.52549.
  • Addo RK, Heinrich F, Heinz GA, Schulz D, Sercan-Alp Ö, Lehmann K, Tran CL, Bardua M, Matz M, Löhning M, Hauser AE, Kruglov A, Chang HD, Durek P, Radbruch A, Mashreghi MF. Single-cell transcriptomes of murine bone marrow stromal cells reveal niche-associated heterogeneity. Eur J Immunol. 2019 Sep;49(9):1372-1379. doi: 10.1002/eji.201848053.
  • Lahmann A, Kuhrau J, Fuhrmann F, Heinrich F, Bauer L, Durek P, Mashreghi MF, Hutloff A. Bach2 Controls T Follicular Helper Cells by Direct Repression of Bcl-6. J Immunol. 2019 Apr 15;202(8):2229-2239. doi: 10.4049/jimmunol.1801400.
  • Neumann C, Blume J, Roy U, Teh PP, Vasanthakumar A, Beller A, Liao Y, Heinrich F, Arenzana TL, Hackney JA, Eidenschenk C, Gálvez EJC, Stehle C, Heinz GA, Maschmeyer P, Sidwell T, Hu Y, Amsen D, Romagnani C, Chang HD, Kruglov A, Mashreghi MF, Shi W, Strowig T, Rutz S, Kallies A, Scheffold A. c-Maf-dependent T(reg) cell control of intestinal T(H)17 cells and IgA establishes host-microbiota homeostasis. Nat Immunol. 2019 Apr;20(4):471-481. doi:10.1038/s41590-019-0316-2.
  • Siracusa F, Durek P, McGrath MA, Sercan-Alp Ö, Rao A, Du W, Cendón C, Chang HD, Heinz GA, Mashreghi MF, Radbruch A, Dong J. CD69(+) memory T lymphocytes of the bone marrow and spleen express the signature transcripts of tissue-resident memory T lymphocytes. Eur J Immunol. 2019 Jun;49(6):966-968. doi:10.1002/eji.201847982. Epub 2019 Jan 30.
  • Bardua M, Haftmann C, Durek P, Westendorf K, Buttgereit A, Tran CL, McGrath M, Weber M, Lehmann K, Addo RK, Heinz GA, Stittrich AB, Maschmeyer P, Radbruch H, Lohoff M, Chang HD, Radbruch A, Mashreghi MF. MicroRNA-31 Reduces the Motility of Proinflammatory T Helper 1 Lymphocytes. Front Immunol. 2018 Dec 6;9:2813. doi:10.3389/fimmu.2018.02813. eCollection 2018.
  • Matz M, Heinrich F, Zhang Q, Lorkowski C, Seelow E, Wu K, Lachmann N, Addo RK, Durek P, Mashreghi MF, Budde K. The regulation of interferon type I pathway-related genes RSAD2 and ETV7 specifically indicates antibody-mediated rejection after kidney transplantation. Clin Transplant. 2018 Dec;32(12):e13429. doi: 10.1111/ctr.13429.
  • Matz M, Heinrich F, Lorkowski C, Wu K, Klotsche J, Zhang Q, Lachmann N, Durek P, Budde K, Mashreghi MF. MicroRNA regulation in blood cells of renal transplanted patients with interstitial fibrosis/tubular atrophy and antibody-mediated rejection. PLoS One. 2018 Aug 13;13(8):e0201925. doi:10.1371/journal.pone.0201925. eCollection 2018.
  • Hammer Q, Rückert T, Borst EM, Dunst J, Haubner A, Durek P, Heinrich F, Gasparoni G, Babic M, Tomic A, Pietra G, Nienen M, Blau IW, Hofmann J, Na IK, Prinz I, Koenecke C, Hemmati P, Babel N, Arnold R, Walter J, Thurley K, Mashreghi MF, Messerle M, Romagnani C. Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells. Nat Immunol. 2018 May;19(5):453-463. doi: 10.1038/s41590-018-0082-6.
