Genetics and pathophysiology of neurodevelopmental and Epileptogenic Disorders
Aetiologies of epileptogenic disorders are very heterogeneous and the group of epileptogenic developmental disorders (EDD), are now thought, in many cases, to be related to disruption of genetic factors/programs required for the coordinated timing of proliferation, migration and layering, as well as differentiation and function of neuronal cells.
Over the last few years, our group has significantly contributed in the progress of scientific and medical knowledge regarding subgroups of these disorders. In continuation with our previous studies, we will expand our investigations to focal cortical dyplasia (FCD) disorders, using large-scale complementary genomic studies. Through these genetic approaches we will also explore hypotheses of constitutive and somatic mosaic mutations underlying FCD.
In parallel to these genetic investigations, we will develop complementary functional studies focused on the tubulins and MT-dependent proteins (i.e., KIF5C, KIF2A, DYNC1H1 and TUBG1) recently shown to be involved in MCD spectrum, and develop animal models for FCD. The aim of these studies will be the characterization of disrupted biological and cellular processes whose roles appear to be relevant in brain development and organization. Priority will be given to the analysis of the consequences of depletion by shRNA approach and overexpression of mutated cDNA on progenitors proliferation, neuronal polarization, migration and differentiation. Also, MT-dependent processes such as MT-dependent transport in post mitotic neuronal cells will be thoroughly investigated.
- Identification of genes and genetic causes underlying malformation of cortical development (MCD) and focal cortical dysplasia (FCD)
- Caracterization and study of genetic, expression and epigenetic deregulations in the pathogeny of FCD (targeted studies of patients who went through surgical intervention and resection of epileptogenic dysplastic tissus)
- Definition and understanding of pathophysiological mechanisms underlying MCD using KI and conditional knock out mouse models for Tubg1, Kif2a, Kif5c and Dync1h1
Projects and investigations driven collaborations with groups at the IGBMC
Nadia Bahi Buisson (Hôpital Necker – IMAGINE. Paris, France)
Renzo Guerrini (Children's Hospital A. Meyer-University of Florence)
Izzie Jacques Namer, Service de Neuroimagerie, Hôpital de Hautepierre. Strasbourg. France
Vincent Laugel, Service de Pédiatrie, Hôpital de Hautepierre. Strasbourg. France
Mathieu Anheim (Service de Neurologie, Hôpital de Hautepierre. Strasbourg. France)
Christine Tranchant (Service de Neurologie, Hôpital de Hautepierre. Strasbourg. France)
Hélène Dollfus, Service de Génétique Médicale, Hôpital de Hautepierre , Strasbourg, France)
Thierry Bienvenu et Billuart Pierre (Insitut Cochin, Paris France)
Damien Sanlaville, Hospices Civils de Lyon – Lyon. France
Gaetan Lesca, Hospices Civils de Lyon – Lyon. France
Joseph Gleeson (Dept. Neurosciences and Pediatrics, University of California, San Diego).
Nicolas Cowan (NY University, USA)
Frédéric Saudou (Institut Curie, Orsay. France)
Laurent Nguyen (GIGA - Neurosciences, Université de Liège. Belgique)
David Keays (Institute of Molecular Pathology, Vienna. Austria)
Gencodys partners (http://www.gencodys.eu/)
- Jamel CHELLY - Scientific prize - Fondation NRJ - Institut de France - 2014
- Jamel CHELLY - Laureate - Fondation JED - 2013
- Jamel CHELLY - Research prize - Inserm - 2010
- Jamel CHELLY - Silver Medal - CNRS - 2002
- Jamel CHELLY - Grand prize - EDF - 2001
- Jamel CHELLY - Research prize "Life science" - Fondation Bettencourt Schueller - 1999
- Jamel CHELLY - Medicale and scientific research award - Fondation pour la Recherche Médicale (FRM) - 1999
- Jamel CHELLY - Bronze medal - CNRS - 1992
- Jamel CHELLY - Carré-Bessault prize - Académie des sciences - 1992
Nat Genet Oct. 3, 2016 .
J Med Genet June 29, 2016 .
Eur J Hum Genet June 29, 2016 .
PLoS One Feb. 26, 2016 ; 11:e0149717 .
Hum Mol Genet May 4, 2016 .
Eur J Med Genet Apr 2016 ; 59:249-56 .
Skelet Muscle Nov. 14, 2015 ; 5:40 .
Lancet Neurol Dec 2015 ; 14:1182-95 .
Eur J Hum Genet Sept. 23, 2015 ; 24:611-614 .
Eur J Med Genet Aug 2015 ; 58:416-8 .