Objectif Systemic lupus erythematosus (SLE) is a heterogeneous disease whereby an interplay of environmental, genetic and epigenetic factors lead to perturbation of complex biological networks culminating into diverse clinical phenotypes of varying severity. High throughput methods have allowed an “initial glimpse” into pathogenesis and have laid the foundations for a molecular-based taxonomy for personalized therapy. Based on our experience with the molecular characterization of SLE, a recently completed RNA sequencing analysis of 150 patients, and our track- record of “paradigm shift” trials in SLE, we will integrate data from multi-tissue analyses with novel technologies to improve its diagnosis, monitoring and therapy, and ask fundamental pathogenetic questions in systemic autoimmunity. More specifically, we will design gene expression panels and “expression profile”/”clinical trait” correlation matrices for diagnostics, personalized immunotherapy and improved clinical trial design. In a systematic multi-tissue approach, we will examine the role of somatic mutations in enhancing immune hyperactivity and the risk for lymphoma. The staggering (7-9:1) female predominance will be elucidated through elaborate genomic, epigenomic and microbiota analyses of family trios. Finally, we will be pursuing the innovative hypothesis that the fundamental abnormalities of SLE lie within the bone marrow hematopoietic stem cells (HSCs) - from which all cells that participate in the pathogenesis of SLE originate - and establish it as a unifying pathogenetic mechanism. By a combination of novel experimental analyses with single cell genomics, multi–omics, humanized animal models, genome editing and an “organ on-a-chip” device, we will validate HSCs as a therapeutic target. The utility of SLE research extends beyond its boundaries, by providing unique insights as to how the immune system recognizes self-constituents and maintains its homeostasis, and how gender impacts on disease biology. Champ scientifique medical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsRNAmedical and health sciencesbasic medicineimmunologyimmunotherapymedical and health sciencesbasic medicinephysiologyhomeostasis Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-2016-ADG - ERC Advanced Grant Appel à propositions ERC-2016-ADG Voir d’autres projets de cet appel Régime de financement ERC-ADG - Advanced Grant Institution d’accueil IDRYMA IATROVIOLOGIKON EREUNON AKADEMIAS ATHINON Contribution nette de l'UE € 2 355 000,00 Adresse SORANOU EFESIOU 4 115 27 Athina Grèce Voir sur la carte Région Αττική Aττική Κεντρικός Τομέας Αθηνών Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 2 355 000,00 Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire IDRYMA IATROVIOLOGIKON EREUNON AKADEMIAS ATHINON Grèce Contribution nette de l'UE € 2 355 000,00 Adresse SORANOU EFESIOU 4 115 27 Athina Voir sur la carte Région Αττική Aττική Κεντρικός Τομέας Αθηνών Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 2 355 000,00