Academic Rank:
Professor, UBC
Distinguished Scientist, Terry Fox Laboratory
Affiliation(s):
Short Bio:
  • Professor, Pathology & Laboratory Medicine, University of British Columbia (UBC)
  • Associate Member, Medical Genetics, University of British Columbia (UBC)
  • Associate Member, Microbiology, University of British Columbia (UBC)

Academic background

  • BSc, University of Tokyo, Tokyo, Japan, Biochemistry. 1968
  • PhD, University of British Columbia, Vancouver, BC, Immunology. 1976
  • Postdoctoral Fellow, University of British Columbia, Microbiology, 1977
  • Postdoctoral Fellow, MRC Laboratory of Molecular Biology, Cambridge, England. 1979

Research Interest

Natural killer (NK) cells have two major functions, namely killing of tumor cells and production of cytokines, in particular interferon-g. These functions of NK cells are triggered by cell surface receptors that recognize ligands on tumor cells or cytokines. NK cells also express inhibitory receptors that recognize MHC class I on normal cells. A balance between stimulatory and inhibitory receptors mediates anti-tumor NK cell functions and tolerance to normal cells. In our laboratory, we are studying how NK cells acquire those stimulatory and inhibitory receptors as well as their functions during their development and how the process of tumor cell killing is regulated. These studies will likely lead to new ways to enhance anti-tumor functions of NK cells without affecting self-tolerance.

It is generally thought that NK cells develop from hematopoietic stem cells in the bone marrow and migrate to various tissues. However, we have recently found NK cell progenitors in the lymph node and lung and suggested the presence of multiple pathways of NK cell development, which may explain why NK cells in various tissues differ from each other in phenotype and function. We are currently studying the relationship between the NK cell progenitors we have identified and other lymphoid progenitors. We are also investigating the mechanisms by which NK cells acquire their functions during development.

Killing of tumor cells by NK cells is a multi-step process, namely initial binding to target, subsequent polarization of NK cells and finally polarization and exocytosis of lytic granules. We have shown that the cell adhesion molecule LFA-1 not only mediates binding of NK cells to target cells but also acts as a stimulatory receptor and induces actin polarization in NK cell. By studying NK cells generated in vitro from mutant ES cells, we have shown that the cytoplasmic protein talin is critical for LFA-1-mediated actin polarization. We are currently studying the mechanisms that regulate polarization of lytic granules, how inhibitory receptors inhibit the killing process and why the process is impaired in NK cells that develop in MHC class I-deficient mice.

NK cells stimulated by cytokines such as IL-12 and IL-18 or toll-like receptor ligands such as CpG-oligodeoxynucleotides produce large amounts of interferon-g. We have recently found that B cells unexpectedly regulate the stimulation of NK cells by IL-12 and CpG-oligodeoxynucleotides. As they are often used as adjuvant to enhance anti-tumor immunity, we are currently exploring ways to enhance NK cell functions by controlling B cell-mediated regulatory mechanisms.