Obiettivo Rheumatoid Arthritis is a common chronic autoimmune disease that affects approximately 1% of the adult population worldwide.Although its causes are largely unknown, it is clear that there is a considerable heritable component. In 2007, three genome-wide association studies (GWAS) as well as candidate gene approaches successfully increased the number of RA gene loci from two to five. More recently, a meta-analysis of these GWAS has been completed (Nature Genetics, in press). The most significant finding outside of the known RA risk loci was of a common polymorphism near the CD40 gene (odds ratio = 0.87 p = 5.1 x 10-9). While this represents a true disease gene, several questions remain to be answered to fully comprehend the role of CD40 mutations in RA pathogenesis. While this study provides direct evidence that CD40 is critical in RA pathogenesis, at least three crucial questions remain: 1) what is the exact common causal mutation? 2) Are there rare mutations that contribute to disease not accounted for in the genome-wide studies as they are designed to identify common mutations? 3) What is the biological relevance of both types of CD40 mutations? My proposed research will address these three critical questions by applying next generation genetic technologies (e.g. high-throughput Solexa sequencing) in large RA case-control collections available in the Plenge laboratory at Harvard Medical School (Outgoing Host Institute), together with functional immunology available in the Huizinga laboratory at Leiden University Medical Center (Return Host Institute). To achieve my goals, genetic and immunological resources will be combined to identify, validate and functionally characterise both common and rare functional mutations involved in the establishment of RA. This comprehensive approach will generate insight into a pathway relevant to disease development. Campo scientifico scienze mediche e della salutemedicina clinicareumatologiascienze mediche e della salutemedicina di baseimmunologiamalattie autoimmuniscienze naturaliscienze biologichegeneticamutazione Programma(i) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) FP7-PEOPLE-IOF-2008 - Marie Curie Action: "International Outgoing Fellowships for Career Development" Invito a presentare proposte FP7-PEOPLE-IOF-2008 Vedi altri progetti per questo bando Meccanismo di finanziamento MC-IOF - International Outgoing Fellowships (IOF) Coordinatore ACADEMISCH ZIEKENHUIS LEIDEN Indirizzo Albinusdreef 2 2333 ZA Leiden Paesi Bassi Mostra sulla mappa Regione West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Ellen Van Der Voort (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Contributo UE Nessun dato
