Nakamura’s Contribution to Science



Dr. Nakamura’s contribution to the field of human genetics and cancer research is reflected by his publication of more than 1,430 articles (at November, 2016). These articles include: 34 articles in American Journal of Human Genetics, 115 articles in Cancer Research, 6 articles in Lancet, 17 articles in Nature, 2 articles in Nature Cell Biology, 70 articles in Nature Genetics, 4 articles in Nature Communications, 7 articles in The New England Journal of Medicine, 11 articles in Science and one article in Science Translational Medicine. These papers have been cited over 138,000 times in the scientific literature (h-index=166; at the 62nd on the international h-index ranking (


1. Oncoimmunogenomics/Immunopharmacogenomics

Molecular changes in immune cells associated with disease conditions have not been analyzed in depth. It is obvious that our immune system plays a critical role in various biological and pathological conditions, such as infection, autoimmune diseases, drug-induced skin and liver toxicities, food allergy and rejection of transplanted organs. The recent development of cancer immunotherapies clearly demonstrates the importance of host immune cells, particularly drugs modulating the immune checkpoint molecules, in the fight against cancer. However, the molecular mechanisms by which these new therapies kill tumor cells still remain unclear.  In this regard, we have begun to explore the roll of newly-developed tools such as next generation sequencing in the genetic characterization of the immune system, which has been referred to as immunogenomics/ immunopharmacogenomics. This new field has enormous potential to help us better understand the changes/alterations to our immune responses during the course of various disease conditions. Here we report the deep sequencing of T-cell and B-cell receptors that will enable us to capture the molecular contribution of the immune system which we believe plays a critical role in the pathogenesis of disease.


(1) H. Fang, R. Yamaguchi, X. Liu, Y. Daigo, P.Y. Yew, C. Tanikawa, K. Matsuda, S. Imoto, S. Miyano, and Y. Nakamura: Quantitative T cell repertoire analysis by deep cDNA sequencing of T cell receptor a and b chains using next-generation sequencing (NGS). OncoImmunology, DOI: 10.4161/21624011.2014.968467, 2014

(2) X. Liu, G. Venkataraman, J. Lin, K. Kiyotani, S. Smith, M. Montoya, Y. Nakamura, and J. Kline: Highly clonal T cell receptor repertoire among regulatory T cells in follicular lymphoma tissues – correlation with the CD8+ T cell receptor repertoire.  OncoImmunology, DOI:10.1080/2162402X.2014. 1002728, 2015

(3) P.Y. Yew, P.Y. Yew, H. Alachkar, R. Yamaguchi, K. Kiyotani, H. Fang, K.L. Yap, H.T. Liu, A. Wickrema, A. Artz, K. van Besien, S. Imoto, S. Miyano, M.R. Bishop, W. Stock, and Y. Nakamura: Quantitative characterization of T cell repertoire in allogeneic hematopoietic stem cell transplant recipients.  Bone Marrow Transplantation, doi:10.1038/bmt.2015.133, 2015

(4) M. Jang, P.-Y. Yew, K. Hasegawa, Y. Ikeda, K. Fujiwara, G.F. Fleming, Y. Nakamura, and J.-H. Park: Characterization of T cell repertoire of blood, tumor and ascites in ovarian cancer patients using next generation sequencing. OncoImmunology, DOI:10.1080/2162402X.2015.1030561, 2015

(5) N.J. Choudhury, K. Kiyotani, K.L. Yap, A. Campanile, T. Antic, P.Y. Yew, G. Steinberg, J.-H. Park, Y. Nakamura, and P.H. O’Donnell: Low T cell receptor diversity, high somatic mutation burden, and high neoantigen load as predictors of clinical outcome in muscle-invasive bladder cancer. European Urology Focus, doi:10.1016/j.euf.2015.09.007, 2015

(6) N. Choudhury, and Y. Nakamura The importance of immunopharmacogenomics in cancer treatment: Patient selection and monitoring for immune checkpoint antibodies. Cancer Science, DOI: 10.1111/cas.12862, 2016

 (7) K. Tamura, S. Hazama, R. Yamaguchi, S. Imoto, H. Takenouchi, Y. Inoue, S. Kanekiyo, Y. Shindo, S. Miyano, Y. Nakamura, and K. Kiyotani: Characterization of T cell repertoire in tumor tissues and blood in advanced colorectal cancers through deep T cell receptor sequencing. Oncology Letters, 11:3643-3649, 2016

(8) M. Leisegang, B. Engels, K. Schreiber, P.Y. Yew, K. Kiyotani, C. Idel, A. Arina, J. Duraiswamy, R.R. Weichselbaum, W. Uckert, Y. Nakamura and H. Schreiber:  Eradication of large solid tumors by gene therapy with a T cell receptor targeting a single cancerspecific point mutation. Clinical Cancer Research, :DOI: 10.1158/1078-0432.CCR-15-2361, 2016

