Objective Endothelial cells (ECs) exhibit a remarkable and unique plasticity in terms of redox biology and metabolism. They can quickly adapt to oxygen, nitric oxide and metabolic variations. Therefore, EC must be equipped with a selective and unique repertoire of redox and metabolic mechanisms, that play a crucial role to preserve redox balance, and adjust metabolic conditions in both normal and pathological angiogenesis. The identification of such redox signaling and metabolic pathways is crucial to the gaining of better insights in endothelial biology and dysfunction. More importantly, these insights could be used to establish innovative therapeutic approaches for the treatment of those conditions where aberrant or excessive angiogenesis is the underlying cause of the disease itself. However, the formation, actions, key molecular interactions, and physiological and pathological relevance of redox signals in ECs remain unclear. Here, by using cutting-edge real-time redox imaging platforms, and innovative molecular and genetic approaches in different in vivo animal models, we will (1) reveal the working of redox signaling in EC in health and disease, (2) shed light on the novel role for the mevalonate metabolic pathway in angiogenesis and (3) provide solid evidence, that manipulation of endothelial redox and metabolic state by genetic alteration of the redox rheostat UBIAD1, is a valuable strategy by which to block pathological angiogenesis in vivo. The ultimate objective is to open the way for the development of innovative (cancer) therapeutic strategies and complement the existing ones based on genetic or pharmacological manipulation of redox rheostats to balance oxidative or reductive stress in angiogenic processes. The success of this project is built upon our major expertise in the field of angiogenesis in small vertebrate animal models as well as on the collaborations with leading laboratories that are active in research on the pre-clinical stages for angiogenesis-rel Fields of science medical and health sciencesclinical medicinecardiologycardiovascular diseasesarteriosclerosismedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicinepathologymedical and health sciencesbasic medicinephysiologyhomeostasisnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Keywords Redox signaling zebrafish model tumor angiogenesis Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-CoG-2014 - ERC Consolidator Grant Call for proposal ERC-2014-CoG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Host institution UNIVERSITA DEGLI STUDI DI PADOVA Net EU contribution € 1 696 074,54 Address VIA 8 FEBBRAIO 2 35122 Padova Italy See on map Region Nord-Est Veneto Padova Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 696 074,54 Beneficiaries (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UNIVERSITA DEGLI STUDI DI PADOVA Italy Net EU contribution € 1 696 074,54 Address VIA 8 FEBBRAIO 2 35122 Padova See on map Region Nord-Est Veneto Padova Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 696 074,54 UNIVERSITA DEGLI STUDI DI TORINO Participation ended Italy Net EU contribution € 303 752,46 Address VIA GIUSEPPE VERDI 8 10124 Torino See on map Region Nord-Ovest Piemonte Torino Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 303 752,46