Scientist profiles S-Z

Administrative Assistant: Louise Tucker
Phone: 416 480-4998
Email: louise.tucker@sunnybrook.ca

Education:

• MD, 1980, medicine, University of Toronto, Canada
• FRCPC, 1980, Royal College of Physicians and Surgeons of Canada

Appointments and Affiliations:

• Senior scientist, Biological Sciences, Odette Cancer Research Program, Sunnybrook Research Institute
• Professor, radiation oncology, and medical biophysics, Institute of Medical Sciences, U of T
• Vice-chair, radiation oncology, U of T

Research Focus:

• Cellular and molecular responses of the central nervous system
• Experimental neuroprotective therapeutics

Research Summary:

Radiation injury of the central nervous system (CNS) has devastating and often fatal clinical consequences, and severely limits the dose of radiotherapy that can be delivered to tumours in the brain, head and neck, and lungs. Dr. Wong’s research aims to determine the mechanisms of radiation injury in the CNS and to develop neuroprotective strategies against damage.

The pathogenesis of radiation damage in the CNS remains unknown. Vascular endothelial cells, oligodendrocytes and neural progenitors are believed to be major target cells of CNS radiation injury. A dynamic process of radiation-induced death of target cells, and subsequent secondary injury, is believed to lead to cell loss, tissue damage and functional deficits.

Dr. Wong’s team is studying these effects at the tissue, cellular and molecular levels, focusing on the role of oligodendrocytes, neural progenitor and stem cells, and vascular endothelial cells. Specifically, he is interested in the signaling pathways that mediate radiation-induced apoptosis in the CNS, and the downstream events following apoptosis. He is examining the fate of the different neural cells and progenitor cells, and changes in myelination, protein and gene expression after radiation.

Dr. Wong is also interested in the mechanisms of radiation-induced blood-brain barrier disruption. The research aims to determine the role of growth factors and other proteins in mediating blood-brain barrier disruption and the role of hypoxia and ischemia in signaling the permeability damage response. The CNS has very limited capacity of self-repair, and there is interest in cell-replacement therapy for CNS disorders and injuries.

With a large body of literature on the fundamental properties of neural stem cells and progenitor cells, there is also experimental data to suggest that following transplantation into the CNS, these cells can survive, proliferate, migrate and differentiate, and may contribute to the recovery of neurological deficits. One of Dr. Wong’s experimental therapeutic strategies focuses on the radiation responses of neural stem cells and progenitor cells, and the potential of transplantation of neural stem cells or progenitors as a novel neuroprotective therapy. Another therapeutic strategy is investigating the role of growth factors to alter the injury pathway.

Dr. Wong’s studies are performed in preclinical models and cells cultured from the CNS of these models. Results from this research will enable him to understand better the fundamental mechanisms of CNS radiation injury and to develop effective neuroprotective strategies.

Selected Publications:

See current publications list at PubMed.

1. Cheng Z, Zheng YZ, Li YQ, Wong CS. Cellular senescence in mouse hippocampus after irradiation and the role of p53 and p21. J Neuropath Exp Neurol. 2017;76:260–269.
2. Li YQ, Cheng ZWC, Liu SK, Aubert I, Wong CS. p53 regulates disruption of neuronal development in the adult hippocampus after irradiation. Cell Death Discov. 2016;2:e16072.
3. Cheng Z, Li YQ, Wong CS. Effects of aging on hippocampal neurogenesis after irradiation. Int J Radiat Oncol Biol Phys. 2016;94:1181–1189.
4. Lu F, Li YQ, Aubert I, Wong CS. Endothelial cells regulate p53-dependent apoptosis of neural progenitors after irradiation. Cell Death Dis. 2012 June 21;3:e324.
5. Nordal RA, Nagy A, Pintilie M, Wong CS. Hypoxia and hypoxia-inducible Factor-1 target genes in central nervous system radiation injury: A role for vascular endothelial growth factor. Clin Cancer Res. 2004;10:3342–3353, 2004.
6. Li YQ, Ballinger JR, Nordal RA, Su ZF, Wong CS. Hypoxia in radiation-induced blood-spinal cord barrier breakdown. Cancer Res. 2001;61:3348–3354.

Related News and Stories:

• Funding promising research: Canadian Cancer Society grants six SRI scientists awards for new treatment, detection and quality of life research (Oct. 28, 2005)

Related Links:

• U of T profile, department of medical biophysics