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Canada research chair in neurodegeneration

Faculty of medicine
Department of psychiatry and neuroscience

Research center: CERVO Research Center

2601, chemin de la Canardière, local F-3471
G1J 2G3

E-mail address: jean-pierre.julien@fmed.ulaval.ca
Web site: http://www.vrr.ulaval.ca/bd/chercheur/fiche/341072.html

Mechanisms of neurodegeneration.
Fonctions of neuronal cytoskeleton and of neurofilaments.
Axonal transport.
Role of neuroinflammation.
Mouse models of human diseases.
Toxicity of protein aggregates.
Transgenic mouse techniques.
Therapy for ALS.

Research interests
The research program of Dr. Julien is focussed on the use of transgenic mouse models to elucidate the mechanisms of neurodegeneration associated with cytoskeletal abnormalities and genetic mutations causing amyotrophic lateral sclerosis (ALS). One aspect of his research seeks to better understand the deleterious effects that occur when neurofilaments accumulate on intracellular transports. He has produced numerous knockout mice in order to investigate the role and turnover of intermediate filaments in neuronal functions. Another aspect of his research aims to discover and demonstrate the molecular and cellular mechanisms of ALS that contribute to the loss of motor neurons. For instance, he is studying the role of inflammation and of chromogranin-mediated secretion of mutant superoxide dismutase in the pathogenesis of ALS. His research will have important implications for the discovery of new therapeutic targets and for the development of more effective treatments for neurodegenerative diseases.

Microinjection for production of transgenic mice, culture of ES cells and homologous recombination, time-lapse microscopy for measurement of intracellular motility of GFP proteins, proteomics, confocal microscopy, PCR, cloning of DNA, cryopreservation of embryos, genotyping of transgenic mice, cell culture.

Pathogenic mechanisms associated with neurofilament disorganization (CIHR).

The role of inflammation in pathogenesis of amyotrophic lateral sclerosis (CIHR).

Characterization of mice with targeted disruption of Als2 gene (CIHR).

Role of chromogranin-mediated secretion of superoxide dismutase mutants in ALS pathogenesis (Amyotrophic Lateral Sclerosis Association).

Mouse models to study the role of microglia in pathogenesis of ALS (The Robert Packard center for ALS research).

Engineered bone marrow stem cells (BMSCs) for treatment of CNS injuries and diseases (CIHR, principal researcher Dr. Serge Rivest).

Université Laval :
BMO-66783 Maladies génétiques et stratégies d'intervention sur mesure (Amyotrophic lateral sclerosis)
PHS-67097 Inflammation, brain repair and neurodegenerative diseases (Neurodegenerative diseases and transgenic mouse techniques)

Université McGill :
EXMD610 Course on transgenic mouse techniques

Main publications
Urushitani M, Sik A, Sakurai T, Nukina N, Takahashi R, Julien JP. Chromogranin-mediated secretion of mutant superoxide dismutase proteins linked to amyotrophic lateral sclerosis. Nat Neurosci. 2006; 9:108-118. Full text

Gowing G, Vallieres L, Julien JP. Mouse model for ablation of proliferating microglia in acute CNS injuries. Glia. 2006; 53:331-337. Full text

Millecamps S, Gentil BJ, Gros-Louis F, Rouleau G, Julien JP. Alsin is partially associated with centrosome in human cells. Biochim Biophys Acta. 2005; 1745:84-100. Full text

Gros-Louis F, Larivière R, Gowing G, Laurent S, Camu W, Bouchard, J-P, Meininger V, Rouleau GA, Julien J-P. A frameshift deletion in peripherin gene associated with amyotrophic lateral sclerosis. J Biol Chem. 2004; 279:45951-45956. Full text

Kriz J, Gowing G, Julien J-P. An efficient three-drug cocktail for motor neuron disease induced by mutant superoxide dismutase. Ann Neurol. 2003; 53:429-436. Full text

Team members
Makoto Urushitani, postdoctoral fellow
François Gros-Louis, postdoctoral fellow
Rodolphe Perrot, postdoctoral fellow
Geneviève Gowing, Ph.D. student
Samer Abou Ezzi, Ph.D. student
Florence deQuen, Ph.D. student
Roxanne Larivière, Ph.D., research assistant
Geneviève Soucy, M.Sc., research assistant
Christine Bareil, B.Sc., research assistant
Renée Paradis, B.Sc., research assistant
Nicolas Audet, technician
Daniel Phaneuf, research assistant