About

Dr. Fumio Takei,  PhD
Senior Scientist

• 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)

 

Research Interest

• Molecular immunology of lymphocyte surface molecules
• Cell-cell interactions
• Molecular Immunology

Our research is concerned with lymphocyte surface molecules that play important roles in the immune system.

We currently study two groups of molecules. The first group of molecules is the Ly-49 family of natural killer (NK) cell receptors. NK cells are capable of killing a wide range of tumor cells and virus-infected cells, but spare normal cells. The precise mechanisms by which NK cells distinguish tumor cells from normal cells and kill the former are still unknown. Recent studies have shown that the Ly-49 family of receptors on NK cells interact with the Major Histocompatibility Complex (MHC) molecules on target cells and inhibit NK cell cytotoxicity, providing protection of normal cells expressing MHC molecules from NK cells.

Through gene cloning studies, we have demonstrated that Ly-49 is encoded by a highly polymorphic gene complex. We have also determined the ligand binding specificities and functions of some of the Ly-49 family members. We are currently investigating the molecular interaction between Ly-49 and MHC, and will further determine the role of Ly-49 in NK cell functions. These studies will help us understand how NK cells kill tumor cells but not normal cells.

The second group of molecules of our interest are cell adhesion molecules ICAMs and LFA-1. These molecules are expressed on the surface of lymphocytes and other cell types. They interact with each other and mediate direct cell-cell binding. These cell adhesion molecules are directly involved in the migration of lymphoid cells into inflamed tissues. They also mediate appropriate cellular interactions that are required for the activation of resting lymphocytes as well as effector functions of activated lymphocytes. The expression and functions of these cell adhesion molecules are strictly regulated, allowing lymphocytes to adhere to other cells only when it is needed.

Our goal is to elucidate the mechanisms that regulate the functions of these molecules. By introducing modified cDNA encoding these adhesion molecules into target cells, as well as by generating recombinant adhesion molecules, we are identifying genes and proteins involved in the regulation of these molecules. Our understanding of the regulation of these cell adhesion molecules will have important implications to the treatment of various immunological and inflammatory diseases.

 

Publications

Selected Publications 

2009

Alcon VL, Luther C, Balce D & Takei F. B cell co-receptor CD72 is expressed on NK cells and inhibits IFN-g production but not cytotoxicity.  Eur J Immunol 39: 826-832, 2009. View Abstract

Haddad EA, Senger LK & Takei F. An accessory role for B cells in the IL-12 induced activation of resting mouse NK cells.  J Immunol 183: 3608-3615, 2009. View Abstract

Mace E, Monkley SJ, Critchley DR & Takei F. A dual role for talin in NK cell cytotoxicity: acitviation of LFA-1 mediated cell adhesion and polarization of NK cells.  J Immunol 182: 948-956, 2009. View Abstract

2008

Veinotte LL, Halim TYF & Takei F. Unique subset of natural killer cells develops from progenitors in lymph node. Blood 111: 4201-4208, 2008. View Abstract

Mace EM, MacLeod MA, Marwali MZ, Dreolini L & Takei F. LFA-1 binding to ligand induces talin-mediated reorganization of the actin cytoskeleton in cytotoxic T cells.  Open Immunol J 1: 51-61, 2008.

2007

Wilson EB, Parachoniak CA, Carpenito C, Mager DL, & Takei F. Expression of murine killer immunoglobulin-like receptor KIRL1 on CD1d-independent NK1.1(+) T cells. Immunogenetics 59 (8): 641-51, 2007. View Abstract

Tabatabaei-Zavareh N, Vlasova A, Greenwood CP, & Takei F. Characterization of developmental pathway of natural killer cells from embryonic stem cells in vitro. PLoS ONE 2 (2): e232, 2007. View Abstract

2006

Veinotte LL, Greenwood CP, Mohammadi N, Parachoniak CA, & Takei F. Expression of rearranged TCRgamma genes in natural killer cells suggests a minor thymus-dependent pathway of lineage commitment. Blood 107 (7): 2673-9, 2006. View Abstract

2005

Maeda M, Carpenito C, Russell RC, Dasanjh J, Veinotte LL, Ohta H, Yamamura T, Tan R, & Takei F. Murine CD160, Ig-like receptor on NK cells and NKT cells, recognizes classical and nonclassical MHC class I and regulates NK cell activation. J Immunol 175 (7): 4426-32, 2005. View Abstract