(9) H. Alachkar and Y. Nakamura: Deep Sequencing of the T-cell receptor repertoire in Patients with haplo-cord and matched-donor transplant (review). Chimerism, DOI:10.1080/19381956. 2015.1128624, 2016

(10) C.G. Chapman, R. Yamaguchi, K. Tamura, J. Weidner, S. Imoto, J Kwon, H Fang, P.-Y. Yew, S.R. Marino, S. Miyano, Y. Nakamura, and K. Kiyotani: Characterization of T-cell receptor repertoire in inflamed tissues of patients with Crohn’s disease through deep sequencing. Immflamatory Bowel Diseases, doi: 10.1097/MIB.0000000000000752, 2016

(11) J.-H. Park, M. Jang, Y.E. Tarhan, T. Katagiri, M. Sasa, Y. Miyoshi, K.R. Kalari, V.J. Suman, R. Weinshilboum, L. Wang,  J.C. Boughey,  M.P. Goetz, and Y. Nakamura: Clonal expansion of anti-tumor T cells in breast cancer correlates with response to neoadjuvant chemotherapy.  International Journal of Oncology,  DOI: 10.3892/ijo.2016.3540, 2016

(12) T. Kimura, S. Fukushima, A. Miyashita, J. Aoi, M. Jinnin, T. Kosaka, M. Matsukawa, H. Inoue, K. Kiyotani, J.-H. Park, Y. Nakamura, and H. Ihn: Myasthenic crisis and polymyositis induced by one dose of nivolumab.  Cancer Science, 107:1055–1058 (doi: 10.1111/cas.12961), 2016

(13) H. Inoue, J.-H. Park, K. Kiyotani, M. Zewde, A. Miyashita, J. Masatoshi, Y. Kiniwa, R. Okuyama, R. Tanaka, Y. Fujisawa, H. Kato, A. Morita, J. Asai, N. Katoh, K. Yokota, M. Akiyama, H. Ihn, S. Fukushima and Y. Nakamura: Intratumoral expression levels of PD-L1, GZMA, and HLA-A associated with oligoclonal T cell expansion predict response to nivolumab in metastatic melanoma. OncoImmunology,, 2016

(14) H. Alachkar, M. Mutonga, T. Kato, S. Kalluri; Y. Kakuta, M, Uemura, R, Imamura, N. Nonomura, V. Vujjini, S. Alasfar, H. Rabb, Y. Nakamura, and N. Alachkar: Quantitative characterization of T-cell repertoire and biomarkers in kidney transplant rejection. BMC Nephrology, in press, 2017

(15) K. Kiyotani, J.-H. Park, H. Inoue, A. Husain, S. Olugbile, M. Zewde, Y. Nakamura, and W.T. Vigneswaran: Integrated analysis of somatic mutations and immune microenvironment in malignant pleural mesothelioma. Oncoimmunology, in press, 2017

(16) H. Alachkar and Y. Nakamura: Deep Sequencing of the T-cell receptor repertoire in Patients with haplo-cord and matched-donor transplant (review). Chimerism, DOI:10.1080/19381956. 2015.1128624, 2016

(17) K. Kiyotani, T.H. Mai and Y. Nakamura: Comparison of exome-based HLA class I genotyping tools: identification of platform-specific genotyping errors. Journal of Human Genetics, :doi:10.1038/jhg.2016.141, 2016

(18) H. Alachkar, M. Mutonga, T. Kato, S. Kalluri; Y. Kakuta, M, Uemura, R, Imamura, N. Nonomura, V. Vujjini, S. Alasfar, H. Rabb, Y. Nakamura, and N. Alachkar: Quantitative characterization of T-cell repertoire and biomarkers in kidney transplant rejection. BMC Nephrology, 17DOI: 10.1186/s12882-016-0395-3, 2016

(19) T.H. Mai, A. Takano, H. Suzuki, T. Hirose, T. Mori, K. Teramoto, K. Kiyotani, Y. Nakamura, and Y. Daigo: Quantitative analysis and clonal characterization of T-cell receptor beta repertoires in advanced non-small cell lung cancer patients treated with cancer vaccine treatment. Oncology Letters, in press, 2017

(20) K. Kiyotani, J.-H. Park, H. Inoue, A. Husain, S. Olugbile, M. Zewde, Y. Nakamura, and W.T. Vigneswaran: Integrated analysis of somatic mutations and immune microenvironment in malignant pleural mesothelioma. Oncoimmunology,, 2017

(21) Y. Ikeda, K. Kiyotani, P.Y. Yew, S. Sato, Y. Imai, R. Yamaguchi, S. Miyano, K. Fujiwara, K. Hasegawa, and Y. Nakamura: Clinical significance of T cell clonality and expression levels of immune-related genes in endometrial cancer. Oncology Reports, in press, 2017

