BACKGROUND:
I obtained my PhD in Neuropharmacology with specific focus on myelin in the peripheral and central nervous systems and the effects of trace elements/heavy metals on its structure. I also studied the blood-brain barrier composed of the cerebral capillary endothelial cells which maintains homeostasis in the central nervous system by controlling the penetration into and removal of substances from the brain. Emerging research of the central nervous system indicates that endothelial cells of brain capillaries may represent a critical node in the microbiota-gut brain axis.
I began my work on serotoninergic system and psychiatric disorders associated with abnormal brain levels of serotonin (anxiety and depression). I conducted part of my research during this period as a visiting scientist in collaboration with other research scientists in the U.S (Boston, MA). I joined the laboratory of Prof. Jean-Pierre Changeux in 2003. The focus of my research in this laboratory was on neuronal nicotinic acetylcholine receptors (nAChRs), analysis of their response to chronic nicotine, and their ability to upregulate upon nicotine exposure depending on their subunits stoichiometry. My research has also been devoted to Autism Spectrum Disorders (ASD), and centered on the development of synaptic functions and plasticity of excitatory synapses, which underlie cognition. The main research topics were focused on studying the role of mutations in cell-adhesion molecules such as contactins in patients with ASD using culture of cortical neurons, automated quantification of neuritogenesis, and molecular 3D modeling. The study of the morphology of dendritic spines is crucial for understanding brain’s synaptic activity and all types of synaptopathies. One research axis has been focused on the morphology of dendritic spines reconstructed in 3D, and on the functional analysis of human neurons derived from skin biopsies of patients with mutations in synaptic proteins such as shank family (published in Scientific Reports, 2019).
CURRENT RESEARCH :
I am currently extending my expertise in human iPSC, to their transplantation in murine models (Vitrac and Cloëz-Tayarani, Stem Cell Research and Therapy, 2018; Vitrac et al, Sci. Rep. in press) to analyze the molecular mechanisms that control synaptic defects in the aging brain in vivo.
My objective is to develop new “humanized” models of Alzheimer Disease (AD) in order to understand the pathologic events that occur at early stages of this degenerative disease. This research axis remains in line with my previous work on nAChRs and brain ageing and should help in the discovery of new therapeutic targets in a context of research fully devoted to AD.
PhD SUPERVISION:
Hala Sahran (Co-director with G. Fillion, PhD obtained in 1997)
Oriane Mercati (Thesis Director, PhD obtained in Oct 2013)
Laura Gouder (Thesis Director, PhD obtained in Nov 2016)
Aline Vitrac (2016-2020)
Maria Llach (since Oct 2019)
Camille Thiberge (since Oct 2019)
Head of Studies of the Neuroscience Course : http://www.pasteur.fr/fr/enseignement/cours-pasteur/pole-mecanismes-du-vivant/development-and-plasticity-nervous-system
