Obiettivo 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. Campo scientifico medical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsRNAmedical and health sciencesbasic medicineimmunologyimmunotherapymedical and health sciencesbasic medicinephysiologyhomeostasis Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-2016-ADG - ERC Advanced Grant Invito a presentare proposte ERC-2016-ADG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-ADG - Advanced Grant Istituzione ospitante IDRYMA IATROVIOLOGIKON EREUNON AKADEMIAS ATHINON Contribution nette de l'UE € 2 355 000,00 Indirizzo SORANOU EFESIOU 4 115 27 Athina Grecia Mostra sulla mappa Regione Αττική Aττική Κεντρικός Τομέας Αθηνών Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 2 355 000,00 Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto IDRYMA IATROVIOLOGIKON EREUNON AKADEMIAS ATHINON Grecia Contribution nette de l'UE € 2 355 000,00 Indirizzo SORANOU EFESIOU 4 115 27 Athina Mostra sulla mappa Regione Αττική Aττική Κεντρικός Τομέας Αθηνών Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 2 355 000,00
