Objectif In the growing population of patients with congenital heart defects (CHD), while arrhythmias are not a major issue for children, they are a leading complication during adulthood. My hypothesis is that the origin of some life-threatening arrhythmias in adult, lies in cardiac structural and electrophysiological development. Thus, studying causes of CHDs may reveal key steps, mis-regulated in adult patients with CHD, leading to arrhythmias.Cardiac development and adult electrical function are finely regulated by transcription factors (TFs). Mutations in TFs have previously been linked to patients with CHD who are developing arrhythmias in adulthood. Hamamy syndrome is a newly described rare disease with CHD and rhythm disorders, caused by a mutation in IRX5 TF. In adult mice, Irx5 is known to regulate cardiac electrical function.I hypothesize that IRX5 mutation in Hamamy-affected patients, leads to misregulation of heart development, promoting arrhythmic events during adulthood.I already generated induced pluripotent stem (iPS) cells from Hamamy patients and a transgenic mouse expressing the Irx5 mutation.The project will be focused on three aims: 1. Characterizing the cardiac cellular function altered by IRX5 mutation, using iPS-derived cardiomyocytes; 2. Identifying cardiac structural and electrophysiological defects in the transgenic mouse; 3. Understanding the syndrome’s molecular mechanism.This study will provide immediate insight into understanding fundamental processes by which some arrhythmias in the adult originate in cardiac development. It may also help unveil the mechanism of age-related increase of arrhythmias in the general population. Finally, it will illustrate the ability of human iPS cell technology to model the abnormal functional phenotype of an inherited cardiac disorder. As such, it represents a promising model to study disease mechanisms, optimize patient care (personalized medicine), and aid in the development of new therapies. Champ scientifique medical and health sciencesclinical medicinecardiologycardiovascular diseasescardiac arrhythmianatural sciencesbiological sciencesgeneticsmutationmedical and health scienceshealth sciencespersonalized medicinemedical and health sciencesmedical biotechnologycells technologies Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2012-IIF - Marie Curie Action: "International Incoming Fellowships" Appel à propositions FP7-PEOPLE-2012-IIF Voir d’autres projets de cet appel Régime de financement MC-IIF - International Incoming Fellowships (IIF) Coordinateur CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS Contribution de l’UE € 179 766,30 Adresse RUE MICHEL ANGE 3 75794 Paris France Voir sur la carte Région Ile-de-France Ile-de-France Paris Type d’activité Research Organisations Contact administratif Anne Fagon (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Participants (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire UNIVERSITE DE NANTES Participation terminée France Contribution de l’UE Aucune donnée Adresse QUAI DE TOURVILLE 1 44035 NANTES CEDEX 1 Voir sur la carte Région Pays de la Loire Pays de la Loire Loire-Atlantique Type d’activité Higher or Secondary Education Establishments Contact administratif Sébastien Davy (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée