Our team investigates human natural killer (NK) cell responses in infection and cancer. We are developing two projects in our laboratory.

Project 1 studies human variation in NK cell responses against three viral entities prevalent in Asia: Human papilloma virus (HPV), Epstein Barr virus (EBV), and Hepatitis B virus (HBV). Why are there person-to-person differences in susceptibility to viral infections? What immune factors cause or allow persistent infection? Why are resident NK cells unresponsive to malignant transformed tissue?  We aim to understand immune-related factors involved in the stages from viral infection to solid tumor formation. The goal is to develop approaches to enhance NK cell responses at each stage as new forms of cellular immunotherapy. Our laboratory utilizes a range of research techniques: high-dimensional flow cytometry, quantitative fluorescence microscopy, laser microdissection, tissue engineering, histology, gene expression profiling, SNP genotyping and protein engineering to understand immune-related factors involved in the stages from viral infection to solid tumor formation.

Project 2 investigates the roles of NK cells in improving outcome in hematopoietic stem cell transplant and hematological malignancy treatment. A characteristic of NK cells is their ability to recognize combinations of HLA class I isoforms in the context of self-non-self recognition. This function is of particular importance when NK cells are transferred between human individuals which differ in their HLA class I background. Our laboratory collaborates with doctors and investigators in the Hematology and Oncology Department and the Department of Pediatrics in the National University Health System in Singapore to evaluate the roles of NK cells in transplant immunology.

Project 1
Study on NK cell responses against oncogenic virus infections and subsequent cancers:  Human papilloma virus infection and cervical cancer, Hepatitis B virus infection and hepatocellular carcinoma, Epstein Barr virus infection and lymphoma

Project 2
Investigating roles for NK cells in hematopoietic stem cell transplant and hematological malignancy treatment.

Yawata M, Yawata N. NK cell KIR heterogeneity and evolution. Chapter 6. Natural Killer cells. Elsevier, 2010.

Sharma D, Bastard K, Guethlein LA, Norman PJ, Yawata N, Yawata M, Pando M, Thananchai H, Dong T, Rowland-Jones, S, Brodsky FM, Parham P. Dimorphic motifs in D0 and D1+D2 domains of KIR3DL1 combine to form receptors with high, moderate and no avidity for the complex of a peptide derived from human immunodeficiency virus and HLA-A*2402. Journal of Immunology 2009; 183:4569-4582.

Kulski JK, Shigenari A, Shiina T, Hosomichi K, Yawata M, Inoko H. HLA-A allele associations with viral MER9-LTR nucleotide sequences at two distinct loci within the MHC alpha block. Immunogenetics 2009; 61:257-270.

Yawata M, Yawata N, Draghi M, Partheniou F, Little AM, Parham P. MHC class I-specific inhibitory receptors and their ligands structure diverse human NK cell repertoires toward a balance of missing-self response. Blood 2008; 112:2369-2380.

Moesta AK, Norman PJ, Yawata M, Yawata N, Gleimer M, Parham P. Synergistic polymorphism at two positions distal to the ligand-binding site makes KIR2DL2 a stronger receptor for HLA-C than KIR2DL3. Journal of Immunology 2008; 180:3969-3979.

Abi-Rached L, Dorighi K, Norman PJ, Yawata M, Parham P. Episodes of natural selection shaped the interactions of IgA-Fc with FcaRI and bacterial decoy proteins. Journal of Immunology 2007; 178:7943-7954.

Yawata M, Yawata N, Parham P. Functional significance of KIR and HLA polymorphisms. Transplantation Now 2007; 11-22.

Thananchai H, Gillespie G, Martin M, Bashirova A, Yawata N, Yawata M, Easterbrook P, McVicar DW, Maenaka K, Parham P, Carrington M, Dong T, Rowland-Jones S. Allele-specific and peptide-dependent interactions between KIR3DL1 and HLA-A and -B. Journal of Immunology 2007; 178:33-37.

Yawata M, Yawata N, Draghi M, Little AM, Partheniou F, Parham P. Roles for HLA and KIR polymorphisms in natural killer cell repertoire selection and modulation of effector function. Journal of Experimental Medicine 2006; 203:633-645.

Draghi M, Yawata N, Gleimer M, Yawata M, Valiante NM, Parham P. Single cell analysis of the human NK cell response to missing-self and its inhibition by HLA class I. Blood 2005; 105:2028-2035.

Takahashi T, Yawata M, Raudsepp T, Lear TL, Chowdhary BP, Antczak DF, Kasahara M. Natural killer cell receptors in the horse: evidence for the existence of multiple transcribed LY49 genes. European Journal of Immunology 2004; 34: 773-784.

Yawata M, Yawata N, Abi-Rached L, Parham P. Variation within the human killer cell immunoglobulin-like receptor (KIR) gene family. Critical Reviews in Immunology 2002; 22:463-482.

Yawata M, Yawata N, McQueen KL, Cheng NW, Guethlein LA, Rajalingam R, Shilling HG, Parham P. Predominance of group A KIR haplotypes in Japanese associated with diverse NK cell repertoires of KIR expression. Immunogenetics 2002; 54:543-550.

Yawata M, Murata S, Tanaka K, Ishigatsubo Y, Kasahara M. Nucleotide sequence analysis of the ~35kb segment containing interferon-gamma-inducible mouse proteasome activator genes. Immunogenetics 2001; 53:119-129.

Kasahara M, Yawata M, Suzuki T. The MHC paralogous group: listing of members and a brief overview. Major Histocompatibility Complex; Evolution, Structure, and Function. Springer-Verlag, 2000; 27-44.

Matsunaga K, Yawata M, Tsuji T, Tani K. HLA class II antigens associated with anti-Ki autoantibody positive connective tissue disease in Japanese. Journal of Rheumatology 1998; 25:1446-1447.

Atefeh KHAKPOOR
Research Fellow

SHAO Zhe
Research Fellow

Cecilia CHIA Li Wei
Research Officer

Maggie LIM Mei Kee
Research Officer