(22) V. Saloura, A. Fatima, M. Zewde, K. Kiyotani, R. Brisson, J.-H. Park, Y. Ikeda, T. Vougiouklakis, T. Seiwert, N. Cipriani, M. Lingen, E. Vokes, and Y. Nakamura: Characterization of the T-cell receptor repertoire in patients with locoregionally advanced squamous cell carcinoma of the head and neck. Clinical Cancer Research, in press, 2017

(23) T. Kato, T. Iwasaki, M. Uemura, A. Nagahara, H. Higashihara, K. Osuga, Y. Ikeda, K. Kiyotani, J.-H. Park, N. Nonomura and Y. Nakamura: Characterization of the cryoablation-induced immune response in kidney cancer. OncoImmunology, in press, 2017

(24) T. Kato, J.-H. Park, K. Kiyotani, Y. Ikeda, Y. Miyoshi and Y. Nakamura: Integrated analysis of somatic mutations and immune microenvironment of multiple regions in breast cancers. Oncotarget, in press, 2017


2. Characterization of genes involved in human cancer (p53 and its target genes, kinases and protein methyltransferases)


Dr. Nakamura group reported dozens of genes playing key roles in many types of human cancer through extensive expression profile analysis and subsequent functional analysis of gene products. An example of a group of genes involved in development and progression of human cancer is the protein methyltransferases including SMYD3 and SUV39H2.  His group is a pioneer in non-histone protein methyltransferases as summarized in Nature Reviews Cancer (2015). In addition, his group has reported on many genes that are involved in the p53 pathway such as BAI1, p53R2, p53AIP1, p53DINP1, p53RDL, and PADI4. These genes play critical roles in p53-dependent DNA repair, angiogenesis, protein modification, and apoptosis. Furthermore, his group also reported a number of genes involved in the b-catenin-TCF pathway including the first mutation detection in the AXIN1 gene.  


(1) Y. Miyoshi,  K. Iwao, Y. Nagasawa, T. Aihara, Y. Sasaki, S. Imaoka, M. Murata, T. Shimano, and Y. Nakamura: Activation of the beta-catenin gene in primary hepatocellular carcinomas by somatic alterations involving exon 3. Cancer Research, 58:2524-2527, 1998 (480 citations)

(2) S. Satoh, Y. Daigo, Y. Furukawa, T. Katoh, N. Miwa, T. Nishiwaki, T. Kawasoe, H. Ishiguro, M. Fujita, T. Tokino, Y. Sasaki, S. Imaoka, M. Murata, T. Shimano, Y. Yamaoka, and Y. Nakamura: AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1. Nature Genetics, 24:245-250, 2000 (881 citations)

(3) K. Oda, H. Arakawa, T. Tanaka, K. Matsuda, C. Tanikawa, T. Mori, H. Nishimori, K. Tamai, T. Tokino, Y. Nakamura, and Y. Taya: p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53. Cell, 102:849-862, 2000 (1106 citations)

(4) H. Tanaka, H. Arakawa, T. Yamaguchi, K. Shiraishi, S. Fukuda, K. Matsui, Y. Takei, and Y. Nakamura: A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint DNA damage. Nature, 404:42-49, 2000 (762 citations)

(5) H. Okabe, S. Satoh, T. Kato, O. Kitahara, R. Yanagawa, Y. Yamaoka, T. Tsunoda, Y. Furukawa and Y. Nakamura: Genome-wide analysis of gene expression in human hepatocellular carcinomas using cDNA microarray: identification of genes involved in viral carcinogenesis and tumor progression. Cancer Research, 6:2129-2137, 2001 (584 citations)

(6) C. Tanikawa, K. Matsuda, S. Fukuda, Y. Nakamura, and H. Arakawa: p53RDL1 regulates p53-dependent apoptosis. Nature Cell Biology, 5:216-223, 2003 (149 citations)

(7) T. Kimura, S. Takeda, Y. Sagiya, M. Gotoh, Y. Nakamura and H. Arakawa: Impaired function of p53R2 in Rrm2b-null mice causes severe renal failure through attenuation of dNTP pools. Nature Genetics, 34:440-445, 2003 (123 citations)

(8) R. Hamamoto, Y. Furukawa, M. Morita, Y. Iimura, F. P. Silva, M. Li, R. Yagyu and Y. Nakamura:  SMYD3 encodes a novel histone methyltransferase involved in the proliferation of cancer cells. Nature Cell Biology, 6:731-740, 2004 (490 citations)

(9) C. Tanikawa, M. Espinosa, A. Suzuki, K. Masuda, K. Yamamoto, E. Tsuchiya, K. Ueda, Y. Daigo, Y. Nakamura, and K. Matsuda: Regulation of histone modification and chromatin structure by the p53-PADI4 pathway.  Nature Communications, DOI 10.1038, 2012 (35 citations)

