教員プロフィール

山田 俊幸

山田 俊幸 教授

山田 俊幸

遺伝子から病気を理解する

生命の設計図である遺伝子が壊れたり、その発現が異常になったりすると病気の原因になります。私はこれまで、ヒトやモデル動物のがん、免疫異常、臓器の異常などについて原因遺伝子の解明や、発症機序の解明をおこなってきました。これらの情報を次の段階、すなわち病気を治すということにつなげたいと思っています。この緑豊かなキャンパスで薬剤師という資格を取得するために勉強できる学生諸君はとても幸せだと思います。どうか一日一日、一瞬一瞬を大切にして充実した学生生活を送って欲しいと思います。

略歴

北海道大学大学院理学研究科修了、理学博士。
英国 Royal Free Hospital 医学部研究員、財団法人佐々木研究所主任研究員、弘前大学医学部准教授を経て現職。

総説

  • Yamada T、Tsuchida S. The Hirosaki small-eye rat: A novel recessive model animal of lens and retinal degeneration with loss of A3/A1-crystallin. Precision Medicine, 2: e1140. doi: 10.14800/pm.1140, 2016.
  • Yamada T、Tsuchida S. Ly49 and C-type lectin receptors on dendritic cells regulate T-cell differentiation as co-stimulatory molecules. Receptor Clin Invest., 1:101-111, 2014.
  • Oikawa T, Yamada T. Morecular biology of the Ets family of transcription factors. Gene, 303:11-34, 2003.
  • Oikawa T, Yamada T, Kihara-Negishi F, Yamamoto H, Kondoh N, Hitomi Y, Hashimoto Y. The role of Ets family transcription factor PU.1 in hematopoietic cell differentiation, proliferation and apoptosis. Cell Death and Differ., 6:599-608, 1999.
  • 及川恒之、山田俊幸. 顆粒球分化の転写制御. Molecular Medicine. 2001; 38:778-783, 2001.
  • 山田俊幸、及川恒之. ヒトpre-B急性リンパ性白血病における1;19染色体転座の分子機構. オンコロジア, 25:36-41,1992.

