Chairman: Prof. Yannick Allanore
Yannick Allanore is Professor of Rheumatology at the Paris Descartes University in Paris since 2008. Professor ALLANORE is the Head of a research group working on the cardiovascular aspects of systemic sclerosis through clinical research programs and basic research ones, including genetic and cellular biology approaches (INSERM U1016, Cochin Institute). He has published over 335 papers in peer-review journals. Professor Allanore is a member of several professional bodies, including the French Rheumatology Society and the American College of Rheumatology. He is the elected chairman (2013-2019) of the The EUROPEAN Scleroderma Trials and Research group (EUSTAR). He is member of the Steering Committee of the Systemic Sclerosis World Congress in charge of Clinical Research committee.
Saint Jacques, Pavillon Hardy, 75014 Paris, France
e-mail : firstname.lastname@example.org
INSERM U1016, Cochin Institute, Batiment G Roussy – 4ème étage. Porte 410
8, rue Méchain, 75014 Paris, France
- Master degree: 1999, Paris Descartes University
- Medical Doctor: 2000, Paris Descartes University
- Certification in Rheumatology: 2001, Paris Descartes University
- Physician Doctor: 2004, Paris Descartes University, thesis on “Oxidative stress and systemic sclerosis”
- Assistant Professor, Paris Descartes University, Rheumatology A dpt, Cochin Hospital, 2005-2008
- Research Habilitation 2005; “Pathogenesis of systemic sclerosis”
- Post-doctoral researcher: INSERM U781, Necker Hospital, Paris Descartes University (head Pr Munnich), 2005-2008 “Genetic bases of systemic sclerosis”
- Post-doctoral researcher: INSERM U1016, Cochin, Hospital, Paris Descartes University, team Chronic inflammation and auto-immunity (Head Dr Chiocchia) 2010-2012
- Team ATIP/AVENIR, INSERM U1016, Cochin Institute, Translational genetics in systemic sclerosis, Head, 2013-present
- Professor of Rheumatology, Paris Descartes University, Rheumatology A dpt, Cochin Hospital, 2008-present.
Academic appointments: Professor of Rheumatology, Rheumatology A dpt, Cochin Hospital, Paris Descartes University
Major Research Interest: Genetic and pathophysiology of systemic sclerosis, cardiovascular involvement of systemic sclerosis, clinical trials in systemic sclerosis, endothelial progenitor cells in rheumatic diseases.
Members of National/International Societies: French Rheumatology Society, American College of Rheumatology, The EULAR Scleroderma Trials and Research group (EUSTAR) (chairman, re-elected in 2016), Association des Sclérodermies de France (head of the scientific committee)
Pubmed: 335 citations
Web of Science: 595 Publications; 9 320 citations; Index H: 49
Segretary: Prof. Otylia Kowal-Bielecka
Treasurer: Prof. Oliver Distler
Gloriastrasse 25, 8091 Zürich, Switzerland
Phone: +41 44 255 29 70; E-Mail: email@example.com
2004/2005 Specialization in Internal Medicine
2006 Specialization in Rheumatology
2012 Certificate of Advanced Studies in Healthcare Management, University of St. Gallen, Switzerland
1997-1998 Resident, Department of Internal Medicine I, University of Regensburg, Germany
1998-2002 Fellow, Center of Experimental Rheumatology, University of Zurich, Switzerland
2002-2003 Fellow, Department of Clinical Immunology, University of Zurich, Switzerland
2004-2006 Fellow, Department of Rheumatology, University of Zurich, Switzerland
2006-2009 Attending Physician (Oberarzt), Department of Rheumatology, University of Zurich, Switzerland
2006-2013 Privatdozent, University of Zurich, Switzerland
2009-2016 Senior Attending Physician (Leitender Arzt) and Director Scleroderma Program, Department of Rheumatology, University of Zurich, Switzerland
2012 Visiting Professor, University of Gothenburg, Sweden
2013-2016 Professor ad personam of Inflammatory Rheumatology, University of Zurich, Switzerland
2015-2017 Adjunct Professor, University of Florence, Italy
2015 Visiting Professor, Stanford University, USA
2016 Full Professor of Rheumatology, University of Zurich, Switzerland
2015-2018 Hochspezialisierte Medizin-2 (HSM-2). Topic: Gezielte und interdisziplinäre Behandlung schwerer immunvermittelter Erkrankungen.
