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Mashreghi lab

With oligonucleotides against „diseased“ cells

Introduction
Members
Cooperation partners
Selected Publications

Therapeutic Gene Regulation

By discovering genes and non-coding RNAs implicated in the pathogenesis of osteoarthritis and other chronic inflammatory diseases, we aim to identify and characterise cells that trigger and drive the pathogenesis of rheumatic diseases. We apply state-of-the-art methods (particularly single-cell-sequencing approaches) to determine which genes and regulatory RNAs are selectively switched on in “disease causing” pathogenic cells versus healthy cells. Genes and regulatory RNAs which keep the pathogenic cells alive would be ideal targets for new therapies. The identification of such types of therapeutic targets will contribute to the development of advanced treatments that lead to remission in patients with rheumatic diseases. Since 2020, our technological expertise has also been applied to studying the pathogenesis of COVID-19.

Keywords
Regulatory RNA
Oligonucleotide therapy
Gene regulation
Single-Cell Sequencing
Chronic diseases

Deputy Scientific Director, Head of Programme Area 3, Systems Rheumatology Dr. Mir-Farzin Mashreghi Phone +49 (0)30 28460-752 mashreghi@drfz.de more
The project "Development of therapeutic oligonucleotides" is supported by the EFRE
Continue to Members

Group leader
Dr. rer. nat. Mir-Farzin Mashreghi

Scientists
Dr. med. Carl Goetzke (Klin. Wissenschaftler, together with T. Kallinich)
Dr. rer. nat. Marta Ferreira-Gomes
Dr. rer. nat. Frederik Heinrich
Dr. rer. nat. Pawel Durek

Ph.D. student
Mona Massoud

Technician
Gabriela Guerra

Associated group members
Dr. Pawel Durek (Bioinformatician)
Katrin Lehmann (Laboratory manager)
Antje Vester (Master Student)

