Obiettivo Chronic kidney disease (CKD) is a growing public health problem with a massively increased cardiovascular mortality. Patients with advanced CKD mostly die from sudden cardiac death and recurrent heart failure due to premature cardiac aging with hypertrophy, fibrosis, and capillary rarefaction. I have recently identified the long sought key cardiac myofibroblast progenitor population, an emerging breakthrough that carries the potential to develop novel targeted therapeutics. Genetic ablation of these Gli1+ perivascular progenitors ameliorates fibrosis, cardiac hypertrophy and rescues left-ventricular function. I propose that Gli1+ cells are critically involved in all major pathophysiologic changes in cardiac aging and uremic cardiomyopathy including fibrosis, hypertrophy and capillary rarefaction. I will perform state of the art genetic fate tracing, ablation and in vivo CRISPR/Cas9 genome editing experiments to untangle their complex mechanism of activation and communication with endothelial cells and cardiomyocytes promoting fibrosis, capillary rarefaction, cardiac hypertrophy and heart failure. To identify novel druggable targets I will utilize new mouse models that allow comparative transcript and proteasome profiling assays of these critical myofibroblast precusors in homeostasis, aging and premature aging in CKD. Novel assays with immortalized cardiac Gli1+ cells will allow high throughput screens to identify uremia associated factors of cell activation and inhibitory compounds to facilitate the development of novel therapeutics. This ambitious interdisciplinary project requires the expertise of chemists, physiologists, biomedical researchers and physician scientists to develop novel targeted therapies in cardiac remodeling during aging and CKD. The passion that drives this project results from a simple emerging hypothesis: It is possible to treat heart failure and sudden cardiac death in aging and CKD by targeting perivascular myofibroblast progenitors. Campo scientifico medical and health scienceshealth sciencespublic healthmedical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesclinical medicinecardiologycardiovascular diseasesarteriosclerosismedical and health sciencesbasic medicinephysiologyhomeostasismedical and health sciencesclinical medicinenephrologykidney diseases Parole chiave chronic kidney disease Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-StG-2015 - ERC Starting Grant Invito a presentare proposte ERC-2015-STG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-STG - Starting Grant Istituzione ospitante UNIVERSITAETSKLINIKUM AACHEN Contribution nette de l'UE € 1 497 888,00 Indirizzo Pauwelsstrasse 30 52074 Aachen Germania Mostra sulla mappa Regione Nordrhein-Westfalen Köln Städteregion Aachen Tipo di attività Higher or Secondary Education Establishments 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 € 1 497 888,00 Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto UNIVERSITAETSKLINIKUM AACHEN Germania Contribution nette de l'UE € 1 497 888,00 Indirizzo Pauwelsstrasse 30 52074 Aachen Mostra sulla mappa Regione Nordrhein-Westfalen Köln Städteregion Aachen Tipo di attività Higher or Secondary Education Establishments 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 € 1 497 888,00
