Heisenberg Group for applied Matrixbiology and translational fibrosis research

Medicine 3

Head of Department:
Prof. Dr. med. univ. Georg Schett

The impact of fibroblasts in sclerodermia and rheumatoid arthritis

Head: Prof. Dr. med. Jörg Distler

Fibrotic diseases account for up to 45% of deaths in the developed world, yet there are almost no effective anti-fibrotic therapies for clinical use.

In our research group, we aim to investigate the molecular mechanisms underlying the aberrant tissue responses in fibrotic diseases (such as systemic sclerosis/scleroderma, chronic Graft-versus-Host-disease, pulmonary fibrosis, liver cirrhosis, renal fibrosis and hypertrophic scars) and to develop novel strategies for therapeutic intervention.

Our strategy is to identify de-regulated signaling pathways in samples of human fibrotic diseases ex vivo, to characterize their regulation and function in vitro and in vivo and to evaluate their potential for therapeutic intervention in murine models. Our evaluation included novel optical imaging strategies, which we run in close cooperation with the Max-Planck Institute of the Science of Light (Immunophysics).

Promising novel therapeutic approaches are transferred from bench-to-bedside with evaluation of the novel pharmacologic approach in clinical trials in patients with fibrotic diseases, often in cooperation with pharmaceutical industry.

