Dr. Wilfred A. Jefferies earned his Doctor of Philosophy degree from the Sir William Dunn School of Pathology at the University of Oxford for studies on glycoproteins expressed on activated lymphocytes. His discoveries include identifying the OX40 (CD134) co-stimulatory immune checkpoint molecule expressed on activated CD4 cells. He defined transferrin receptors (OX26/CD71) in the Blood-Brain Barrier and characterized diseases of the central nervous system in which hypervascularity occurs. From these observations, Dr. Jefferies created the p97/melanotransferrin “Trojan Horse” for delivering therapeutics to the brain for the treatment of brain tumours. Further work includes elucidating immune subversion mechanisms in viruses and tumours, along with methods to overcome these conditions, and characterizing the epigenetic regulation of antigen processing in cancer cells. Dr. Jefferies’ research group recently discovered the CD74-dependent Major Histocompatibility Complex-I (MHC-I or HLA) and the MHC-I recycling intracellular pathways underpinning cross-presentation in dendritic cells, both of which are critical for priming MHC-I restricted immune responses against viruses and tumours. Finally, his group has recently identified two important classes of calcium channels that function to limit inappropriate immune responses, leading to pathology in autoimmune disease and possibly cancer.
Dr. Jefferies’ current research program focuses on discovering and translating new therapies for disease. His current interests are in tumour immunology and cancer immunotherapy; antigen presentation and vaccines; and blood-brain barrier and angiogenesis. His work on cancer targets the restoration of the immune system’s ability to recognize tumours that have lost functional antigen processing machinery components, which may render selected tumours “invisible” to adaptive immune responses. His team is also utilizing novel screening systems to identify genes, proteins and small molecules that are able to restore and enhance immune recognition and killing of cancer cells. Notably, with other Vancouver Prostate Centre colleagues, Dr. Jefferies is leading an initiative to examine the use of IL-33 as an immune-biomarker for metastatic prostate tumours and a prognosticator for recurrence of prostate cancer in patients.
Dr. Jefferies has more than 100 publications, holds 60 patents, and has supervised 42 graduate students, 17 postdoctoral fellows and over 100 undergraduate research projects. His research discoveries have created the intellectual foundation for four University spin-out companies, representing a critical avenue for knowledge translation resulting in hundreds of full-time high technology positions. Overall, Dr. Jefferies’
research continues to contribute to understanding how immune responses are initiated and expanded, how tumours and infectious pathogens subvert these processes, and how autoimmunity results from dysregulation of the immune response.
2016 Discovery of a metastatic immune escape mechanism initiated by the loss of expression of the tumour biomarker interleukin-33. I Saranchova, et al., Scientific reports 6, 30555
2014 The ion channel TRPV1 regulates the activation and pro inflammatory properties of CD4+ T cells. S Bertin, et al., Nature immunology 15 (11),
2012 A CD74-dependent MHC class I endolysosomal cross-presentation pathway. G Basha, et al., Nature immunology 13 (3), 237-245
2008 Epigenetic enhancement of antigen processing and presentation promotes immune recognition of tumors. AF Setiadi, et al., Cancer Research
68 (23), 9601-9607
2008 MHC class I endosomal and lysosomal trafficking coincides with exogenous antigen loading in dendritic cells. G Basha, et al., PloS one 3 (9), e3247
2007 TAP expression reduces IL‐10 expressing tumor infiltrating lymphocytes and restores immunosurveillance against melanoma. QJ Zhang, et al., International journal of cancer 120 (9), 1935-1941
2005 Restoration of the expression of transporters associated with antigen processing in lung carcinoma increases tumor-specific immune responses and survival. Y Lou, et al., Cancer Research 65 (17), 7926-7933
2003 Blood–brain barrier permeability precedes senile plaque formation in an Alzheimer disease model. M Ujiie, et al., Microcirculation 10 (6),
2003 Control of dendritic cell cross-presentation by the major histocompatibility complex class I cytoplasmic domain. G Lizée, et al., Nature immunology 4 (11), 1065
2003 Identification and functional characterization of voltage-dependent calcium channels in T lymphocytes. MF Kotturi, et al., Journal of Biological Chemistry 278 (47), 46949-46960
2000 TAP expression provides a general method for improving the recognition of malignant cells in vivo. J Alimonti, et al., Nature biotechnology 18 (5), 515
1996 Serum levels of the iron binding protein p97 are elevated in Alzheimer′s disease. ML Kennard, et al., Nature Medicine 2 (11), 1230-1235