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About Sickkids
About SickKids

Julie Lefebvre, PhD

Research Institute
Scientist
Neurosciences & Mental Health

Chair Positions
Canada Research Chair
Developmental Neural Circuitry


Phone: 416-813-7654 ext. 309248
Email: julie.lefebvre@sickkids.ca

Brief Biography

Dr. Julie Lefebvre is a Scientist in the Neurosciences and Mental Health Program at The Hospital for Sick Children (SickKids). Her laboratory studies how nerve cells form specific patterns of neural connections that are essential for proper development and function of the nervous system. Her research will provide insights into how neural circuits assemble in the healthy brain, and how defects in these developmental pathways contribute to neurodevelopmental and brain disorders.

Dr. Lefebvre received her B.Sc. from McGill University. She earned her PhD at the University of Pennsylvania for her research on neuromuscular development in the laboratory of Dr. Michael Granato. For her postdoctoral training, she worked with Dr. Joshua Sanes at Harvard University to investigate molecular mechanisms of neuronal morphogenesis and circuit formation in the retina.  She joined SickKids in December 2013.

Research Interests

  • Neural development in retina and brain
  • Identification of genetic, molecular and cellular mechanisms essential for neural circuit formation and function
  • Genetic methods to study and manipulate single and subpopulations of neurons
  • Biological bases of neurodevelopmental disorders

Research Activities

In the developing brain, billons of nerve cells are precisely organized to drive complex functions such as sensations, locomotion, and language.   Neurons wire into circuits through a series of pathways that establish specific patterns of neuron branching and synaptic connections.  Perturbations to these wiring events in early life may lead to neurodevelopmental disorders.  Research in my laboratory seeks to:  1) understand how neurons develop and form circuits; 2) identify molecular pathways that specify neuron wiring; and 3) link alterations in neural development and circuit anatomy to abnormal brain function and neurodevelopmental disorders.   

To uncover the key molecular drivers that specify neuronal connectivity, we focus on cell-surface recognition molecules that mediate interactions between neuronal processes in retina and in brain. We are currently studying the multi-gene family of clustered protocadherins and their roles in providing molecular diversity and recognition specificity among single neurons to organize them into complex networks.  We apply a variety of approaches such as molecular and cellular assays, microscopy, viral and genetic tools to study gene function and neurons, and transgenic mice.   

Publications

Gibson D.A, Tymanskyj S., Yuan R.C., Leung H.C., Lefebvre J.L., Sanes J.R., Chédotal A., and Ma L. (2014).   Dendrite Self-Avoidance Requires Cell-Autonomous Slit/Robo Signaling in Cerebellar Purkinje Cells.  Neuron, 8: 1040-1056.

Lefebvre J.L., Kostadinov D., Chen W.V., Maniatis T., Sanes J.R.  (2012). Protocadherins mediate dendritic self-avoidance in the mammalian nervous system.  Nature, 488: 517-521.

Chen W.V., Alvarez F.J., Lefebvre J.L., Friedman B., Nwakeze C., Geiman E., Smith C., Thu C.A., Tapia J.C., Tasic B., Sanes J.R., Maniatis T. (2012).  Functional significance of isoform diversification in the protocadherin gamma subcluster.  Neuron, 75: 402-409.

Lefebvre J.L., Zhang Y.-F., Meister M., Sanes J.R.  (2008).  gamma-Protocadherins regulate neuronal survival but are dispensable for circuit formation in retina.  Development, 135: 4141-4151.

Jing L., Lefebvre J.L., Gordon L.R., Granato M.  (2009).  Wnt signals organize synaptic prepattern and axon guidance through the zebrafish unplugged/MuSK receptor.  Neuron, 61: 721-733.

 Lefebvre J.L., Jing L., Becaficco S., Franzini-Armstrong C., Granato M. (2007).  Differential requirements for MuSK and dystroglycan in generating patterns of neuromuscular innervation. Proc Natl Acad Sci USA, 104: 2483-2488.

Zhang J.*, Lefebvre J.L.*, Zhao S.*, Granato M.  (2004).  unplugged reveals a novel role for MuSK homologs in axonal pathway choice.  Nature Neuroscience, 7: 1303-1309.   * equal contribution

 Lefebvre J.L., Ono F., Puglielli C., Seidner G., Franzini-Armstrong C., Brehm P., Granato M.  (2004).  Increased neuromuscular activity causes axonal defects and muscular degeneration. Development 131: 2605-2618.