Recalibrating Mechanotransduction in Vascular Malformations

Defects in the architecture of blood vessels (vascular malformations, or VMs) can have devastating consequences ranging from bleeding to stroke. Frequently, VMs occur in inoperable regions of the brain or brain stem. Thus, new and effective therapeutic approaches are urgently needed. This Leducq Transatlantic Network of Excellence is centered on the novel concept that a large group of VMs can be pharmacologically recalibrated to prevent maladaptive progression. Our underlying working hypothesis is that vascular architecture is shaped by hemodynamic forces due to blood flow and that VMs emerge when diseased cells are unable to adequately interpret or adapt to site-specific blood flow dynamics. Our international consortia has assembled a complementary group of experts in genetics, cell biology, biochemistry, molecular and stem cell biology to efficiently delve into the underlying problems experienced by mutant vascular cells and devise strategies to correct them. Individually, each member of the team has been working on either the characterization of VMs, from the cellular to the organismal level, or on the identification of relevant underlying mutations that impact vascular architecture. However, it is only together that they hold the ability to effectively tackle the problem and advance basic science discoveries into clinical applications. Importantly, the Network is committed to instruct and elevate the upcoming generation of scientists into this effort, as they will be trained at the interface of highly interdisciplinary science, contributing to discoveries and becoming poised to address emerging challenges.