Fumio Takei

Professor

Relevant Degree Programs

 

Graduate Student Supervision

Doctoral Student Supervision (Jan 2008 - Mar 2019)
Natural helper celll development and their role in mediating the innate Th2 inflammatory response (2013)

No abstract available.

B cells as regulators of natural killer IFN-gamma production in mice (2011)

No abstract available.

The role of talin in LFA-1 function in cell-mediated cytotoxicity (2010)

No abstract available.

Master's Student Supervision (2010-2017)
Common lymphoid progenitor-independent pathways of innate and T lymphocyte development (2015)

All lymphocytes are thought to develop from a single population of committed lymphoid progenitors termed common lymphoid progenitors (CLPs). However, upstream progenitors termed lymphoid-primed multi-potent progenitors (LMPPs) are known to be more efficient than CLPs in differentiating into T cells and group 2 innate lymphoid cells (ILC2s), suggesting alternative pathways of their development. Here, we have divided LMPPs into CD127- (LMPP-s) and CD127+ (LMPP+s) subsets and compared them with CLPs. Adult LMPP+s are the most efficient progenitors for T cells and ILCs in transplantation assays, and lineage tracking by the recombinase expression also suggests that most ILC2s and NK cells develop from LMPPs independent of CLPs. In the neonatal period CLPs are rare and, unlike prominent neonatal LMPP+s, incapable of differentiating into ILC2s and T cells while their development is highly active. These results suggest non-linear pathways of innate and T lymphocyte development from LMPP+s with limited CLP contributions.

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A more efficient killing machine : how CpG-oligodeoxynucleotides enhance natural killer cell cytokine production and cytotoxicity against leukemia initiating cells (2012)

Natural killer (NK) cells are lymphocytes that comprise part of the innate immune system and play a key role in the early defence against pathogenic organisms and cancer. CpG oligodeoxynucelotides (ODNs) are short synthetic ODN containing unmethylated CpG dinucleotide motifs that have immune-enhancing effects. NK cell-derived IFN-γ is essential for the effects of CpG ODNs, but how NK cells become activated by CpG ODNs remains unclear. We found that CpG ODN-mediated stimulation of NK cells requires IL-12 or IL-18. CpG ODNs did not stimulate IL-12-deficient mouse spleen cells and IL-12 neutralization almost completely inhibited IFN-γ production. Although IL-18 was undetectable in cultures, neutralization significantly dampened the IFN-γ response and addition of exogenous IL-18 greatly enhanced CpG ODN-mediated NK cell stimulation. IL-12 is mainly produced by Gr-1⁺ monocytes and neutrophils, while what cells produce IL-18 remains unknown. We then tested the anti-leukemia effects of CpG ODN-stimulated NK cells. Studies with human acute myeloid leukemia (AML) patients have shown that haploidentical NK cells effectively kill AML blasts, but their ability to lyse leukemia initiating cells (LICs) has not been studied. Therefore, we tested NK cells from haploidentical F1 mice against the mouse AML cell line MN1. F1 mouse NK cells expanded in cultures in the presence of IL-15 and stimulated by CpG ODNs plus IL-18, effectively killed bulk MN1 cells in vitro and reduced the numbers of in vitro colony forming cells. NK cell-treated MN1 cells were also injected into irradiated B6 mice to test whether AML LICs were also killed. F1 mouse NK cells seemed to kill some AML initiating cells since mice receiving NK-treated MN1 cells survived significantly longer than those given untreated MN1 cells, but the frequency of LICs did not significantly differ between MN1 cells incubated with or without NK cells. For NK cells to be used as a treatment for AML, we must find a way to induce a higher cytotoxicity in NK cells or to target them specifically towards LIC.

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Recent Tri-Agency Grants

The following is a selection of grants for which the faculty member was principal investigator or co-investigator. Currently, the list only covers Canadian Tri-Agency grants from years 2013/14-2016/17 and excludes grants from any other agencies.

  • Gender differences in innate lymphoid cells - Canadian Institutes of Health Research (CIHR) - Catalyst Grant (2016/2017)
  • Immunological memory of innate lymphoid and allergic lung inflammation - Canadian Institutes of Health Research (CIHR) - CIHR Fellowship (2015/2016)
  • Development of simple methods to isolate group 2 innate lymphoid cells - Mathematics of Information Technology and Complex Systems (MITACS) - Networks of Centres of Excellence (NCE) - Internship Funds (2014/2015)
  • Innate lymphocyte development - Canadian Institutes of Health Research (CIHR) - Operating Grant (2013/2014)
  • Natural helper cells - Canadian Institutes of Health Research (CIHR) - Operating Grant (2013/2014)
 
 

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