2016-2018 SNF Project Grant. Topic: Long non-coding RNAs in systemic sclerosis and other fibrotic diseases.
2016-2018 Swisslife- Foundation. Topic: Development of systemic autoimmunity through Fra2 mediated regulatory T cell deficiency.
2016-2018 Helmut Horten Foundation. Topic: The role of microRNA-125b in systemic sclerosis.
2016-2019 Skintegrity, Flagship Project UZH-ETH. Topic: Systemic sclerosis.
2017-2018 Kurt und Senta-Herrmann-Foundation. Topic: Development of systemic autoimmunity through Fra2 mediated regulatory T cell deficiency.
2017-2018 Baugarten Foundation. Topic: Einfluss von körpereigenen Knorpelabbauprodukten auf die Hämatopoese und deren Relevanz in schmerzhaft entzündlichen Knochenmarkveränderungen.
2017-2020 Foundation for Research in Science and the Humanities at the University of Zurich (STwF).Topic: The role of the bromodomain proteins in arthritis susceptibility and synovial biology.
2018-2021 Personsonalized Health and Related Technologies – Swiss Personalized Health Network (PHRT-SPHN) Grant. Topic: PRECISE: Identification of biomarkers and therapeutic targets in inflammatory disease immunotherapy by high-dimensional single cell analysis and cluster proteomics.
Master, PhD and MD students: 14 Master/MD/PhD students between 1998 and 2017 (successfully completed Master/MD/PhD thesis); Current: Fabian Brennecke, Sebastian Burgener, Rucsandra Dobrota, Caroline Evers, Jasmin Hérnandez, Matthew Kassier, Dzulija Kiceva, Anastasiia Kozlova, Simon Kuster, Geraldine Lautenbach, Fiona Martin, Chantal Meier, Thomas Moser, Dominic Moret, Elena Pachera, Florian Renoux, Michal Rudnik, Janine Schniering, Noah Schweizer, Mara Stellato, Kabriya Charles Thavaratnam, Michele Trussardi.
Postdocs and senior group leaders: 8 postdocs/senior group leaders between 2001 and 2017; Current: Przemyslaw Blyszczuk, Stefan Dudli, Mojca Frank-Bertoncelj, Suzana Jordan, Astrid Jüngel, Gabriela Kania, Emmanuel Karouzakis, Kerstin Klein, Britta Maurer, Michel Neidhart, Caroline Ospelt, Masaya Yokota, Wanlong Wu.