(10) H.-S. Cho, T. Shimazu, G. Toyokawa, Y. Daigo, Y. Maehara, S. Hayami, A. Ito, K. Masuda, N. Ikawa, H. I. Field, E. Tsuchiya, S. Ohnuma, B. A.J. Ponder, M. Yoshida, Y. Nakamura, and R. Hamamoto: Enhanced HSP70 lysine 561 methylation promotes proliferation of cancer cells through activation of aurora kinase B. Nature Communications, 3:DOI: 10.1038/ncomms2074, 2012 (40 citations)

(11) K. Sone, L. Piao, M. Nakakido, K. Ueda, T. Jenuwein, Y. Nakamura and R. Hamamoto Critical role of lysine 134 methylation on histone H2AX for g-H2AX production and DNA repair. Nature Communications, 5:DOI: 10.1038/ncomms6691, 2014 (8 citations)

(12) R. Hamamoto, V. Saloura and Y. Nakamura: Critical roles of non-histone protein lysine methylation in human tumorigenesis. (review article) Nature Reviews Cancer, 15:110-124, 2015

(13) R. Hamamoto, and Yusuke Nakamura: Dysregulation of protein methyltransferases in human cancer: an emerging target class for anticancer therapy. Cancer Science, DOI: 10.1111/cas.12884, 2016

(14) L. Piao, M. Nakakido, T. Suzuki, N. Dohmae, Y. Nakamura and R. Hamamoto:  Automethylation of SUV39H2, an oncogenic histone lysine methyltransferase, regulates its binding affinity to substrate proteins. Oncotarget, doi: 10.18632/oncotarget.8072, 2016

(15) V. Saloura, T. Vougiouklakis, M. Zewde, K. Kiyotani, J.-H. Park, G. Gao, T. Karrison, M. Lingen, Y. Nakamura, and R. Hamamoto:  WHSC1L1 drives cell cycle progression through transcriptional regulation of CDC6 and CDK2 in squamous cell carcinoma of the head and neck. Oncotarget, :DOI: 10.18632/oncotarget.989, 2016

(16) Y. Yoshioka, T. Suzuki, Y. Matsuo, M. Nakakido, G. Tsurita, C. Simone, T. Watanabe, N. Dohmae, Y. Nakamura and R. Hamamoto:  SMYD3-mediated lysine methylation in the PH domain is critical for activation of AKT1. Oncotarget, DOI: 10.18632/oncotarget.11898, 2016


3. Development of anti-cancer drugs (cancer peptide vaccines, antibody drugs and small molecular compounds)


Dr. Nakamura’s group has identified a number of novel molecular targets that can be applicable to development of anti-cancer drugs (molecular-targeting drug, cancer vaccine, and antibody) and reported their biological functions in human cancers. Using such information, his group has developed two monoclonal antibodies, one against FZD10 that was expressed exclusively in synovial sarcoma and the other against CDH3 that was expressed in many types of cancer. The phase I clinical trial for synovial sarcoma using 90Y-conjugated anti-FZD10 antibody is ongoing.  They with OncoTherapy Science have isolated nearly 100 peptides (HLA-A02 or HLA-A24 restricted), corresponding to a part of oncoantigens, that effectively induce cytotoxic T lymphocytes, which would specifically kill cancer cells in an HLA-A restricted and antigen-dependent manner.  They have been running translational research of these vaccines (more than 1700 patients have been enrolled).  In addition, they reported development of two novel small molecular compounds inhibiting two different oncogenic kinases, one targeting MELK (maternal embryonic leucine zipper kinase) and the other targeting TOPK (T-lymphokine-activated killer cell-originated protein kinase). MELK is a protein that was implied its involvement in the maintenance of tumor-initiating cells. TOPK plays a critical role at the final step of cytokinesis.


(1) C. Fukukawa, H. Hanaoka, S. Nagayama, T. Tsunoda, J. Toguchida, K. Endo, Y. Nakamura, and T. Katagiri: Radioimmunotherapy of human synovial sarcoma using a monoclonal antibody against FZD10. Cancer Science, 99:432-440, 2008 (43 citations)

(2) H. Yoshioka, S. Yamamoto, H. Hanaoka, Y. Iida, P. Paudya, T. Higuchi, H. Tominaga, N. Oriuchi, H. Nakagawa, Y. Shiba, K. Yoshida, R. Osawa, T. Katagiri, T. Tsunoda, Y. Nakamura, and K. Endo: In vivo therapeutic effect of CDH3/P-cadherin-targeting radioimmunotherapy. Cancer Immunology, Immunotherapy, 61:1211–1220, 2012 (9 citations)

