Wilfred Jefferies

Contact Information
2222 Health Sciences Mall
Vancouver, BC
Canada V6T 1Z3
Tel: 1-604-822-6961
Email: wilf@brc.ubc.ca

Current Positions

  • Professor, Biomedical Research Centre.
  • Professor, Microbiology and Immunology, Science.
  • Professor, Michael Smith Laboratories.

Research Interests

The work in my lab is focused on three cellular processes. First, we are interested in how foreign pathogens are broken down by the cellular degradation machinery and how they are then recognized by the host immune response. We have contributed to characterizing the function of the transporter associated with antigen processing (TAP), which transports peptides into the ER where they assemble with their receptors, the MHC Class I molecules. In the future, we will define the peptide motifs that are effectively transported into the ER by the TAP molecules. We hope to test the hypothesis suggesting that protease components are directly linked to the peptide transport mechanism. Second, we carry out research on Adenovirus (Ad) which processes virulence factors that aid the virus to circumvent the host immune response. In our work on Adenovirus, we have concentrated on characterizing a viral protein E3/19K that acts to inhibit surface expression of MHC Class I molecules and to prevent viral peptides from being recognized by T cells. In addition, we plan to examine the chaperone-like capabilities of Ad proteins and the functions in an animal model of Ad infection. The third area of my research concerns a recently discovered method by which mammalian cells acquire iron. We have demonstrated that a cell surface protein belonging to the transferrin family of molecules, called melanotransferrin or p97, is able to directly bind and transport iron into cells. We have also found that this molecule exists as two distinct forms in humans: one is GPI-linked to the cell surface, and the other is a soluble form. In addition, p97 is uniquely expressed in human brain endothelium, suggesting that it may transport iron across the Blood Brain Barrier (BBB). Furthermore, p97 is expressed on reactive microglia cells uniquely associated with deposits in brains of patients with Alzheimer’s Disease. We have found soluble p97 to be present in elevated concentrations in AD serum and may be a biochemical marker of disease progression and recovery. In the future, we plan to examine the role of p97 in BBB transcytosis. We also plan to determine if GPI-linked p97 can transport metals other than iron.

Publications

  1. Fenninger F, Jefferies WA. What’s Bred in the Bone: Calcium Channels in Lymphocytes. J Immunol. 2019 Feb 15;202(4):1021-1030. doi: 10.4049/jimmunol.1800837. Review.
  2. Williams DE, Gunasekara NW, Ratnaweera PB, Zheng Z, Ellis S, Dada S, Patrick BO, Wijesundera RLC, Nanayakkara CM, Jefferies WA, de Silva ED, Andersen RJ. (2018) Serpulanines A to C, N-Oxidized Tyrosine Derivatives Isolated from the Sri Lankan Fungus Serpula sp.: Structure Elucidation, Synthesis, and Histone Deacetylase Inhibition. Journal of Natural Products. 81(1):78-84. doi: 10.1021/acs.jnatprod.7b00680. [Epub ahead of print] PMID: 29303267.
  3. Thom G, Tian MM, Hatcher JP, Rodrigo N, Burrell M, Gurrell I, Vitaliz TZ, Abraham T, Jefferies WA, Webster CI, Gabathuler R. (2018) A peptide derived from melanotransferrin delivers a protein-based interleukin 1 receptor antagonist across the BBB and ameliorates neuropathic pain in a preclinical model. Journal of Cerebral Blood Flow & Metabolism 0(00): 1-15. doi: 10.1177/0271678X18772998.
  4. Saranchova I, Han J, Zaman R, Arora H, Huang H, Fenninger F, Choi KB, Munro L, Pfeifer C, Welch I, Takei F, Jefferies WA. (2018) Type 2 Innate Lymphocytes Actuate Immunity Against Tumours and Limit Cancer Metastasis. Scientific Reports 8(1):2924. doi: 10.1038/s41598-018-20608-6.
  5. Hur WS, Mazinani N, Lu XJD, Yefet LS, Byrnes JR, Ho L, Yeon JH, Filipenko S, Wolberg AS, Jefferies WA, Kastrup CJ, “Coagulation Factor XIIIa can Crosslink Amyloid β into Dimers and Oligomers and to Blood Proteins”, Journal of Biological Chemistry (SA) (IF 4.1), Epub ahead of print. 2018-11. doi: 10.1074/jbc.RA118.005352.
  6. Arora H, Wilcox SM, Johnson LA, Munro L, Eyford BA, Pfeifer CG, Welch I, Jefferies WA. (2018) ABCF1 protects against lethal septic shock through its novel E2-ubiquitin activity. Immunity in press.
  7. Wilcox SW, Arora H, Munro L, Xin J, Fenninger F, Johnson LA,  Pfeifer CG, Choi KB, Hou J, Hoodless PA, and Jefferies WA. (2017) The Role of the Innate Immune Response Regulatory Gene ABCF1 in Mammalian Embryogenesis and Development.  PLoS ONE 12(5): e0175918.
  8. Saranchova I, Han, J, Huang H, Fenninger F, Choi KB, Munro L, Pfeifer C, Welch I, Wyatt AW, Fazli L, Gleave ME, Jefferies WA.  (2016) Discovery of a metastatic immune escape mechanism initiated by the loss of expression of the tumour biomarker interleukin-33.  Scientific Reports Sep 13; 6:30555 |  DOI: 10.1038/srep30555.
  9. Bertin S, Aoki-Nonaka Y, de Jong PR, Nohara LL, Xu H, Stanwood SR, Srikanth S, Lee J, To K, Abramson L, Yu T, Han T, Touma R, Li X, González-Navajas JM, Herdman S, Corr M, Fu G, Dong H, Gwack Y, Franco A, Jefferies WA*, Raz E*. (2014) The ion channel TRPV1 regulates the activation and proinflammatory properties of CD4(+) T cells. Nature Immunology Nov;15(11):1055-63.

Education

  • Ph.D. University of Oxford UK, 1985.