The project "Development of therapeutic oligonucleotides" is supported by the EFRE
Continue to Cooperation partners
  • PD Dr. med. Tilmann Kallinich, Department of Pediatrics, Charité-Universitätsmedizin Berlin
  • Prof. Dr. Marcus Mall, Charité, Department of Pediatrics, Charité-Universitätsmedizin Berlin
  • Prof. Dr. Hans-Dieter Volk, BCRT
  • Prof. Dr. Petra Reinke, BCRT
  • Dr. Antigoni Triantafyllopoulou, DRFZ
  • Dr. Szandor Simmons, Charité
  • Dr. Tobias Alexander, Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin
  • Dr. Klemens Budde, Department of Nephrology, Charité-Universitätsmedizin Berlin
  • Prof. Dr. Falk Hiepe, Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin
  • Jürgen Wittmann, Molecular Immunology, Universitätsklinikum Erlangen
  • PD Dr. Anja Kühl, Institute for Pathology, Charité-Universitätsmedizin Berlin
  • Dr. Michael Lohoff, Institute for Medical Mikrobiology Philipps University Marburg
  • Dr. Stefan Kaufmann, Max-Planck-Institute for Infektion Biology
  • Dr. Fritz Melchers, DRFZ
  • Dr. Andreas Hutloff, DRFZ
  • Dr. Andrey Kruglov, DRFZ
  • Dr. Chiara Romagnani, DRFZ
  • Prof. Dr. Andreas Radbruch, DRFZ
  • Prof. Dr. Andreas Diefenbach, DRFZ
  • Prof. Dr. Max Löhning, DRFZ
  • Dr. Bastian Opitz, Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin
  • Prof. Dr. Simon Fillatreau, Institut Necker-enfants-malades (INEM), Paris, France.
  • George Goulielmos, Molecular Medicine and Human Genetics Laboratory, University of Crete, Heraklion, Greece.
  • Dr. Andreas Krüger, institute for Molecular Medicine, Goethe Universität Frankfurt
  • Dr. Dirk Ostareck, Department of Intensive Care, University Hospital Aachen
  • Dr. Antje Ostareck-Lederer, Department of Intensive Care University Hospital Aachen
The project "Development of therapeutic oligonucleotides" is supported by the EFRE
Continue to Selected Publications
  1. Witkowski, C.Tizian, M. Ferreira-Gomes, D. Niemeyer, T. C. Jones, F. Heinrich, S. Frischbutter, S. Angermair, T. Hohnstein, I. Mattiola, P. Nawrath, S. Mc Ewen, S. Zocche, E. Viviano, G. A. Heinz, M. Maurer, U. Kölsch, R. L. Chua, T. Aschman, C. Meisel, J. Radke15, B. Sawitzki, J. Roehmel, K. Allers, V.Moos, T.Schneider, L. Hanitsch, M. A. Mall, C. Conrad, H. Radbruch, C.U. Duerr, J. A. Trapan, E. Marcenaro, T. Kallinich, V. M. Corman, F. Kurth, L. E. Sander, C. Drosten, S. Treskatsch, P.Durek, A. Kruglov, A. Radbruch, M.F. Mashreghi*, and Andreas Diefenbach*(contributed equaly), Untimely TGFβ 1 responses in severe COVID-19 limit antiviral function of NK cells, Nature. 2021 Oct 25. doi: 10.1038/s41586-021-04142-6.
  2. Ferreira-Gomes, M., Kruglov, A., Durek, P., Heinrich, F., Tizian, C., Heinz, G. A., Pascual-Reguant, A., Du, W., Mothes, R., Fan, C., Frischbutter, S., Habenicht, K., Budzinski, L., Ninnemann, J., Jani, P. K., Guerra, G., Lehmann, K., Matz, M., Ostendorf, L., Heiberger, L., Chang, H.-D., Bauherr, S., Maurer, M., Schoenrich, G., Raftery, M., Kallinich, T., Mall, M. A., Angermair, S., Treskatsch, S., Doerner, T., Corman, V. M., Diefenbach, A., Volk, H.-D., Elezkurtaj, S., Winkler, T. H., Dong, J., Hauser, A. E., Radbruch, H., Witkowski, M., Melchers, F., Radbruch, A., Mashreghi, M.-F. SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself Nat Commun 12, 1961 (2021). https://doi.org/10.1038/s41467-021-22210-3
  3. Sunkara V, Heinz GA, Heinrich F, Durek P, Mobasheri A, Mashreghi MF*, Lang A*(contributed equally). Combining segmental bulk- and single-cell RNA-sequencing to define the chondrocyte gene expression signature in the murine knee joint. Osteoarthritis Cartilage. 2021 Mar 21:S1063-4584(21)00638-5. doi: 10.1016/j.joca.2021.03.007. Epub ahead of print. PMID: 33762205.
  4. Maschmeyer P, Heinz GA, Skopnik CM, Lutter L, Mazzoni A, Heinrich F, von Stuckrad SL, Wirth LE, Tran CL, Riedel R, Lehmann K, Sakwa I, Cimaz R, Giudici F, Mall MA, Enghard P, Vastert B, Chang HD, Durek P, Annunziato F, van Wijk F, Radbruch A, Kallinich T, Mashreghi MF. Antigen-driven PD-1+ TOX+ BHLHE40+ and PD-1+ TOX+ EOMES+ T lymphocytes regulate juvenile idiopathic arthritis in situ. Eur J Immunol. 2020 Dec 9. doi: 10.1002/eji.202048797. Epub ahead of print. PMID: 33296081.
  5. R Riedel, R Addo, M Ferreira-Gomes, G Heinz, F Heinrich, J Kummer, V Greiff, D Schulz, C Klaeden, R Cornelis, U Menzel, S Kröger, U Stervbo, R Köhler, C Haftmann, S Kühnel, K Lehmann, P Maschmeyer, MMcGrath, S Naundorf, S Hahne, Ö Sercan-Alp, F Siracusa, J Stefanowski, M Weber, K Westendorf, J Zimmermann, AE Hauser, ST Reddy, P Durek, HD Chang, MF Mashreghi*, A Radbruch*. Discrete populations of isotype-switched memory B lymphocytes are maintained in murine spleen and bone marrow, Nature communications; *equal contribution  doi: https://doi.org/10.1038/s41467-020-16464-6;