(3) K. Kono , H. Iinuma, Y. Akutsu, H. Tanaka, N. Hayashi, Y. Uchikado, T. Noguchi, H. Fujii, K. Okinaka, R. Fukushima, H. Matsubara, M. Ohira, H. Baba, S. Natsugoe, S. Kitano, K. Yoshida, T. Tsunoda, and Y. Nakamura: Multicenter, Phase II clinical trial of Cancer Vaccination for Advanced Esophageal cancer with Three Peptides derived from Novel Cancer-Testis Antigens. Journal of Translational Medicine, 10:141, 2012 (46 citations)

(4) S. Chung, H. Suzuki, T. Miyamoto, N. Takamatsu, A. Tatsuguchi, K. Ueda, K. Kijima, Y. Nakamura and Y. Matsuo: Development of an orally-administrative MELK-targeting inhibitor that suppresses the growth of various types of human cancer. Oncotarget, 3:1629-1640, 2012 (20 citations)

(5) Y. Yoshitake, Y. Yoshitake, D. Fukuma, A. Yuno, M. Hirayama, H. Nakayama, T. Tanaka, M. Nagata, Y. Takamune, K. Kawahara, Y. Nakagawa, R. Yoshida, A. Hirosue, H. Ogi, A. Hiraki, H. Jono, A. Hamada, K. Yoshida, Y. Nishimura, Y. Nakamura, and M. Shinohara: Phase II clinical trial of multiple peptide vaccination for advanced head and neck cancer patients revealed induction of immune responses and improved OS. Clinical Cancer Research, 10:DOI: 10.1158/1078-0432.CCR-14-0202, 2014 (9 citations)

(6) H. Alachkar,  M. Mutonga, K.H. Metzeler, N. Fulton, G. Malnassy, T. Herold, K. Spiekermann, S.K. Bohlander, W. Hiddemann, Y. Matsuo, W. Stock, and Y. Nakamura: Preclinical efficacy of Maternal Embryonic Leucine-zipper Kinase (MELK) Inhibition in Acute Myeloid Leukemia. Oncotarget, 5:12371-12382, 2014 (4 citations)

(7) Y. Matsuo, J.-H. Park, T. Miyamoto, S. Yamamoto, S. Hisada, H. Alachkar, and Y Nakamura: TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis. Science Translational Medicine, 259:259ra145, 2014

(8) A. Stefka, S. Keys, J.-H. Park, Y. Matsuo, S. Chung, Y. Nakamura, A.J. Jakubowiak, and S. Rosebeck: Inhibition of maternal embryonic leucine zipper kinase (MELK) is cytotoxic to myeloma cells, overcomes drug resistance, and impairs putative myeloma stem cell replenishment of malignant plasma cells.   Blood Cancer Journal, 6:doi:10.1038/bcj.2016.71, 2016

(9) T. Kato, H. Inoue, S. Imoto, Y. Tamada, T. Miyamoto, Y. Matsuo, Y. Nakamura and J.-H. Park: Oncogenic roles of TOPK and MELK, and effective growth suppression by small molecular inhibitors in kidney cancer cells. Oncotarget, :DOI: 10.18632/oncotarget.7755, 2016

(10) H. Inoue, T. Kato, S. Olugbile, K. Tamura, S. Chung, T. Miyamoto, Y. Matsuo, R. Salgia, Y. Nakamura, and J.-H. Park: Effective growth-suppressive activity of maternal embryonic leucine-zipper kinase (MELK) inhibitor against small cell lung cancer.  Oncotarget, DOI: 10.18632/oncotarget.7297, 2016

(11) S. Chung, K. Kijima, A. Kudo, Y. Fujisawa, Y. Harada, A. Taira, N. Takamatsu, T. Miyamoto, Y. Matsuo, and Y. Nakamura: Preclinical evaluation of biomarkers associated with antitumor activity of MELK inhibitor. Oncotarget,  DOI: 10.18632/oncotarget.7685, 2016

(12) Y.E. Tarhan, T. Kato, M. Jang, Y. Haga, K. Ueda, Y. Nakamura, and J.-H. Park: Morphological changes, cadherin switching and growth suppression in pancreatic cancer by GALNT6 knockdown. Neoplasia, 18:265–272, 2016

(13) Y. Ikeda,  J.-H. Park, T. Miyamoto, N. Takamatsu, T. Kato, A. Iwasa, S. Okabe, Y. Imai, K. Fujiwara, Y. Nakamura and K. Hasegawa:  T-LAK cell-originated protein kinase (TOPK) as a prognostic factor and a potential therapeutic target in ovarian cancer. Clinical Cancer Research, :DOI: 10.1158/1078-0432.CCR-16-0207, 2016