  • Kawano Y, Petkau G, Stehle C, Durek P, Heinz GA, Tanimoto K, Karasuyama H, Mashreghi MF, Romagnani C, Melchers F. Stable lines and clones of long-term proliferating normal, genetically unmodified murine common lymphoid progenitors. Blood. 2018 May 3;131(18):2026-2035. doi: 10.1182/blood-2017-09-805259.
  • Siracusa F, McGrath MA, Maschmeyer P, Bardua M, Lehmann K, Heinz G, Durek P, Heinrich FF, Mashreghi MF, Chang HD, Tokoyoda K, Radbruch A. Non-follicular reactivation of bone marrow resident memory CD4 T cells in immune clusters of the bone marrow. Proc Natl Acad Sci U S A. 2018 Feb 6;115(6):1334-1339. doi:10.1073/pnas.1715618115.
  • Popadić D, Heßelbach K, Richter-Brockmann S, et al. Gene expression profiling of human bronchial epithelial cells exposed to fine particulate matter (PM5) from biomass combustion. Toxicol Appl Pharmacol. 2018;347:10–22. doi:10.1016/j.taap.2018.03.024
  • Smiljanovic B, Radzikowska A, Kuca-Warnawin E, et al. Monocyte alterations in rheumatoid arthritis are dominated by preterm release from bone marrow and prominent triggering in the joint. Ann Rheum Dis. 2018;77(2):300–308. doi:10.1136/annrheumdis-2017-211649.
  • Ammari M, Presumey J, Ponsolles C, et al. Delivery of miR-146a to Ly6Chigh Monocytes Inhibits Pathogenic Bone Erosion in Inflammatory Arthritis. 2018;8(21):5972–5985. Published 2018 Nov 13. doi:10.7150/thno.29313.
  • Ammari M, Presumey J, Ponsolles C, et al. Delivery of miR-146a to Ly6Chigh Monocytes Inhibits Pathogenic Bone Erosion in Inflammatory Arthritis. Theranostics. 2018;8(21):5972–5985. Published 2018 Nov 13. doi:10.7150/thno.29313.
  • Siracusa F, Alp ÖS, Maschmeyer P, McGrath M, Mashreghi MF, Hojyo S, Chang HD, Tokoyoda K, Radbruch A. Maintenance of CD8(+) memory T lymphocytes in the spleen but not in the bone marrow is dependent on proliferation. Eur J Immunol. 2017 Nov;47(11):1900-1905. doi: 10.1002/eji.201747063.
  • Strauß R, Rose T, Flint SM, et al. Type I interferon as a biomarker in autoimmunity and viral infection: a leukocyte subset-specific analysis unveils hidden diagnostic options. J Mol Med (Berl). 2017;95(7):753–765. doi:10.1007/s00109-017-1515-7
  • Derer A, Böhm C, Grötsch B, Grün JR, Grützkau A, Stock M, Böhm S, Sehnert B, Gaipl U, Schett G, Hueber AJ, David JP. Rsk2 controls synovial fibroblast hyperplasia and the course of arthritis. Ann Rheum Dis. 2016 Feb;75(2):413-21.
  • Jürchott K, Schulz AR, Bozzetti C, Pohlmann D, Stervbo U, Warth S, Mälzer JN, Waldner J, Schweiger B, Olek S, Grützkau A, Babel N, Thiel A, Neumann AU. Highly Predictive Model for a Protective Immune Response to the A(H1N1)pdm2009 Influenza Strain after Seasonal Vaccination. PLoS One. 2016 Mar 8;11(3): e0150812.
  • Duroux-Richard I, Roubert C, Ammari M, Présumey J, Grün JR, Häupl T, Grützkau A, Lecellier CH, Boitez V, Codogno P, Escoubet J, Pers YM, Jorgensen C, Apparailly F. iR-125b controls monocyte adaptation to inflammation through mitochondrial metabolism and dynamics. 2016 Dec 29;128(26):3125-3136.
  • Alissafi T, Hatzioannou A, Ioannou M, Sparwasser T, Grün JR, Grützkau A, Verginis P. De novo-induced self-antigen-specific Foxp3+ regulatory T cells impair the accumulation of inflammatory dendritic cells in draining lymph nodes. J Immunol. 2015 Jun 15;194(12):5812-24.
Group Leader
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