Wilfred Jefferies

Contact Information
2222 Health Sciences Mall
Vancouver, BC
Canada V6T 1Z3
Tel 1-604-822-6961
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. Basha G, Omilusik K, Chavez-Steenbock A, Reinicke AT, Lack N, Choi KB, Jefferies WA. A CD74-dependent MHC class I endolysosomal cross-presentation pathway. Nat Immunol. 2012 Feb 5;13(3):237-245. doi: 10.1038/ni.2225.

2. Biron KE, Dickstein DL, Gopaul R, Jefferies WA. Amyloid triggers extensive cerebral angiogenesis causing blood brain barrier permeability and hypervascularity in Alzheimer’s disease. PLoS One. 2011;6(8):e23789. Epub 2011 Aug 31.

3. Omilusik K, Priatel JJ, Chen X, Wang YT, Xu H, Choi KB, Gopaul R, McIntyre-Smith A, Teh HS, Tan R, Bech-Hansen NT, Waterfield D, Fedida D, Hunt SV, Jefferies WA. The Ca(v)1.4 calcium channel is a critical regulator of T cell receptor signaling and naive T cell homeostasis. Immunity. 2011 Sep 23;35(3):349-60. Epub 2011 Aug 11.

4. Bennett J, Basivireddy J, Kollar A, Biron KE, Reickmann P, Jackson SC, Jefferies WA, McQuaid S. Blood-brain barrier disruption and enhanced vascular permeability in the multiple sclerosis model EAE. J Neuroimmunol. 2010 Dec 15;229(1-2):180-91.

5. Reinicke AT, Omilusik KD, Basha G, Jefferies WA. Dendritic cell cross-priming is essential for immune responses to Listeria monocytogenes. PLoS One. 2009 Oct 6;4(10):e7210.

6. Setiadi AF, Omilusik K, David MD, Seipp RP, Hartikainen J, Gopaul R, Choi KB, Jefferies WA. Epigenetic enhancement of antigen processing and presentation promotes immune recognition of tumors. Cancer Res. 2008 Dec 1;68(23):9601-7.

7. Basha G, Lizée G, Reinicke AT, Seipp RP, Omilusik KD, Jefferies WA. MHC class I endosomal and lysosomal trafficking coincides with exogenous antigen loading in dendritic cells. PLoS One. 2008 Sep 19;3(9):e3247.

8. Zhang QJ, Li XL, Wang D, Huang XC, Mathis JM, Duan WM, Knight D, Shi R, Glass J, Zhang DQ, Eisenbach L, Jefferies WA. Trogocytosis of MHC-I/peptide complexes derived from tumors and infected cells enhances dendritic cell cross-priming and promotes adaptive T cell responses. PLoS One. 2008 Aug 29;3(8):e3097.

9. Karkan D, Pfeifer C, Vitalis TZ, Arthur G, Ujiie M, Chen Q, Tsai S, Koliatis G, Gabathuler R, Jefferies WA. A unique carrier for delivery of therapeutic compounds beyond the blood-brain barrier. PLoS One. 2008 Jun 25;3(6):e2469.

10. Lou Y, Basha G, Seipp RP, Cai B, Chen SS, Moise AR, Jeffries AP, Gopaul RS, Vitalis TZ, Jefferies WA. Combining the antigen processing components TAP and Tapasin elicits enhanced tumor-free survival. Clin Cancer Res. 2008 Mar 1;14(5):1494-501.

Education

  • Ph.D. University of Oxford UK, 1985

Comments are closed, but trackbacks and pingbacks are open.