Centres Switzerland    
  Prof. Steffen Gay
Personal Steffen Gay is the Director at the Center for Experimental Rheumatology in the Department of Rheumatology at the University Hospital, Zürich, Switzerland. Within his centre, there are 3 to 5 clinicians and 9 to 10 research fellows, with the focus of their research being the molecular basis of rheumatic diseases and development and monitoring of novel treatment strategies.
Interests

Professor Gay’s experience is in all rheumatic diseases. However, his research is focused on the molecular and cellular basis of joint destruction in rheumatoid arthritis (RA), osteoarthritis (OA) and ankylosing spondylitis (AS). To better understand these mechanisms, the processes of synovial adhesion to cartilage and bone, the activation of synovial cells and the cellular interactions of the immune system are being studied. Major emphasis is focused at present on the epigenetic modifications in rheumatic and cardiovascular diseases.

Acetylation, methylation, ubiquination and microRNAs are studied with state of the art technologies to identify novel masterswitches in the pathways of gene regulation.
Suppressive subtractive hybridization and array technologies are used to establish complementary DNA libraries of genes, which are induced by various stimuli, including signalling via cytokine receptors and Toll-like receptors. Selected genes are analysed further for their function and role in the induction of transcription of genes, which control proliferation and survival of cells. Antisense constructs, ribozymes, short interfering RNA and antago-miRs are utilised to identify specific targets for future therapeutic interventions in the severe combined immunodeficient (SCID) mouse model for RA to explore such novel therapeutic strategies.

Molecular mechanisms of fibrosis in progressive systemic sclerosis (scleroderma) are another focus of Professor Gay’s research. Specifically, hypoxia-induced pathways, expression of chemokines and growth factors with regard to impaired angiogenesis and the excessive production of extracellular matrix are investigated. In close cooperation with the Department of Cardiology at the University Hospital of Zürich, endothelial function in both rheumatic and cardiovascular patients is also being studied.

Further information can be found at
www.zkf.uzh.ch/ResearchGroups/AlphabeticOrder/Gay.html and
www.rheumatologie.usz.ch
Research
Projects

1. Search for novel genes and epigenetic changes involved in the activation of synovial cells in RA
2. Gene transfer of novel inhibitors to inhibit synovial cell-mediated cartilage destruction
3. Microparticles containing miRNAs in the induction of signalling molecules in RA, SLE and systemic sclerosis
4. Molecular interactions affecting endothelial function in acute coronary syndromes (ACS)
5. Clinical and molecular studies on novel drug therapies utilising gene-array technologies to analyse for the ’proof of principle‘ and to detect signals of potential side effect
Recent
Publications

Kurowska-Stolarska M, Distler JH, Rudnicka W, Neumann E, Pap T, Wenger R, Jüngel A, Michel BA, Müller-Ladner U, Gay RE, Maslinski W, Gay S and Distler O. Id-2 induced by hypoxia promotes synovial fibroblast-dependent osteoclastogenesis. Arthr Rheum 60:3663-3675, 2009

Maurer B, Busch N, Jüngel A, Pileckyte M, Gay RE, Michel BA, Schett G, Gay S, Distler J, Distler O. The transcription factor Fra-2 induces progressive peripheral vasculopathy in mice closely resembling human systemic sclerosis. Circulation 120:2367-2376, 2009

Lefèvre S, Knedla A, Tennie C, Kampmann A, Wunrau C, Dinser R, Korb A, Schnäker EM, Tarner IH, Robbins PD, Evans CH, Stürz H, Steinmeyer J, Gay S, Schölmerich J, Pap T, Müller-Ladner U, Neumann E. Synovial fibroblasts spread rheumatoid arthritis to unaffected joints. Nat Med. [Epub ahead of print] Nov 8, 2009

Karouzakis E, Gay RE, Michel BA, Gay S, Neidhart M. DNA hypomethylation in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 30;60:3613-3622, 2009

Brock M, Trenkmann M, Gay RE, Michel BA, Gay S, Fischler M, Ulrich S, Speich R, Huber LC. Interleukin-6 Modulates the Expression of the Bone Morphogenic Protein Receptor Type II Through a Novel STAT3-microRNA Cluster 17/92 Pathway. Circ Res 104:1184-91, 2009

Stanczyk J, Pedroli DM, Brentano F, Sanchez-Pernaute O, Kolling C, Gay RE, Detmar M,
Gay S, Kyburz D. Altered expression of microRNA in the synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthr Rheum 58:1001-1009, 2008

Meinecke I, Cinski A, Baier A, Peters MA, Dankbar B, Willie A, Drynda A, Mendoza H, Gay RE, Hay RT, Ink B, Gay S, Pap T. Modification of nuclear PML protein by SUMO-1 regulates Fas-induced apoptosis in rheumatoid arthritis synovial fibroblasts. Proc Natl Acad Sci USA 104:5073-8, 2007.
   
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