学術論文

  • Yamada T, Nanashima N, Shimizu T, Nakazawa Y, Nakazawa M, Tsuchida S. Establishment of a recessive mutant small-eye rat with lens involution and retinal detachment associated with partial deletion and rearrangement of the Cryba1 gene. Biochem J., 471:293-305, 2015.
  • Nanashima N, Yamada T, Shimizu T, Tsuchida S. Deletion of phospholipase A2 group IVc induces apoptosis in rat mammary tumor cells by the nuclear factor-kB/lipocalin 2 pathway. Biochem J., 469:315-324, 2015.
  • Yamada T, Nanashima N, Akita M, Shimizu T, Miura T, Yamana D, Sawano T, Sakurai T, Tsuchida S. Lectin-like receptor Ly49s3 on dendritic cells contributes to the differentiation of regulatory T cells in the rat thymus. J Immunol., 191:3799-3809, 2013.
  • Wu Y, Sato F, Yamada T, Bhawal UK, Kawamoto T, Fujimoto K, Noshiro M, Seino H, Morohashi S, Hakamada K, Abiko Y, Kato Y, Kijima H. The bHLH transcription factor DEC1 plays important roles in epithelial-mesenchymal transition of pancreatic cancer. Int J Oncol., 41:1337-1346, 2012.
  • Miura T, Kimura N, Yamada T, Shimizu T, Nanashima N, Yamana D, Hakamada K, Tsuchida S. Sustained repression and translocation of Ntcp and expression of Mrp4 for cholestasis after rat 90% partial hepatectomy. J Hepatol., 55:407-414, 2011.
  • Hashiguchi K, Tsuchiya H, Tomita A, Ueda C, Akechi Y, Sakabe T, Kurimasa A, Nozaki B, Yamada T, Tsuchida S, Shiota G. Involvement of ETS1 in thioredoxin-binding protein 2 transcription induced by a synthetic retinoid CD437 in human osteosarcoma cells. Biochem Biophys Res Commun., 391:621-626, 2010.
  • Fan Y, Yamada T, Shimizu T, Nanashima N, Akita M, Suto K, Tsuchida S. Ferritin expression in rat hepatocytes and Kupffer cells after lead nitrate treatment. Toxicol Pathol., 37:209-217, 2009.
  • Yamada T, Shimizu T, Sakurai T, Nanashima N, Kihara-Negishi F, Suzuki M, Fan Y, Akita M, Oikawa T, Tsuchida S. Physical and functional interactions between hematopoietic cell-specific ETS transcription factors and homeodomain proteins. Leuk Res., 33:483-489, 2009.
  • Nanashima N, Akita M, Yamada T, Shimizu T, Nakano H, Fan Y, Tsuchida S. The hairless phenotype of the Hirosaki Hairless Rat is due to the deletion of an 80-kb genomic DNA containing five basic keratin genes. J Biol Chem., 283:16868-16875, 2008.
  • Yamada T, Shimizu T, Suzuki M, Kihara-Negishi F, Nanashima N, Sakurai T, Fan Y, Akita M, Oikawa T, Tsuchida S. Interaction between the homeodomain protein HOXC13 and ETS family transcription factor PU.1 and its implication in the differentiation of murine erythroleukemia cells. Exp Cell Res., 314:847-858, 2008.
  • Sakurai T, Kondoh N, Arai M, Hamada J, Yamada T, Kihara-Negishi F, Izawa T, Ohno H, Yamamoto M, Oikawa T. Functional roles of Fli-1, a member of the Ets family of transcription factors, in human breast malignancy. Cancer Sci., 98:1775-1784, 2007.
  • Igarashi M, Yoshida M, Watanabe M, Yamada T, Sakurai T, Endo Y, Miyajima N, Maekawa A, Oikawa T, Sugano S, Nakae D. Involvement of mutation-based inhibition of -catenin phosphorylation at ser33 in the malignant progression of lung (pre)neoplastic lesions induced by N-nitrosobis(2-hydroxypropyl)amine in male Fischer 344 rats. Lung, 185:271-278, 2007.
  • Nakazawa Y, Suzuki M, Manabe N, Yamada T, Kihara-Negishi F, Sakurai T, Tenen DG, Iwama A, Mochizuki M, Oikawa T. Cooperative interaction between ETS1 and GFI1 transcription factors in the repression of Bax gene expression. Oncogene, 26:3541-3550, 2007.
  • Suzuki M, Yamada T, Kihara-Negishi F, Sakurai T, Hara E, Tenen DG, Hozumi N, Oikawa T. Site-specific methylation by a complex of PU.1 and Dnmt3a/b. Oncogene, 25:2477-2488, 2006.
  • Nanashima N, Asano J, Hayakari M, Nakamura T, Nakano H, Yamada T, Shimizu T, Akita M, Fan Y, Tsuchida S. Nuclear localization of STAT5A modified with O-linked N- acetylglucosamine and early involution in the mammary gland of Hirosaki Hairless Rat. J Biol Chem., 280:43010-43016, 2005.
  • Teramoto S, Kihara-Negishi F, Sakurai T, Yamada T, Hashimoto-Tamaoki T, Tamura S, Kohno S, Oikawa T. Classification of neural differentiation-associated genes in P19 embryonal carcinoma cells by their expression patterns induced after cell aggregation and/or retinoic acid treatment. Oncol. Rep., 14:1231-1238, 2005.
  • Kihara-Negishi F, Suzuki M, Yamada T, Sakurai T, Oikawa T. Impaired repressor activity and biological functions of PU.1 in MEL cells induced by mutations in the acetylation motifs within the ETS domain. Biochem Biophys Res Commun., 335:477-484, 2005.
  • Yamada T, Suzuki M, Satoh H, Kihara-Negishi F, Nakano H, Oikawa T. Effects of PU.1-induced mouse calcium-calmodulin-dependent kinase I-like kinase (CKLiK) on apoptosis of murine erythroleukemia cells. Exp Cell Res., 294:39-50, 2004.
