Objetivo Thoracic aortic aneurysm and dissection (TAAD) is an important cause of morbidity and mortality in the western world. As 20% of all affected individuals have a positive family history, the genetic contribution to the development of TAAD is significant. Over the last decade dozens of genes were identified underlying syndromic and non-syndromic forms of TAAD. Although mutations in these disease culprits do not yet explain all cases, their identification and functional characterization were essential in deciphering three key aortic aneurysm/dissection patho-mechanisms: disturbed extracellular matrix homeostasis, dysregulated TGFbeta signaling and altered aortic smooth muscle cell contractility. Owing to the recent advent of next-generation sequencing technologies, I anticipate that the identification of additional genetic TAAD causes will remain quite straightforward in the coming years. Importantly, in many syndromic and non-syndromic families, significant non-penetrance and both inter- and intra-familial clinical variation are observed. So, although the primary genetic underlying mutation is identical in all these family members, the clinical spectrum varies widely from completely asymptomatic to sudden death due to aortic dissection at young age. The precise mechanisms underlying this variability remain largely elusive. Consequently, a better understanding of the functional effects of the primary mutation is highly needed and the identification of genetic variation that modifies these effects is becoming increasingly important. In this project, I carefully selected four different innovative strategies to discover mother nature’s own modifying capabilities in human and mouse aortopathy. The identification of these genetic modifiers will advance the knowledge significantly beyond the current understanding, individualize current treatment protocols to deliver true precision medicine and offer promising new leads to novel therapeutic strategies. Ámbito científico social sciencessociologydemographymortalitymedical and health sciencesclinical medicineangiologyvascular diseasesnatural sciencesbiological sciencesgeneticsmutationmedical and health scienceshealth sciencespersonalized medicinemedical and health sciencesbasic medicinephysiologyhomeostasis Programa(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Tema(s) ERC-2017-COG - ERC Consolidator Grant Convocatoria de propuestas ERC-2017-COG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-COG - Consolidator Grant Institución de acogida UNIVERSITEIT ANTWERPEN Aportación neta de la UEn € 1 987 860,00 Dirección PRINSSTRAAT 13 2000 Antwerpen Bélgica Ver en el mapa Región Vlaams Gewest Prov. Antwerpen Arr. Antwerpen Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 1 987 860,00 Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación neta de la UE Ampliar todo Contraer todo UNIVERSITEIT ANTWERPEN Bélgica Aportación neta de la UEn € 1 987 860,00 Dirección PRINSSTRAAT 13 2000 Antwerpen Ver en el mapa Región Vlaams Gewest Prov. Antwerpen Arr. Antwerpen Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 1 987 860,00