2004

Marwali MR, MacLeod MA, Muzia DN, & Takei F. Lipid rafts mediate association of LFA-1 and CD3 and formation of the immunological synapse of CTL. J Immunol 173 (5): 2960-7, 2004. View Abstract

Maeda M, Shadeo A, MacFadyen AM, & Takei F. CD1d-independent NKT cells in beta 2-microglobulin-deficient mice have hybrid phenotype and function of NK and T cells. J Immunol 172 (10): 6115-22, 2004. View Abstract

2003

Marwali MR, Rey-Ladino J, Dreolini L, Shaw D, & Takei F. Membrane cholesterol regulates LFA-1 function and lipid raft heterogeneity. Blood 102 (1): 215-22, 2003. View Abstract

2002

Lian RH, Maeda M, Lohwasser S, Delcommenne M, Nakano T, Vance RE, Raulet DH, & Takei F. Orderly and nonstochastic acquisition of CD94/NKG2 receptors by developing NK cells derived from embryonic stem cells in vitro. J Immunol 168 (10): 4980-7, 2002.View Abstract

2001

Maeda M, Lohwasser S, Yamamura T, & Takei F. Regulation of NKT cells by Ly49: analysis of primary NKT cells and generation of NKT cell line. J Immunol 167 (8): 4180-6, 2001. View Abstract

Takei F, McQueen KL, Maeda M, Wilhelm BT, Lohwasser S, Lian RH, & Mager DL. Ly49 and CD94/NKG2: developmentally regulated expression and evolution. Immunol Rev 181: 90-103, 2001. View Abstract

2000

Williams NS, Kubota A, Bennett M, Kumar V, & Takei F. Clonal analysis of NK cell development from bone marrow progenitors in vitro: orderly acquisition of receptor gene expression. Eur J Immunol 30 (7): 2074-82, 2000. View Abstract

1999

Kubota A, Lian RH, Lohwasser S, Salcedo M, & Takei F. IFN-gamma production and cytotoxicity of IL-2-activated murine NK cells are differentially regulated by MHC class I molecules. J Immunol 163 (12): 6488-93, 1999. View Abstract

Kubota A, Kubota S, Lohwasser S, Mager DL, & Takei F. Diversity of NK cell receptor repertoire in adult and neonatal mice. J Immunol 163 (1): 212-6, 1999. View Abstract

Lian RH, Li Y, Kubota S, Mager DL, & Takei F. Recognition of class I MHC by NK receptor Ly-49C: identification of critical residues. J Immunol 162 (12): 7271-6, 1999. View Abstract

Rey-Ladino JA, Huber M, Liu L, Damen JE, Krystal G, & Takei F. The SH2-containing inositol-5’-phosphatase enhances LFA-1-mediated cell adhesion and defines two signaling pathways for LFA-1 activation. J Immunol 162 (10): 5792-9, 1999. View Abstract

1998

Rey-Ladino JA, Pyszniak AM, & Takei F. Dominant-negative effect of the lymphocyte function-associated antigen-1 beta (CD18) cytoplasmic domain on leukocyte adhesion to ICAM-1 and fibronectin. J Immunol 160 (7): 3494-501, 1998. View Abstract

1997

Takei F, Brennan J, & Mager DL. The Ly-49 family: genes, proteins and recognition of class I MHC. Immunol Rev 155: 67-77, 1997. View Abstract

1996

Brennan J, Lemieux S, Freeman JD, Mager DL, & Takei F. Heterogeneity among Ly-49C natural killer (NK) cells: characterization of highly related receptors with differing functions and expression patterns. J Exp Med 184 (6): 2085-90, 1996. View Abstract

Brennan J, Mahon G, Mager DL, Jefferies WA, & Takei F. Recognition of class I major histocompatibility complex molecules by Ly-49: specificities and domain interactions. J Exp Med 183 (4): 1553-9, 1996. View Abstract

1994

Brennan J, Mager D, Jefferies W, & Takei F. Expression of different members of the Ly-49 gene family defines distinct natural killer cell subsets and cell adhesion properties. J Exp Med 180 (6): 2287-95, 1994. View Abstract

1989

Horley KJ, Carpenito C, Baker B, & Takei F. Molecular cloning of murine intercellular adhesion molecule (ICAM-1). Embo J 8 (10): 2889-96, 1989. View Abstract

Lab People

Postdoctoral Fellow

Graduate Students Evette Haddad Tim Halim Emily Mace Laura Guillon (nee Senger) Valeria Rytova Kathrin Warner

Other members

Open Positions

September 1, 2008: We are currently accepting post-doctoral and graduate student applications.