(14) J.-H. Park, S. Chung, Y. Matsuo, and Y. Nakamura:  Development of small molecular compounds targeting cancer stem cells. (Review) MedChemComm, DOI: 10.1039/c6md00385k, 2016


4.  Development of genetic polymorphic VNTR and RFLP markers, and its application for construction of genetic linkage maps of human chromosomes and for cancer genetics

Dr. Nakamura has been making important contributions to the fields of genomic medicine and cancer research for nearly three decades. He is one of the pioneers of applying genetic variations (VNTR and RFLP markers) and genomics approach to the medical field. DNA polymorphic markers developed by his group in the laboratory of Professor Ray White at the University of Utah had made it possible to map and clone genes responsible for hereditary diseases. Using these DNA markers and genetic maps, many scientists around the world had been able to show the usefulness of the reverse genetics method. In fact, many genes responsible for hereditary diseases were mapped and cloned by the use of the DNA markers and chromosomal maps developed in the White laboratory. Such discoveries include genes responsible for neurofibromatosis type 1, familial polyposis coli, multiple endocrine neoplasia type 1, familial breast cancer, and ataxia telangiectasia etc.  In addition, these markers were applied to examine loss of heterozygosity for all of human chromosomes and contributed to establish the concept of multi-step carcinogenesis of human cancer.  Some of VNTR markers were also used in the forensic science field.


(1) Y. Nakamura, M. Leppert, P. O'Connell, Roger Wolff, T. Holm, M. Culver, C. Martin, E. Fujimoto, M. Hoff, E. Kumlin and R. White: Variable number of tandem repeat (VNTR) markers for human gene mapping. Science, 235:1616-1622, 1987 (1768 citations)

(2) C. Larsson, B. Skogseid, K. Obeg, Y. Nakamura, M. Nordenskjold: Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature, 332:85-87, 1988 (968 citations)

(3) D. Barker, E. Wright, K. Nguyen, L. Cannon, P. Fain, D. Goldger, D. T. Bishop, J. Carey, B. Bety, H. Willard, J. S. Waye, G. Greig, L. Leinward, Y. Nakamura, P. O'Connell, M. Leppert, J.-M. Lalouel, R. White and M. Skolnick: Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of chromosome 17. Science, 236:1100-1102, 1987 (681 citations)

(4) B. Vogelstein, E.R. Fearon, S.E. Kern, S.R. Hamilton, A.C. Preisinger, Y. Nakamura and R. White: Allelotype of colorectal carcinomas. Science, 244:207-211, 1989 (1361 citations)

(5) B. Vogelstein, E.R. Fearon, S.R. Hamilton, S. Kern, A.C. Presinger, M. Leppert, Y. Nakamura, R. White, L. Smets and J.L. Bos: Genetic alterations during colorectal tumor development.  New Eng. J. Med., 319:525-532, 1988 (6028 citations)

(6) R.A. Gatti, I. Berkel, E. Border, G. Braedt, P. Charmley, P. Concannon, F. Ersoy, T. Foroud, N.J.G. Jaspers, K. Lange, G.M. Lathrop, M. Leppert, Y. Nakamura, M. Paterson, W. Salser, O. Sanal, W. Shan, J. Silver, R.S. Sparkes, E. Susi, D. Weeks, R. White and F. Yoder: Localization of ataxia-telangiectasia gene to chromosome 11q22.3. Nature, 336:577-580, 1988 (598 citations)

(7) S. Kern, E. Fearon, K.W.F. Tersmette, J.P. Enterline, M. Leppert, Y. Nakamura, R. White, B. Vogelstein and S. Hamilton: Allelic loss in colorectal carcinoma. JAMA, 261:3099-3103, 1989 (397 citations)

(8) M. Leppert, E. Anderson, T. Quattlebaum, D. Stauffer, P. O'Connell, Y. Nakamura, J-M. Lalouel and R. White: Mapping of the seizure gene: Benign familial neonatal convulsions linked to genetic makers on chromosome 20.Nature, 337:647-648, 1989 (372 citations)

(9) K. Kasai, Y. Nakamura and R. White: Amplification of a VNTR locus (pMCT118) by the polymerase chain reaction (PCR) and its application to forensic science. J. Forensic Sci., 35:1196-1200, 1990 (401 citations)

(10) T. Sato, A. Tanigami, K. Yamakawa, F. Akiyama, F. Kasumi, G. Sakamoto and Y. Nakamura: Allelotype of breast cancer: Cumulative allele losses promote tumor progression in primary breast cancer. Cancer Research, 50:7184-7189, 1990 (499 citations)


5. Cloning and characterization of the APC gene responsible for familial polyposis coli as well as other genetic diseases

During the period worked at University of Utah and in Cancer Institute (Tokyo), Dr. Nakamura collaborated with a group led by Prof. Bert Vogelstein at Johns Hopkins Medical Center in Baltimore, MD, and was able to identify an APC gene that is responsible for familial adenomatous polyposis coli (FAP).  His group characterized the germline mutations in FAP patients.  This discovery made it a possible to make a pre-symptomatic diagnosis of FAP.  His group in Tokyo also analyzed the APC gene in sporadic colorectal adenomas and carcinomas, and identified the mutation cluster region of the APC gene in sporadic tumors.  In addition, his group isolated or contributed to isolation of genes responsible some genetic diseases such as Marfan syndrome, Fukuyama type congenital muscular dystrophy, posterior longitudinal ligament of the spine, gelatinous drop-like corneal dystrophy.


