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Our main objective is to investigate the role of vasoactive paracrine/autocrine signals as well as vascular circulating factors at the interface between astrocytes and the brain microvasculature, and the role of the vascular niche in the regulation of neurogenesis, gliomagenesis and/or neoangio-genesis. Our team reinforced by clinicians (Neurosurgery, Neuroradiology and Anesthesiology and Critical Care services, Rouen Hospital), currently develops a continuum from cognitive projects to translational and clinical research programs to build innovative therapeutics.







Full page GPCR   -   Brain tumors
Our recent main contributions lie in the demonstration of the expression of the vasoactive neuropeptide urotensin II (UII) and its G protein coupled receptor (GPCR) UT in different brain human glioma biopsies and their role, as chemotaxic regulators, in tumor cell adhesion and migration via original UT signaling switch and inhibitory control of autophagic processes.
In vivo, UT activation favors proangiogenic cell type recruitment, neoangiogenesis, necrosis and activation of invasive mechanisms contributing to glioma growth whereas UT receptor “antagonists” exhibit anti-tumoral properties, constituting original treatment strategies against glioblastoma.

                                                                     Full page Brain hemorrhage

In another physiopathological context, a new hypothesis suggests an alteration of the microvascular glio-endothelial unit leading to delayed ischemia after subarachnoid hemorrhage. We established that UII and the UT receptor are expressed in brain microvascular compartments, that UT receptor antagonists prevent the ischemic neurological deficits post-hemorrhage in mice and that UII levels in patient CSF and plasma are correlated with macrovasospasm post-hemorrhage and delayed. We are currently developing new promising approaches to treat this neurovascular disease in transgenic mice (KO-UT and Kin human UT) we have conceptualized and produced. Thus, developing promising compounds for targeted physiological or therapeutic actions becomes real challenge. We determined the signaling profile of UT, activated by UII or synthetic analogue peptides and showed that activities of the urotensinergic system are differently modulated by peptide biased ligands, pointing out the importance of ligand-specific receptor signaling signature in the cellular behaviour of GPCRs.                                                             

Clinical investigations:

• Vincent Compère - CCPPRB - Endozepines levels in plasma of septic patients - 2004-2007.
• Nathalie Godard - PHRC "EvalHospitam" - Endozepines levels in plasma of anorexic patients 2007– 2012.
• François Proust - PHRC “FASHE” - Elderly and subarachnoid hemorrage - 2008- 2012.
• François Proust, Hélène Castel and Vincent Compère Rouen CHU promoter Young researcher - UII levels in CSF and plasma of SAH patients - 2010 -2012.
• Vincent Compère - CCPPRB - Urotensin levels in plasma of septic patients - 2010-2012.







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