Wilfred Jefferies

Degrees / Credentials

DPhil (OXON)

Titles

Professor, Department of Medical Genetics, Faculty of Medicine, UBC

Principal Investigator, Centre for Blood Research, Vancouver Prostate Centre and Michael Smith Laboratories

Membership

Full Member

Contact Info

Phone
604-827-5167
Assistant
Cheryl Pfeifer
Assistant Email
Assistant Phone
604-822-9002
Lab Manager
Cheryl Pfeifer
Lab Phone
604-822-2006

Research Information

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)

Publications