Dr. Makoto Yawata, M.D., Ph.D.
Research Assistant Professor
Department of Pediatrics, Yong Loo Lin School of Medicine
We investigate the mechanisms of human natural killer cell responses against particular types of virus infections and cancer.
Human individuals differ substantially in NK cell responses, and genetic diversity in NK cell receptor genes, such as the Killer cell Immunoglobulin-like Receptors (KIR) and their ligands –HLA, are important factors that personalize NK responses. The KIR system has become recognized worldwide as an immunological biomarker to guide donor selection in bone marrow transplant. We provide expertise in KIR genotyping and advice to the transplant teams regionally for this purpose.
We are now in a clinical environment where the use of humanized antibodies is commonplace, for example in cancer treatment. Other forms of new immunomodulatory agents are also being developed. These new clinical options provide opportunities that were, hitherto, not possible. We will use our platform to test new combination therapies which require exquisite understanding of the underlying immunological principles.
We combine human genetics, immunological assays, protein chemistry, and histopathology approaches. Using high-dimensional flow cytometry, we quantify the responses of individual NK cell subsets. We are also developing a primate platform for NK cell research to enable testing of therapeutic compounds and biologics in preclinical trials.
1. Nemat-Gorgani N, Hilton HG, Henn BM, Lin M, Gignoux CR, Myrick JW, Werely CJ, Granka JM, Möller M, Hoal EG, Yawata M, Yawata N, Boelen L, Asquith B, Parham P, Norman PJ (2018) Different Selected Mechanisms Attenuated the Inhibitory Interaction of KIR2DL1 with C2+ HLA-C in Two Indigenous Human Populations in Southern Africa. Journal of Immunology 200(8):2640-2655.
2. Ichise H, Nagano S, Maeda T, Miyazaki M, Miyazaki Y, Kojima H, Yawata N, Yawata M, Tanaka H, Saji H, Masuda K, Kawamoto H (2017) NK cell alloreactivity against KIR-ligand-mismatched HLA-haploidentical tissue derived from HLA haplotype-homozygous iPSCs. Stem Cell Reports 9(3):853-867.
3. Yawata N, Selva KJ, Liu YC, Tan KP, Lee AWL, Siak J, Lan W, Vania M, Arundhati A, Tong L, Li J, Mehta JS, Yawata M (2016) Dynamic change in natural killer cell type in the human ocular mucosa in situ as means of immune evasion by adenovirus infection. Mucosal Immunology 9:159–170.