- Clinical examination course (MeF): Internal Medicine, 8 hours per year
- Human biology block course (MNF): Pathophysiology and molecular biology of vegetative systems, 2 x 1.5 weeks/year
- Basic clinical lecture series (MeF): Infectious diseases and immunology, 2 hours front lectures per year
- Adcanced clinical lecture series (MeF): Differential diagnosis of the musculosceletal system –Rheumtology, 8 hours front lectures/year
Since 2013 Secretary and Board Member of EUSTAR (EULAR Scleroderma Trials and Research Group)
Since 2014 President Scientific Committee Swiss Society of Rheumatology (SGR)
Since 2014 President and/or Co-President of Scientific Advisory Boards of three randomized controlled clinical phase 2/3 registration trials in systemic sclerosis
Since 2014 Member of Scientific Advisory Board of multiple additional phase 2/3 randomized controlled clinical trials and investigator-initiated proof of concept studies in systemic sclerosis
Since 2015 Scientifc Advisory Board GILS (Gruppo Italiano per la Lotta alla Sclerodermia) Foundation
Since 2016 Editorial Board Journal of Scleroderma and Related Disorders
Since 2016 Scientifc Advisory Board of the AbbVie Rheumatology Grant
Since 2016 Scientific Advisory Board Member of the Hartmann Müller Foundation
Since 2016 Senate Member of SAMW (Swiss Academy of Medical Sciences), Representative of Medical Faculty, University of Zurich
Since 2017 Board Member, SCQM Foundation (Swiss Clinical Quality Management in Rheumatic Diseases)
Active memberships in scientific societies, fellowships in renowned academies
Since 2016: Member Walter-Siegenthaler-Gesellschaft für Fortschritte in der Inneren Medizin
Organisation of conferences
Involved in the organization of 19 conferences, including chair and scientific organization committee of the following important meetings:
- Abstract selection committee of the American College of Rheumatology (ACR) and abstract chair of the section “Pathophysiology of scleroderma and related diseases, Annual ACR meeting 2006-2007
- Co-Chair and Co-organizer of the congress „Controversies in connective tissue diseases”, Florence 2007, Zurich 2008 and London 2009
- Co-Chair and Co-organization of the congress „Expert Meeting on pulmonary hypertension”, Frankfurt 2010
- Steering committee Member of the Systemic Sclerosis World Congress, Florence 2010, Madrid 2012, Rome 2014, Lisbon 2016, Bordeaux 2018
- International Advisory Board for the Annual European Workshop of Rheumatology Research (EWRR) since 2011
- Program Committee of Member the Annual European League against Rheumatism (EULAR) congress Berlin 2012, London 2013 and Paris 2014
- President Annual Meeting of the Swiss Society of Rheumatology (SGR) 2014-2018
- Program Committee of the EUSTAR educational course on systemic sclerosis since 2015
Major prizes, awards, fellowships
2001 Young Investigator Research Career Award of the University of Zurich
2002 European Workshop of Rheumatology Young Investigators Award
2002 Academic Exchange Travel Award of ACR and EULAR
2003 Abbott Award Basic Science
2005: Warnery Award of the Swiss Society for Rheumatology
2009: Pfizer Award Rheumatology/Clinical Immunology
Our research focus is on systemic sclerosis (SSc), which is a difficult to treat chronic autoimmune disease with high morbidity and mortality. Skin fibrosis is the hallmark of this disease. Our research program spans from a preclinical program focusing on the identification and characterization of key molecules and intracellular signaling cascades that are driving the disease process to a translational and clinical program with emphasis on precision medicine and phase 2/3 clinical trial design. Our Center has been awarded a EULAR Center of Excellence due to the scientific achievements in these areas.
In our preclinical program, we could show that signaling via the Serotonin receptor 2b on fibroblasts is a key mechanism to promote fibrosis in a TGF-b dependent manner in vitro, but also in different animal models of skin fibrosis in vivo (Dees et al, 2011). These promising results led us to perform a proof of concept clinical study in patients with SSc using biomarkers as the primary endpoint. In the investigator-initiated study, we found strong effects on key features of fibrosis confirming the animal studies (Distler et al, paper in preparation). Collaborating with industry, we now designed a phase 3 registration study which has been positively evaluated by the regulatory agencies EMA and FDA and will start later in 2018. We could improve clinical trials design of this study be using biostatistical modeling with large databases, which we co-initiated and organized (Maurer et al 2015, Dobrota et al 2016).