  6. 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. Epub 2019 Jun 7. PubMed PMID: 31149730; PubMed Central PMCID: PMC6771914.
  7. 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. PubMed PMID: 30574141; PubMed Central PMCID: PMC6291424.
  8. 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. Epub 2018 Nov 18. PubMed PMID: 30341925.
  9. 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. PubMed PMID: 30102719; PubMed Central PMCID: PMC6089438.
  10. 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. Epub 2018 Apr 9. PubMed PMID:
  11. 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. Epub 2019 Mar 4. PubMed PMID: 30833348.
  12. 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 establishe host-microbiota homeostasis. Nat Immunol. 2019 Apr;20(4):471-481. doi: 10.1038/s41590-019-0316-2. Epub 2019 Feb 18. PubMed PMID: 30778241.
  13. Maschmeyer P, Petkau G, Siracusa F, Zimmermann J, Zügel F, Kühl AA, Lehmann K, Schimmelpfennig S, Weber M, Haftmann C, Riedel R, Bardua M, Heinz GA, Tran CL, Hoyer BF, Hiepe F, Herzog S, Wittmann J, Rajewsky N, Melchers FG, Chang HD, Radbruch A, Mashreghi MF. Selective targeting of pro-inflammatory Th1 cells by microRNA-148a-specific antagomirs in vivo. J Autoimmun. 2018 May;89:41-52. Doi 10.1016/j.jaut.2017.11.005. Epub 2017 Dec 1. PubMed PMID: 29183643; PubMed Central PMCID: PMC5916452.
  14. Bothur E, Raifer H, Haftmann C, Stittrich AB, Brüstle A, Brenner D, Bollig N, Bieringer M, Kang CH, Reinhard K, Camara B, Huber M, Visekruna A, Steinhoff U, Repenning A, Bauer UM, Sexl V, Radbruch A, Sparwasser T, Mashreghi MF, Wah Mak T, Lohoff M. Antigen receptor-mediated depletion of FOXP3 in induced regulatory T-lymphocytes via PTPN2 and FOXO1. Nat Commun. 2015 Oct 13;6:8576. doi: 10.1038/ncomms9576. PubMed PMID: 26815406; PubMed Central PMCID: PMC4633965.
  15. Matz M, Fabritius K, Lorkowski C, Dürr M, Gaedeke J, Durek P, Grün JR, Goestemeyer A, Bachmann F, Wu K, Rudolph B, Schmidt D, Weber U, Haftmann C Unterwalder N, Lachmann N, Radbruch A, Neumayer HH, Mashreghi MF, Budde K Identification of T Cell-Mediated Vascular Rejection After Kidney Transplantatio by the Combined Measurement of 5 Specific MicroRNAs in Blood. Transplantation. 2016 Apr;100(4):898-907. doi: 10.1097/TP.0000000000000873. PubMed PMID: 26444957.
  16. Haftmann C, Riedel R, Porstner M, Wittmann J, Chang HD, Radbruch A, Mashreghi MF. Direct uptake of Antagomirs and efficient knockdown of miRNA in primary B and T lymphocytes. J Immunol Methods. 2015 Nov;426:128-33. doi: 1016/j.jim.2015.07.006. Epub 2015 Jul 15. PubMed PMID: 26187895; PubMe Central PMCID: PMC4655414.
  17. Weber JP, Fuhrmann F, Feist RK, Lahmann A, Al Baz MS, Gentz LJ, Vu Van D, Mages HW, Haftmann C, Riedel R, Grün JR, Schuh W, Kroczek RA, Radbruch A Mashreghi MF, Hutloff A. ICOS maintains the T follicular helper cell phenotype b down-regulating Krüppel-like factor 2. J Exp Med. 2015 Feb 9;212(2):217-33. doi: 10.1084/jem.20141432. Epub 2015 Feb 2. PubMed PMID: 25646266; PubMed Central PMCID: PMC4322049.
  18. Haftmann C, Stittrich AB, Zimmermann J, Fang Z, Hradilkova K, Bardua M, Westendorf K, Heinz GA, Riedel R, Siede J, Lehmann K, Weinberger EE, Zimmel D, Lauer U, Häupl T, Sieper J, Backhaus M, Neumann C, Hoffmann U, Porstner M, Chen W, Grün JR, Baumgrass R, Matz M, Löhning M, Scheffold A, Wittmann J, Chang HD, Rajewsky N, Jäck HM, Radbruch A, Mashreghi MF. miR-148a is upregulated by Twist1 and T-bet and promotes Th1-cell survival by regulating the proapoptotic gene Bim. Eur J Immunol. 2015 Apr;45(4):1192-205. doi: 10.1002/eji.201444633. Epub 2015 Jan PubMed PMID: 25486906; PubMed Central PMCID: PMC4406154
  19. Stittrich AB, Haftmann C, Sgouroudis E, Kühl AA, Hegazy AN, Panse I, Riedel R, Flossdorf M, Dong J, Fuhrmann F, Heinz GA, Fang Z, Li N, Bissels U, Hatam F, Jahn A, Hammoud B, Matz M, Schulze FM, Baumgrass R, Bosio A, Mollenkopf HJ, Grün J, Thiel A, Chen W, Höfer T, Loddenkemper C, Löhning M, Chang HD, Rajewsky N, Radbruch A, Mashreghi MF. The microRNA miR-182 is induced by IL-2 and promotes clonal expansion of activated helper T lymphocytes. Nat Immunol. 2010 Nov;11(11):1057-62. doi: 10.1038/ni.1945. Epub 2010 Oct 10. PubMed PMID: 20935646.
The project "Development of therapeutic oligonucleotides" is supported by the EFRE
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