(1) K.W. Kinzler, M.C. Nilbert, L. Su, B. Vogelstein, T.M. Bryan, D.B. Levy, K.J. Smith, A.C. Preisinger, P. Hedge, D. McKechnie, R. Finniear, A. Markham, J. Groffen, M.S. Boguski, S.F. Alschul, A. Horii, H. Ando, Y. Miyoshi, Y. Miki, I. Nishisho, Y. Nakamura: Identification of FAP locus genes from chromosome 5q21. Science, 253:661-665, 1991 (2107 citations)

(2) I. Nishisho, Y. Nakamura, Y. Miyoshi, Y. Miki, H. Ando, A. Horii, K. Koyama, J. Utsunomiya, S. Baba, P. Hedge, A. Markham, A.J. Krush, G. Petersen, S.R. Hamilton, M.C. Nilbert, D.B. Levy, T.M. Bryan, A.C. Preisinger, K.J. Smith, L. Su, K.W. Kinzler, and B. Vogelstein: Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science, 253:665-669, 1991 (1622 citations)

(3) Y. Miyoshi, H. Nagase, H. Ando, A. Horii, S. Ichii, S. Nakatsuru, T. Aoki, Y. Miki, T. Mori and Y. Nakamura: Somatic mutation of the APC gene in colorectal tumors: mutation cluster region in the APC gene. Human Molecular Genetics, 1:229-233, 1992 (864 citations)

(4) Y. Miyoshi, H. Ando, H. Nagase, I. Nishisho, A. Horii, Y. Miki, T. Mori, J. Utsunomiya, S. Baba, G. Petersen, S.R. Hamilton, K.W. Kinzler, B. Vogelstein, Y. Nakamura: Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients. Proc. Natl. Acad. Sci. USA, 89:4452-4456, 1992 (480 citations)

(5) Y. Miki, I. Nishisho, A. Horii, Y. Miyoshi, J. Utsunomiya, K. Kinzler, B. Vogelstein. Y. Nakamura: Disruption of the APC gene by retrotransposal insertion of L1 sequence in a colon cancer. Cancer Research, 52:643-645, 1992 (376 citations)

(6) H. Shibata, K. Toyama, H. Shioya, M. Ito, M. Hirota, S. Hasegawa, H. Matsumoto, H. Takano, T. Akiyama, K. Toyoshima, R. Kanamaru, Y. Kanegae, I. Saito, Y. Nakamura, K. Shiba, and T. Noda: Rapid colorectal  adenoma formation initiated by conditional targeting of the APC gene. Science, 278:120-123, 1997 (394 citations)

 (7) K. Kobayashi, Y. Nakahori, M. Miyake, Y. Nomura, M. Yoshioka, K. Saito, M. Osawa, J. Goto, Y. Nakagome, I. Kanazawa, Y. Nakamura, K. Tokunaga, and T. Toda: An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy (FCMD). Nature, 394:388-392, 1998 (663 citations)

(8) A. Okawa, I. Nakamura, S. Goto, H. Moriya, Y. Nakamura, and S. Ikegawa: Mutation in Npps in a mouse model of ossification of the posterior longitudinal ligament of the spine. Nature Genetics, 19:271-273, 1998 (311 citations)

(9) M. Tsujikawa, H. Kurahashi, T. Tanaka, K. Nishida, Y. Shimomura, Y. Tano, and Y. Nakamura: Identification of the gene responsible for gelatinous drop-like corneal dystrophy. Nature Genetics, 21:420-423, 1999 (125 citations)

(10) T. Mizuguchi, G. Collod-Beroud, T. Akiyama, M. Abifadel, N. Harada, T. Morisaki, D. Allard, M. Varret, M. Claustres, H. Morisaki, M. Ihara, A. Kinoshita, K. Yoshiura, C. Junien, T. Kajii, G. Jondeau, T. Ohta, T. Kishino, Y. Furukawa, Y. Nakamura, N. Niikawa, C. Boileau, and N. Matsumoto: Heterozygous TGFBR2 mutations in Marfan syndrome. Nature Genetics, 36:855-860, 2004 (486 citations)


6. Contribution to the International HapMap project as well as leading Biobank Japan project and GWAS and pharmacogenomics studies

