Shun Wong
Research Synopsis
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.