EVALVE
Financiado
Biomechanics and signaling in models of congenital heart valve defects
Mechanical forces are fundamental to cardiovascular development and physiology. The interactions between mechanical forces and endothelial cells are mediated by mechanotransduction feedback loops. My lab is interested in understan...
Mechanical forces are fundamental to cardiovascular development and physiology. The interactions between mechanical forces and endothelial cells are mediated by mechanotransduction feedback loops. My lab is interested in understanding how hemodynamic forces modulate cardiovascular function and morphogenesis. Overall, our recent work is unraveling the biological links between mechanical forces, mechanotransduction and endothelial cell responses. The heart beats 2.6 billion times in a human lifetime and heart valves are amongst the most mechanically challenged structures of the body. The cardiac valves are made of endocardial cells (EdCs) and extracellular matrix components. Most valve diseases have their origins in embryogenesis, either as signs of abnormal developmental processes or the aberrant re-expression of fetal gene programs normally quiescent in adulthood.
This project is directed towards the elucidation of the biomechanical mechanism of mechanotransduction at the subcellular and molecular level and in addressing how EdCs integrate this information to form and maintain a functional cardiac valve. We will identify the mechanosensors at work in EdCs and their roles during cardiac valve development and repair. To do so, we will implement unique optical methodologies the lab has pioneered to characterize endocardial mechanotransduction: 1) Optical tweezing combined with mechanical stress reporters to test the mechanosensitivity of EdCs; 2) High resolution live microscopy and mathematical modeling to quantify mechanical forces; 3) 3D cell lineage studies to understand how cells respond and organize during pathological valve development. We will also use high-throughput mRNA- and ChIP-sequencing to characterize the transcriptional network activated by forces.
When completed this proposal will shed light on a critical, but little explored, aspect of congenital valve defects and will be useful for identifying new targets for therapeutic interventions.
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Duración del proyecto: 90 meses
Fecha Inicio: 2016-11-25
Fecha Fin: 2024-05-31
Fecha Fin: 2024-05-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2024-05-31
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-CoG-2015:
ERC Consolidator Grant
Cerrada
hace 9 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND ME...
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
175.92K€ |
Participante
1.20M€ |
Participante