DPhil (OXON)
Professor, Department of Medical Genetics, Faculty of Medicine, UBC
Principal Investigator, Centre for Blood Research, Vancouver Prostate Centre and Michael Smith Laboratories
Full Member
Our results support a “Vascular hypothesis of AD” and demonstrate that amyloidogenesis triggers BBB disruption and leakiness through promoting neoangiogenesis and hypervascularity. We demonstrate that immunization with Amyloid-beta restores the BBB in AD. Ujiie et al., Jefferies, WA. (2003) Blood-brain barrier permeability precedes senile plaques in an Alzheimer’s disease model. Microcirculation10, 463- 470. Dickstein et al., (2006) Amyloidbeta immunization restore blood-brain barrier integrity in Alzheimer’s disease. FASEB J. 20(3): 426-33. Biron et al. (2011) Amyloidogenesis Triggers Extensive Cerebral Angiogenesis Causing Hypervascularization and Blood-Brain Barrier Permeability in Alzheimer’s Disease. PLoS ONE 6(8): e23789. Biron et al., (2013) Cessation of Neoangiogenesis in Alzheimer’s Disease Follows Amyloid-beta Immunization. Nature Scientific Reports 3:1354; Singh et al., (2021) Reversing pathology in a preclinical model of Alzheimer’s disease by hacking cerebrovascular neoangiogenesis with advanced cancer
therapeutics EbioMed (Lancet) in press Sept 2) Discovered that the Transferrin receptor is expressed on non-dividing endothelial cells where it functions in iron acquisition by the brain and that injected antibodies would target the brain and have utility for delivery of drugs across the blood-brain barrier for the treatment of neurological diseases. Jefferies, et al. (1984) Transferrin receptor on the endothelium of brain capillaries. Nature 312: 162- 163. 3) Discovered the first non-transferrin iron transport system in mammals that shuttles iron from the blood into the brains and its use as a carrier for treating
diseases of the brain. Food et al., (1994) Transport and expression in human melanomas of a transferrin-like GPI-anchored protein. J. Biol. Chem. 269: 3034-3040; Kennard et al., (1995) A novel iron uptake mechanism mediated by GPI-anchored human p97; EMBO Journal 14: 4178-4186; Karkan et al., (2008) A unique carrier for delivery of therapeutic compounds beyond the blood-brain barrier. PLoS ONE. 25;3(6):e2469; Singh et al., (2021) Discovery of a Highly Conserved Peptide in the Iron Transporter Melanotransferrin that Traverses an Intact Blood-Brain Barrier and Localizes in Neural Cells. Frontiers in Neurosciences 15:596976; Eyford et al., (2021) A Nanomule Peptide Carrier Delivers siRNA Across the Intact Blood-Brain Barrier to Attenuate Ischemic Stroke. Frontier in Molecular Biosciences 8:611367)