Prof. Oliver Distler

Keywords

Inflammation, fibroblasts, fibrosis, systemic sclerosis, non-coding RNAs

What we investigate

Our research focus is on fibroblasts and extracellular matrix remodeling/fibrosis and associated inflammatory pathways. It spans from a preclinical molecular biology program focusing on the identification and characterization of key molecules to a translational and clinical program with emphasis on precision medicine and phase 2/3 clinical trial design.

Our research in more detail

Abbildung Werner
The effect of H19X knock-down on myofibroblast development induced by TGFβ. Myofibroblasts were characterized by αSMA and stress fiber immunofluorescence staining (Pachera et al, J Clin Invest. 2020 Aug 17:135439).

Extracellular remodelling is a fundamental biological process occurring in many biologic and pathologic conditions including wound healing and fibrotic diseases. In our laboratory and clinical research, we are focusing on the chronic inflammatory autoimmune disease systemic sclerosis as a paradigm fibrotic disease. The overall goal is to identify molecular and cellular targets for therapy and develop them into targeted clinical therapies that are tested in appropriate clinical trials. To achieve this, we have used large scale screening (omics) approaches, and we developed novel advanced functional assays and a variety of animal models. We are using our biobanks to identify potential biomarkers for early proof of concept studies and disease prediction. We are also collaborating with the large international EUSTAR registry to model clinical trials and improve clinical trial design. We are contributing to the development of more sensitive disease measures in cooperation with our engineering partners. We eventually had the opportunity to join industry partners in the conduction of phase 2 and 3 registration trials, which lead to the clinical approval of new therapies for fibrotic diseases.

Selected publications

SKINTEGRITY.CH Principal Investigators are underlined:

  • Pachera E, Assassi S, Salazar GA, Stellato M, Renoux F, Wunderlin A, Blyszczuk P, Lafyatis R, Kurreeman F, de Vries-Bouwstra J, Messemaker T, Feghali-Bostwick CA, Rogler G, van Haaften WT, Dijkstra G, Oakley F, Calcagni M, Schniering J, Maurer B, Distler JH, Kania G, Frank-Bertoncelj M, and Distler O (2020). Long noncoding RNA H19X is a key mediator of TGF-β-driven fibrosis. J Clin Invest Aug 17:135439.
  • Renoux F, Stellato M, Haftmann C, Vogetseder A, Huang R, Subramaniam A, Becker MO, Blyszczuk P, Becher B, Distler JHW, Kania G, Boyman O, and Distler O. (2020).The AP1 transcription factor Fosl2 promotes systemic autoimmunity and inflammation by repressing Treg development. Cell Rep 31: 107826
  • Khanna D, Allanore Y, Denton CP, Kuwana M, Matucci-Cerinic M, Pope JE, Atsumi T, Bečvář R, Czirják L, Hachulla E, Ishii T, Ishikawa O, Johnson SR, De Langhe E, Stagnaro C, Riccieri V, Schiopu E, Silver RM, Smith V, Steen V, Stevens W, Szücs G, Truchetet ME, Wosnitza M, Laapas K, de Oliveira Pena J, Yao Z, Kramer F, and Distler O. (2020). Riociguat in patients with early diffuse cutaneous systemic sclerosis (RISE-SSc): randomised, double-blind, placebo-controlled multicentre trial. Ann Rheum Dis 79: 618-625.
  • Distler O, Highland KB, Gahlemann M, Azuma A, Fischer A, Mayes MD, Raghu G, Sauter W, Girard M, Alves M, Clerisme-Beaty E, Stowasser S, Tetzlaff K, Kuwana M, Maher TM; SENSCIS Trial Investigators (2019). Nintedanib for systemic sclerosis-associated interstitial lung disease. N Engl J Med 380: 2518-2528.