Dr. Wilfred Jefferies

Professor, University of British Columbia

Dr. Wilfred Jefferies is a Professor at the University of British Columbia (UBC; Vancouver, BC) and has been conducting research and teaching there for over 27 years.  He originally obtained a B.Sc. from the University of Victoria (Victoria, BC) and then moved to Oxford University (Oxford, UK) where he obtained a Doctor of Philosophy in Molecular Pathology and Immunology under Dr. Alan Williams.  From there, he studied with Dr. Sune Kvist  at the Institut Suisse de Recherches Expérimentales sur le Cancer (Lausanne, Switzerland) and later at the Ludwig Institute for Cancer Research, Karolinska Institute (Stockholm, Sweden).  Dr. Jefferies joined the Michael Smith Laboratories (formerly The Biotechnology Laboratory) at UBC, and is also a member of the Departments of Microbiology & Immunology, Medical Genetics, and Zoology, as well as the Centre for Blood Research and the Djavad Mowafaghian Centre for Brain Health.

Research on the blood-brain barrier remains an active area of research in Dr. Jefferies’ laboratory.  Recently, his group demonstrated that this barrier is impaired in Alzheimer’s disease prior to disease onset and the appearance of plaques in the brain.  He was awarded the Wiederhelm Award prize for this research published in Microcirculation with the follow-up paper published in FASEB Journal. Dr. Jefferies and his group recently extended these studies. Evidence of reduced BBB integrity preceding other Alzheimer’s disease (AD) pathology has also provided a strong link between cerebrovascular angiopathy and AD. However, the “Vascular hypothesis”, maintains that BBB leakiness in AD is likely due to hypoxia and neuroinflammation leading to vascular deterioration and apoptosis.  Dr. Jefferies and his group recently proposed an alternative hypothesis:  amyloidogenesis promotes extensive neoangiogenesis leading to increased vascular permeability and subsequent hypervascularization in AD.  Studying the cerebrovascular integrity in the Tg2576 AD model mice, Dr. Jefferies and his group examined the expression of tight junction (TJ) proteins, occludin and ZO-1, in conjunction with markers of apoptosis and angiogenesis. In aged Tg2576 AD mice, a significant increase in the incidence of disrupted TJs, compared to age matched wild-type littermates and young mice of both genotypes.  This was directly linked to an increased microvascular density but not apoptosis, which strongly supported amyloidogenic triggered hypervascularity as the basis for BBB disruption. Hypervascularity in human patients was corroborated in a comparison of postmortem brain tissues from AD and controls. These results demonstrated that amylodogenesis mediates BBB disruption and leakiness through promoting neoangiogenesis and hypervascularity, resulting in the redistribution of TJs that maintain the barrier and thus, provides a new paradigm for integrating vascular remodeling with the pathophysiology observed in AD. Dr. Jefferies’ group also highlight the intriguing parallel with the “wet” form of age-related macular degeneration, in which blood vessels forming the blood eye barrier, grow behind the retina and then leak blood and fluid, leading to hemorrhaging, swelling, and formation of scar tissue. This research has since been published in PLoS One.  More recently, Dr. Jefferies’ work has been published in Nature Scientific Reports.  A study which involves the examination of a therapy that modulates angiogenesis showing that it modified disease progression in pre-clinical transgenic animal models of AD.

Dr. Wilfred Jefferies Grants