Another focus in the laboratory are epigenetics and non-coding RNAs. In SSc, we have focused on miRNAs as a class of non-coding RNAs. We were the first to show that miR-29 is down regulated in SSc by TGF-β, PDGF-B, and IL-4 and directly contributes to fibrosis by targeting collagen mRNA [Maurer et al, 2010]. This resulted in a patent filed for the use of miR-29 in scleroderma. Furthermore, we have characterized additional miRNAs such as miR-193b and miR-145 as important posttranscriptional regulators in SSc contributing to diverse pathophysiological processes like vasculopathy and fibrosis (Iwamoto et al 2014, Vettori et al, in preparation). Recently, we have identified the novel long non-coding RNA H19X as a key mediator of TGFb profibrotic effects in a variety of mesenchymal cells. Knock-down of H19X completely prevented the profibrotic effects of TGFb. RNA Sequencing and ATAC-Seq showed that these effects are likely mediated by modification of the transcription factor AP-2. H19 X was found to be upregulated in tissues of several fibrotic diseases including SSc (Pachera et al, manuscript in preparation).
Our laboratory has been centrally involved in the identification and characterization of animal models of SSc. For example, there was until recently no animal model available that resembled the vascular changes in human SSc. The further characterization and validation of the Fra-2 tg mice by our groups enabled the use of this animal model as a preclinical model for the vascular (and fibrotic) manifestations of SSc, and it is now one of the most frequently used preclinical model for SSc. We could show that these mice develop skin fibrosis likely mediated by initial apoptosis of endothelial cells, and that the vascular lesions largely resembles finding observed in human SSc tissues (Maurer et al, 2009; Maurer et al, 2012). In addition, we showed that VEGF tg mice develop skin fibrosis in a dose-dependent manner and are more susceptible to inducible models of fibrosis such as the bleomycin model than control wt mice (Maurer et al, 2014).
Translational of our findings into potential clinical applications has always been a focus of our research. We had observed that some of our targets for intervention showed promising results in the animal models, but did not show effects in human proof of concept studies. Using the example of tyrosine kinase inhibitors (Distler, 2007), we could show that the anti-fibrotic effects were strongly depending on the level of activation of the targets, and that in the human disease target activation was often much lower than in the used animal models (Maurer et al, 2013). This lead to change in the use of animal models in preclinical characterization and to updated recommendations how to use animal models in SSc (Jordan et al, 2013). It also highlighted the importance of precision medicine in this disease and led to the development of a molecular imaging program. In this Sinergia funded program, we could recently show that molecular imaging using SPECT or PET/CT in mouse models of SSc allows individual identification of activated pathway involving folate receptor beta (FR-β) and integrin avβ3, paving the way for precision medicine approached against this pathways (Schniering et al, in preparation).
Total number of primary research publications: 179
Citations: 10’936, H-Index: 53 (Web of Science, February 2018)
Ten most important papers
(1) Distler JH, Jüngel A, Huber LC, Schulze-Horsel U, Zwerina J, Gay RE, Michel BA, Hauser T, Schett G, Gay S, Distler O. Imatinib mesylate decreases the production of extracellular matrix and prevents the development of experimental dermal fibrosis. Arthritis Rheum 2007, 56:311-22. Citations: 247
This preclinical proof of concept study for inhibition of fibrosis by targeting tyrosine kinases led to several clinical studies in systemic sclerosis and other fibrotic diseases.
(2) Distler JH, Jüngel A, Huber LC, Seemayer CA, Reich III CF, Gay RE, Michel BA, Fontana F, Gay S, Pisetsky DS, Distler O. The induction of matrix metalloproteinase and cytokine expression in synovial fibroblasts stimulated with immune cell microparticles. P Natl Acad Sci USA 2005, 102:2892-7. Citations: 167
In this report, the strong functional effects of microparticles on the destructive potential of rheumatoid arthritis synovial fibroblasts were described leading to a series of publications in high rank journals in this field.
(3) Maurer B, Stanczyk J, Jüngel A, Akhmetshina A, Trenkmann M, Brock M, Kowal-Bielecka O, Gay RE, Michel BA, Distler JHW, Gay S, Distler O. miR-29 is a key regulator of collagen expression in systemic sclerosis. Arthritis Rheum 2010, 62:1733-43. Citations: 258
This was the first report on disturbed expression and regulation of microRNAs in systemic sclerosis and their contribution to the development of fibrosis, also filed as a patent.
