European Commission logo
français français
CORDIS - Résultats de la recherche de l’UE
CORDIS

Investigating the crosstalk between Notch and YAP/TAZ in sprouting angiogenesis

Description du projet

Interaction moléculaire pendant l’angiogenèse

L’angiogenèse est le processus physiologique qui permet la formation de nouveaux vaisseaux sanguins à partir de la vascularisation existante. Elle commence in utero et a lieu tout au long de la vie normale, mais elle joue également un rôle important dans la présence des maladies, notamment dans la progression du cancer. L’hypothèse de travail du projet Angio-NYT, financé par l’UE, est que la délimitation des voies moléculaires qui régulent l’angiogenèse débouchera sur de nouvelles thérapies anti-angiogéniques. L’objectif des chercheurs est d’étudier et de prédire le résultat des perturbations moléculaires de l’angiogenèse en combinant des modèles expérimentaux et informatiques. Cette démarche contribuera à l’identification des acteurs impliqués dans les voies de signalisation clés et ouvrira la porte à de nouveaux traitements.

Objectif

Our limited understanding of angiogenesis, the process leading to the formation of new blood vessels from pre-existing ones, hinders the design of new treatments for associated diseases such as cancer, ischemia, and diabetic retinopathy. It is well established that sprouting angiogenesis involves a process of endothelial cell phenotype selection mediated by the interaction between vascular endothelial growth factor (VEGF) and Notch signalling. Recently, it has been demonstrated that the Yes-associated protein (YAP) and the transcriptional coactivator with a PDZ-binding domain (TAZ), the main mediators of the Hippo signalling pathway, interact with VEGF and influence Notch signalling. However, it is still unclear how the effects of YAP/TAZ on Notch signalling contribute in regulating angiogenesis. In this project, I will adopt an approach combining experimental and computational techniques. First, I will culture endothelial cell monolayers on differently stiff substrates and I will perturb Notch via ligand-coated beads and YAP/TAZ activity via pharmacological inhibition. With the information deriving from these experiments, I will develop a unique agent-based computational model for angiogenesis, accounting for the interplay between Notch and YAP/TAZ. I will use this model to predict the effects of the Notch-YAP/TAZ crosstalk on angiogenesis. Finally, I will adapt previously established in vitro experimental systems recapitulating angiogenesis in three-dimensional environments. In these systems, I will vary the matrix stiffness, inhibit YAP/TAZ activation, perturb Notch signalling with ligand-coated beads, and measure the changes to parameters such as sprout and branch density and the dynamics of individual cell behaviour. This interplay between experimental and computational techniques will enhance our understanding of the crosstalk between Notch and Hippo-YAP/TAZ in regulating angiogenesis, with the potential to inspire new medical treatments.

Coordinateur

TECHNISCHE UNIVERSITEIT EINDHOVEN
Contribution nette de l'UE
€ 170 419,20
Adresse
GROENE LOPER 3
5612 AE Eindhoven
Pays-Bas

Voir sur la carte

Région
Zuid-Nederland Noord-Brabant Zuidoost-Noord-Brabant
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
€ 170 419,20

Partenaires (1)