  1. Tomcik M, Palumbo-Zerr K, Zerr P, Sumova B, Avouac J, Dees C, Distler A, Becvar R, Distler O, Schett G, Senolt L, Distler JH. Tribbles homologue 3 stimulates canonical TGF-β signalling to regulate fibroblast activation and tissue fibrosis. Ann Rheum Dis. 2015 Jan 20.
  2. Mallano T, Palumbo-Zerr K, Zerr P, Ramming A, Zeller B, Beyer C, Dees C, Huang J, Hai T, Distler O, Schett G, Distler JH. Activating transcription factor 3 regulates canonical TGFβ signalling in systemic sclerosis. Ann Rheum Dis. 2015 Jan 14.
  3. Palumbo-Zerr K, Zerr P, Distler A, Fliehr J, Mancuso R, Huang J, Mielenz D, Tomcik M, Fürnrohr BG, Scholtysek C, Dees C, Beyer C, Krönke G, Metzger D, Distler O, Schett G, Distler JH. Orphan nuclear receptor NR4A1 regulates transforming growth factor-β signaling and fibrosis. Nat Med. 2015 Jan 12.
  4. Iwamoto N, Vettori S, Maurer B, Brock M, Pachera E, Jüngel A, Calcagni M, Gay RE, Whitfield ML, Distler JH, Gay S, Distler O. Downregulation of miR-193b in systemic sclerosis regulates the proliferative vasculopathy by urokinase-type plasminogen activator expression. Ann Rheum Dis. 2014 Nov10.
  5. Venalis P, Kumánovics G, Schulze-Koops H, Distler A, Dees C, Zerr P, Palumbo-Zerr K, Czirják L, Mackevic Z, Lundberg IE, Distler O, Schett G, Distler JH. Cardiomyopathy in murine models of systemic sclerosis. Arthritis Rheumatol. 2014 Nov 4. doi: 10.1002/art.38942.
  6. Elhai M, Avouac J, Walker UA, Matucci-Cerinic M, Riemekasten G, Airò P, Hachulla E, Valentini G, Carreira PE, Cozzi F, Balbir Gurman A, Braun-Moscovici Y, Damjanov N, Ananieva LP, Scorza R, Jimenez S, Busquets J, Li M, Müller-Ladner U, Kahan A, Distler O, Allanore Y; … Distler JH…. A gender gap in primary and secondary heart dysfunctions in systemic sclerosis: a EUSTAR prospective study. Ann Rheum Dis. 2014 Oct 23. [Epub ahead of print].
  7. López-Isac E, Bossini-Castillo L, GGuerra S, Assassi S, Zhou X, PilarSimeón C, Ortego-Centeno N, Castellví I, Carreira P, Gorlova O, Beretta L, Santaniello A, Lunardi C, Hesselstrand R, Nordin A, Riemekasten G, Witte T, Hunzelmann N, Kreuter A, Distler JH, Voskuyl AE, deVries-Bouwstra J, Koeleman BP, Herrick A, Worthington J, Denton C, Fonseca C, Radstake TR, Mayes MD, Martin J; the Spanish Scleroderma Group. Identification of IL12RB1 as a novel systemic sclerosis susceptibility locus. Arthritis Rheumatol. 2014 Sep 8. [Epub ahead of print].
  8. Zerr P, Palumbo-Zerr K, Huang J, Tomcik M, Sumova B, Distler O, Schett G, Distler JH. Sirt1 regulates canonical TGF-β signalling to control fibroblast activation and tissue fibrosis. Ann Rheum Dis. 2014 Sep 1. [Epub ahead of print].
  9. Avouac J, Walker UA, Hachulla E, Riemekasten G, Cuomo G, Carreira PE, Caramaschi P, Ananieva LP, Matucci-Cerinic M, Czirjak L, Denton C, Ladner UM, Allanore Y;… Distler JH… Joint and tendon involvement predict disease progression in systemic sclerosis: a EUSTAR prospective study. Ann Rheum Dis. 2014 Aug 27. [Epub ahead of print].
  10. Avouac J, Palumbo-Zerr K, Ruzehaji N, Tomcik M, Zerr P, Dees C, Distler A, Beyer C, Schneider H, Distler O, Schett G, Allanore Y, Distler JH. The Nuclear Receptor Constitutive Androstane Receptor/NR1I3 Enhances the Profibrotic Effects of Transforming Growth Factor β and Contributes to the Development of Experimental Dermal Fibrosis. Arthritis Rheumatol. 2014 Nov;66(11):3140-50. [Epub ahead of print].
  11. Maurer B, Graf N, Michel BA, Müller-Ladner U, Czirják L, Denton CP, Tyndall A, Metzig C, Lanius V, Khanna D, Distler O; …Distler JH….. Prediction of worsening of skin fibrosis in patients with diffuse cutaneous systemic sclerosis using the EUSTAR database. Ann Rheum Dis. 2014 Jun 30. [Epub ahead of print].
  12. Tomcik M, Palumbo-Zerr K, Zerr P, Avouac J, Dees C, Sumova B, Distler A, Beyer C, Cerezo LA, Becvar R, Distler O, Grigorian M, Schett G, Senolt L, Distler JH. S100A4 amplifies canonical TGF-ß induced fibroblast activation in systemic sclerosis. Ann Rheum Dis. 2014 Apr 7.
  13. Beyer C, Huang J, Beer J, Zhang Y, Palumbo-Zerr K, Zerr P, Distler A, Dees C, Maier C, Munoz L, Krönke G, Uderhardt S, Distler O, Jones S, Rose-John S, Oravecz T, Schett G, Distler JH. Activation of liver X receptors inhibits experimental fibrosis by interfering with interleukin-6 release from macrophages. Ann Rheum Dis. 2014 Mar 11.