In 2000-2011, he led the Japanese SNP project in the Japanese Millennium genome project, the Japanese group of the International HapMap project, as well as the Biobank Japan and pharmacogenomics project.  Under his leadership, the Japanese group constructed the JSNP database, and contributed to the success of the HapMap project by generation of nearly one fourth of the Phase I data in the project (that was the largest contribution among the participating centers in the world).  The Biobank Japan project collected DNAs of 300,000 cases covering 47 diseases.  The RIKEN group began the genome-wide association approach to identify susceptibility genes for common diseases in 2001.  The RIKEN group led by him reported nearly 100 GWAS papers including 54 papers in Nature Genetics, including genes susceptible to common diseases such as genes associated with myocardial infarction, rheumatoid arthritis, diabetic nephropathy, IgA nephropathy, osteoarthritis, brain Infarction, Kawasaki disease, asthma, atopic dermatitis, endometriosis, keloid disease, Crohn disease and various types of cancer.


(1) The International HapMap Consortium: A haplotype map of the human genome. Nature, 437:1299-1320, 2005 (4209 citations)

(2) The International HapMap Consortium: The International HapMap Project. Nature, 426:789-796, 2003 (3528 citations)

(3) The International HapMap Consortium: A second generation human haplotype map of over 3.1 million SNPs. Nature, 449:851-861, 2007 (3446 citations)

(4) K. Ozaki, Y. Ohnishi, A. Iida, A. Sekine, R. Yamada, T. Tsunoda, H. Sato, H. Sato, M. Hori, Y. Nakamura, and T. Tanaka: Functional SNPs in the lymphotoxin-α gene that are associated with susceptibility to myocardial infarction. Nature Genetics, 32:650-654, 2002 (785 citations)

(5) A. Suzuki, R. Yamada, X. Chang, S.Tokuhiro, T. Sawada, M. Suzuki, M. Nagasaki, M. Nakayama-Hamada, R.Kawaida, M. Ono, M. Ohtsuki, H. Furukawa, S. Yoshino, M. Yukioka, S. Touma, T. Matsubara, S. Wakitani, R. Teshima, A. Sekine, A.Iida, A. Takahashi, T. Tsunoda, Y. Nakamura, and K. Yamamoto: Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nature Genetics, 34:395-402, 2003 (931 citations)

(6) The International Warfarin Pharmacogenetics Consortium: Estimation of the warfarin dose with clinical and pharmacogenetic data. New Eng. J. Med., 360:753-764, 2009 (980 citations)

(7) S. Uno, H. Zembutsu, A. Hirasawa, A. Takahashi, M. Kubo, T. Akahane, D. Aoki, N. Kamatani, K. Hirata, and Y. Nakamura: A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese.  Nature Genetics, 42:707-710, 2010 (117 citations)

(8) D. Miki, M. Kubo, A. Takahashi, K.-A. Yoon, J. Kim, G.-K. Lee, J.I. Zo, J.S. Lee, N. Hosono, T. Morizono, T. Tsunoda, N. Kamatani, K. Chayama, T. Takahashi, J. Inazawa, Y. Nakamura, and Y. Daigo: Variation in TP63 is associated with lung adenocarcinoma susceptibility in Japanese and Korean population.  Nature Genetics, 42:893-896, 2010 (97 citations)

(9) P.-C. Cha, A. Takahashi, N. Hosono, S.-K. Low, N. Kamatani, M. Kubo, and Y. Nakamura: A genome-wide association study identifies three loci associated with susceptibility to uterine fibroids. Nature Genetics, 43:447-450, 2011 (48 citations)

(10) N.J. Choudhury, A. Campanile, T. Antic, K.L. Yap, C. Fitzpatrick, J.L. Wade III, T. Karrison, W.M. Stadler, Y. Nakamura, P.H. O’Donnell:  Afatinib activity in platinum-refractory metastatic urothelial carcinoma in patients with ERBB alterations. Journal of Clinical Oncology, doi: 10.1111/cas.12862, 2016

(11) H. Zembutsu, S. Nakamura, S. Akashi-Tanaka, T. Kuwayama, C. Watanabe, T. Takamaru, H. Takei, T. Ishikawa, K Miyahara, H. Matsumoto, Y. Hasegawa, G.Kutomi, H. Shima, F. Satomi, M. Okazaki, H. Zaha, M. Onomura, A. Matsukata, Y. Sagara, S. Baba, A. Yamada, K. Shimada, D. Shimizu, K. Tsugawa, A. Shimo, T.E. Yu, M. Hartman, C.C. Wan, S.C. Lee, and Y. Nakamura: Significant effect of polymorphisms in CYP2D6 on response to tamoxifen therapy for breast cancer; a prospective multicenter study. Clinical Cancer Research, in press, 2016