(4) Distler O, Distler JH, Scheid A, Acker T, Hirth A, Rethage J, Michel BA, Gay RE, Muller-Ladner U, Matucci-Cerinic M, Plate KH, Gassmann M, Gay S. Uncontrolled expression of vascular endothelial growth factor and its receptors leads to insufficient kin angiogenesis in patients with systemic sclerosis. Circ Res 2004, 95:109-16. Citations: 194
The first in depths analysis on the differential expression and regulation of vascular endothelial growth factor and its key role in the disturbed angiogenesis of systemic sclerosis.
(5) Dees C, Akhmetshina A, Reich N, Jüngel A, Beyer C, Krönke G, Zwerina J, Reiter R, Alenina N, Maroteaux L, Gay G, Schett G, Distler O*, Distler JHW.* Platelet-derived serotonin links vascular disease and tissue fibrosis. *contributed equally. J Exp Med 2011, 208:961-72. Citations: 114
This comprehensive analysis of serotonin receptor 2 signaling in systemic sclerosis led to an investigator-initiated clinical proof of concept study from my group with positive results. Currently, a large scale phase III randomized placebo-controlled international multicenter registration study is initiated with me as the global PI.
(6) Distler O, del Rosso A, Giacomelli R, Cipriani P, Conforti ML, Guiducci S, Gay RE, Michel BA, Brühlmann P, Müller-Ladner U, Gay S, Matucci-Cerinic M. Angiogenic and angiostatic factors in systemic sclerosis: Increased levels of vascular endothelial growth factor (VEGF) are a feature of earliest disease stages and are associated with the absence of fingertip ulcers, Arthritis Res Ther 2002; 4:R11. Citations: 173
This study established for the first time the dysbalance of angiogenic and angiostatic factors in systemic sclerosis and associated these findings with vascular manifestations of the disease.
(7) Distler JH, Jüngel A, Michel BA, Gay RE, Matucci-Cerinic M, Marti HH, Gay S, Distler O. Dermal hypoxia increases the production of extracellular matrix proteins in systemic sclerosis. Arthritis Rheum 2007; 56:4203-4215. Citations: 91
Herein, we could show that hypoxia is an independent driver of fibrosis leading to a vicious circle of fibrosis accumulation and hypoxia. These findings had important impact on the concept of fibrosis as a multifactorial disease that might require multitargeted treatments.
(8) Maurer B, Graf N, Michel BA, Müller-Ladner U, Czirják L, Denton CP, Tyndall A, Metzig C, Lanius V, Khanna D, Distler O; on behalf of EUSTAR co-authors. Prediction of worsening of skin fibrosis in patients with diffuse cutaneous systemic sclerosis using the EUSTAR database. Ann Rheum Dis. 2015; 74(6):1124-31. Citations: 28
This study defined novel inclusion criteria for randomized controlled clinical trials in systemic sclerosis taking advantage of the large EUSTAR database, which was co-founded by me together with several other colleagues. Several of the ongoing phase three registration trials are using these novel inclusion criteria.
(9) 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 2015; 74(6):1188-94. Citations: 78
Using innovative clinical trial design, we could gather evidence for effects of the anti-CD20 therapy Rituximab in patients with systemic sclerosis.
(10) Maurer B, Busch N, Jüngel A, Pileckyte M, Gay RE, Michel BA, Schett G, Gay S, Distler J, Distler O. Transcription factor fos-related antigen-2 induces progressive peripheral vasculopathy in mice closely resembling human systemic sclerosis. Circulation 2009; 120:2367-76. Citations: 57
This was the first description of the Fra-2 tg mouse model as a model of systemic sclerosis. Fra-2 tg mice are nowadays frequently used mouse models for the disease.