  14. Beyer C, Zenzmaier C, Palumbo-Zerr K, Mancuso R, Distler A, Dees C, Zerr P, Huang J, Maier C, Pachowsky ML, Friebe A, Sandner P, Distler O, Schett G, Berger P, Distler JH. Stimulation of the soluble guanylate cyclase (sGC) inhibits fibrosis by blocking non-canonical TGFβ signalling. Ann Rheum Dis. 2014 Feb 23.
  15. Beyer C, Zampetaki A, Lin NY, Kleyer A, Perricone C, Iagnocco A, Distler A, Langley SR, Gelse K, Sesselmann S, Lorenzini R, Niemeier A, Swoboda B, Distler JH, Santer P, Egger G, Willeit J, Mayr M, Schett G, Kiechl S. Signature of circulating microRNAs in osteoarthritis. Ann Rheum Dis. 2014 Feb 27.
  16. Zerr P, Vollath S, Palumbo-Zerr K, Tomcik M, Huang J, Distler A, Beyer C, Dees C, Gela K, Distler O, Schett G, Distler JH. Vitamin D receptor regulates TGF-β signalling in systemic sclerosis. Ann Rheum Dis. 2014 Jan 21.
  17. Distler A, Lang V, Del Vecchio T, Huang J, Zhang Y, Beyer C, Lin NY, Palumbo-Zerr K, Distler O, Schett G, Distler JH. Combined inhibition of morphogen pathways demonstrates additive antifibrotic effects and improved tolerability. Ann Rheum Dis. 2014 Jan 20.
  18. Jordan S, Distler JH, Maurer B, Huscher D, van Laar JM, Allanore Y, Distler O; on behalf of the EUSTAR Rituximab study group. Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group. Ann Rheum Dis. 2014 Jan 17.
  19. Zhang Y, Dees C, Beyer C, Lin NY, Distler A, Zerr P, Palumbo K, Susok L, Kreuter A, Distler O, Schett G, Distler JH. Inhibition of casein kinase II reduces TGFβ induced fibroblast activation and ameliorates experimental fibrosis. Ann Rheum Dis. 2014 Jan 15.
  20. López-Isac E, Bossini-Castillo L, Simeon CP, Egurbide MV, Alegre-Sancho JJ, Callejas JL, Roman-Ivorra JA, Freire M, Beretta L, Santaniello A, Airó P, Lunardi C, Hunzelmann N, Riemekasten G, Witte T, Kreuter A, Distler JH, Schuerwegh AJ, Vonk MC, Voskuyl AE, Shiels PG, van Laar JM, Fonseca C, Denton C, Herrick A, Worthington J, Assassi S, Koeleman BP, Mayes MD, Radstake TR, Martin J; Spanish Scleroderma Group. A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility. Arthritis Res Ther. 2014 Jan 9;16(1):R6.
  21. Moinzadeh P, Aberer E, Ahmadi-Simab K, Blank N, Distler JH, Fierlbeck G, Genth E, Guenther C, Hein R, Henes J, Herich L, Herrgott I, Koetter I, Kreuter A, Krieg T, Kuhr K, Lorenz HM, Meier F, Melchers I, Mensing H, Mueller-Ladner U, Pfeiffer C, Riemekasten G, Sárdy M, Schmalzing M, Sunderkoetter C, Susok L, Tarner IH, Vaith P, Worm M, Wozel G, Zeidler G, Hunzelmann N; and all participating DNSS centers. Disease progression in systemic sclerosis-overlap syndrome is significantly different from limited and diffuse cutaneous systemic sclerosis. Ann Rheum Dis. 2014 Jan 3.
  22. Mayes MD, Bossini-Castillo L, Gorlova O, Martin JE, Zhou X, Chen WV, Assassi S, Ying J, Tan FK, Arnett FC, Reveille JD, Guerra S, Teruel M, Carmona FD, Gregersen PK, Lee AT, López-Isac E, Ochoa E, Carreira P, Simeón CP, Castellví I, González-Gay MÁ; Spanish Scleroderma Group, Zhernakova A, Padyukov L, Alarcón-Riquelme M, Wijmenga C, Brown M, Beretta L, Riemekasten G, Witte T, Hunzelmann N, Kreuter A, Distler JH, Voskuyl AE, Schuerwegh AJ, Hesselstrand R, Nordin A, Airó P, Lunardi C, Shiels P, van Laar JM, Herrick A, Worthington J, Denton C, Wigley FM, Hummers LK, Varga J, Hinchcliff ME, Baron M, Hudson M, Pope JE, Furst DE, Khanna D, Phillips K, Schiopu E, Segal BM, Molitor JA, Silver RM, Steen VD, Simms RW, Lafyatis RA, Fessler BJ, Frech TM, Alkassab F, Docherty P, Kaminska E, Khalidi N, Jones HN, Markland J, Robinson D, Broen J, Radstake TR, Fonseca C, Koeleman BP, Martin J. Immunochip analysis identifies multiple susceptibility Loci for systemic sclerosis. Am J Hum Genet. 2014 Jan 2;94(1):47-61.
 
Contact
Prof. Dr. med. Jörg Distler
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Staff:

Jörg Distler
Christina Bergmann
Alina Soare
Chih-Wei Chen
Clara Dees
Rosebeth Kagwiria
Rita Weinkam
Sebastian Pötter
Ariella Zehender
Ruifang Liang
Debomita Chakraborty
Amelie Brandt
Lena Summa
Markus Luber
Xiaohan Xu
Thuong Trinh-Minh
Andrea-Hermina Györfi
Alexandru-Emil Matei
Yun Zhang
Vladyslav Fedorchenko
Ludwig Hallenberger
Benita Merlevede
Katja Dreißigacker (in maternity leave)
Regina Kleinlein


 
 
 
 
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