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Acting Director and Senior Scientist, Vision Program, Ottawa Hospital Research Institute
Associate Professor, Department of Ophthalmology, University of Ottawa
Associate Professor, Department of Biochemistry, Microbiology and Immunology, University of Ottawa
Research Interests
Mouse models of retina and optic nerve development
Morphogen trafficking in neurons
Stem cell transplantation to the retina
Research Activities
We are interested in the general problem of how cell number and fate are regulated in the developing brain. Unraveling how signaling pathways and genes that control these processes is key to understanding brain function but also important for the development of cell and drug therapies to treat degenerative diseases of the brain. We use the mammalian retina as a model to address these questions because its development is well characterized and it is a tractable system for experimental manipulation. Gene knockouts of important signaling pathways in the retina are generally not lethal and retinal tissue can be cultured in vitro, allowing for rapid manipulation of signaling and gene expression. The 6 neurons and one glial cell type that make up the adult retina develop sequentially from a pool of multipotential neuroepithelial cells. We have been studying how cell extrinsic factors, including morphogens of the Wnt and Hedgehog signaling pathways, contribute to cell diversification in this tissue. We have shown that Wnt signaling plays an important role in patterning the eye and that Sonic hedgehog signaling from retinal neurons drives cell cycle and maintains progenitors in an undifferentiated state. Projects in the lab include the identification of Wnt and Hedgehog target genes in retinal progenitors, elucidation of the mechanisms of Hedgehog movement and trafficking in neurons, and development of in vitro strategies to promote retinal stem cell growth and differentiation for cell transplantation to the retina.
Funding Sources
Canadian Cancer Society
Canadian Institutes of Health Research
Stem Cell Network of Canada
Foundation Fighting Blindness
How to apply
Student and postdoctoral applicants are encouraged to contact Dr. Valerie Wallace directly. vwallace@ohri.ca.
Selected Publications
Wang, Y., Dakubo, G., Mazerolle, C, Thurig, S., Shiga, S. and Wallace, V. A. 2005. Retinal ganglion cell-derived Sonic hedgehog locally controls proliferation and the timing of RGC development in the embryonic mouse retina. Development 132:5103-5113.
Furimsky, M. and Wallace, V.A. 2006. Complementary Gli activity mediates early patterning of the mouse visual system. Developmental Dynamics 235:594-605.
Yu, C., Mazerolle, C., Thurig, S., Pacal, M., Bremner, R. and Wallace, V. A. 2006. Direct and indirect effects of hedgehog pathway activation in the mammalian retina. Molecular Cellular Neuroscience. 32:274-282.
Liu, H., Thurig, S., Mohamed, O., Dufort D. and Wallace V. A. 2006. Mapping Canonical Wnt signaling in the developing and adult retina. IOVS 47(11):5088-5096.
Liu, H., Xu, S., Wang Y., Mazerolle, C., Thurig, S., Coles, B. L. K., Ren, J.-C., van der Kooy, D., and Wallace, V. A. 2007. Ciliary margin transdifferentiation from neural retina is controlled by canonical Wnt signaling. Dev Biol 308:54-67.
Dakubo, G.D., Mazerolle, C., Furimsky, M., St. Jacques, B., McMahon, A.P. and Wallace, V.A. 2008. Ihh signaling from endothelial cells is required for sclera and retinal pigment epithelium development in the mouse eye Dev Biol 320:242-255.
Dakubo, G., Beug, S. T, Mazerolle, C. J., Thurig, S. and Wallace, V. A. 2008. Control of glial precursor cell development in the mammalian optic nerve by sonic hedgehog from retinal ganglion cells. Brain Research 1228:27-42.
Medina, C. F., Mazerolle M., Wang, Y., Coupland, S., Gibbons, R. J., Wallace, V. A and D. J. Picketts. 2008. Altered visual function and interneuron survival in Atrx knockout mice: Inference for the human syndrome. Hum Molecular Genetics 18(5):966-77.
Wall, D. S., McNeill, B., Mazerolle, C., Thurig, S., Wang, Y., Kageyama, R. and V. A. Wallace. 2009. Progenitor cell proliferation in the retina is dependent on Notch-independent Sonic Hedgehog/Hesl Activity J Cell Biol 184(1):101-12.
Laboratory Members
Research Associate
Dr. Ya Ping Wang - ypwang@ottawahospital.on.ca
Graduate Students
Charles Campbell - charcampbell@ohri.ca
Randy Ringuette - rringuette@ohri.ca
Andrew Ha - andha@ohri.ca
Brian McNeill - bmcneill@ohri.ca
Technicians
Chantal Mazerolle - cmazerolle@ohri.ca
Sherry Thurig - sthurig@ohri.ca
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