  • Suzuki M, Yamada T, Kihara-Negishi F, Oikawa T. Direct association between PU.1 and MeCP2 that recruits mSin3A-HDAC complex for PU.1-mediated transcriptional repression. Oncogene, 22:8688-8698, 2003.
  • Manabe N, Yamamoto H, Yamada T, Kihara-Negishi F, Hashimoto Y, Mochizuki M, Oikawa T. Prevention of PU.1-induced growth inhibition and apoptosis but not differentiation block in murine erythroleukemia cells by overexpression of CBP. Int J Oncol., 22:1345-1350, 2003.
  • Sakurai T. Yamada T, Kihara-Negishi F, Teramoto S, Sato Y. Izawa T, Oikawa T. Effects of overexpression of the Ets family transcription factor TEL on cell growth and differentiation of K562 cells. Int J Oncol., 22:1327-1333, 2003.
  • Yamamoto H, Kihara-Negishi F, Yamada T, Suzuki M, Nakano T, Oikawa T. Interaction between the hematopoietic Ets transcription factor Spi-B and the coactivator CBP associated with negative cross-talk with c-Myb. Cell Growth Differ., 13:69-75, 2002.
  • Kihara-Negishi F, Yamamoto H, Suzuki M, Yamada T, Sakurai T, Tamura T, Oikawa T. In vivo complex formation of PU.1 with HDAC1 associated with PU.1-mediated transcriptional repression. Oncogene, 20:6039-6047, 2001.
  • Oikawa T, Yamada T, Kondoh N, Kihara-Negishi F, Hitomi Y, Suzuki M, Teramoto S. Extinction of expression of the genes encoding hematopoietic cell-restricted transcription factors in T lymphoma×fibroblast cell hybrids. Immunology, 104:164-167, 2001.
  • Yamada T, Abe M, Higashi T, Yamamoto H, Kihara-Negishi F, Sakurai T, Shirai T, Oikawa T. Lineage switch induced by overexpression of Ets family transcription factor PU.1 in murine erythroleukemia cells. Blood, 97:2300-2307, 2001.
  • Yamamoto H, Kihara-Negishi F, Yamada T, Hashimoto Y, Oikawa T. Physical and functional interactions between the transcription factor PU.1 and the coactivator CBP. Oncogene, 18:1495-1501, 1999.
  • Yamada T, Kihara-Negishi F, Yamamoto H, Yamamoto M, Hashimoto Y, Oikawa T. Reduction of DNA binding activity of the GATA-1 transcription factor in the apoptotic process induced by overexpression of PU.1 in murine erythroleukemia cells. Exp Cell Res., 245:186-194, 1998.
  • Kondoh N. Yamada T, Kihara-Negishi F, Yamamoto M, Oikawa T. Enhanced expression of the urokinase-type plasminogen activator gene and reduced colony formation in soft agar by ectopic expression of PU.1 in HT1080 human fibrosarcoma cells. Br J Cancer, 76:718-723, 1998.
  • Kihara-Negishi F, Yamada T, Kubota Y, Kondoh N, Yamamoto H, Abe M, Shirai T, Hashimoto Y, Oikawa T. Down-regulation of c-Myc and Bcl-2 gene expression in PU.1-induced apoptosis in murine erythroleukemia cells. Int J Cancer, 76:523-530, 1998.
  • Yamada T, Kondoh N, Matsumoto M, Yoshida M, Maekawa A, Oikawa T. Overexpression of PU.1 induces growth and differentiation inhibition and apoptotic cell death in murine erythroleukemia cells. Blood, 89:1383-1393, 1997.
  • Musashi M, Abe S, Yamada T, Tanaka J, Gotohda Y, Maeda S, Sato Y, Morioka M, Sakurada K, Minagawa T, Asaka M, Miyazaki T. Spontaneous remission in a patient with chronic myelogenous leukemia. N Engl J Med., 336:337-339, 1997.
  • Oikawa T, Yamada T, Kubota Y, Kondoh N, Hitomi Y, Uchiumi F, Yamamoto T. Suppression of lck protooncogene expression in murine somatic cell hybrids between T lymphoma cells and fibroblasts. Cytogenet Cell Genet., 72:12-19, 1996.
  • Yamada T, Hitomi Y, Satake M, Oikawa T. Differential expression of the TCR/CD3 genes and their lymphoid-specific transcription factor genes in murine T-cell x fibroblast and T-cell x B-cell hybrids. Eur J Immunol., 25:2710-2713, 1995.
  • Hitomi Y, Yamada T, Oikawa T. Extinction of expression of the PU.1/Spi-1 putative oncogene encoding a B cell- and macrophage-specific transcription factor in somatic cell hybrids. Cancer Res., 53:5759-5765, 1993.
  • Yamada T, Hitomi Y, Shimizu K, Ohki M, Oikawa T. Extinction of T cell receptor alpha-chain gene expression accompanied by loss of the lymphoid enhancer-binding factor 1 (LEF-1) in murine somatic cell hybrids. Mol Cell Biol., 13:1943-1950, 1993.
  • Secker-Walker LM, Morgan GJ, Min T, Swansbury GJ, Craig J, Yamada T, Desalvo L, Medina JW, Chowdhury V, Donahue RP, Polliack A, Catovsky D. Inversion of chromosome 16 with the Philadelphia chromosome in acute myelomonocytic leukemia with eosinophilia: report of two cases. Cancer Genet Cytogenet., 58:29-34, 1992.
  • Yamada T, Craig JM, Hawkins JM, Janossy G, Secker-Walker LM. Molecular investigation of 19p13 in standard and variant translocations: the E12 probe recognizes the 19p13 breakpoint in cases with t(1;19) and acute leukemia other than pre-B immunophenotype. Leukemia, 5:36-40, 1991.
  • Craig JM, Hawkins JM, Yamada T, Ganeshaguru K, Metha AB, Secker-Walker LM. First intron and M-bcr breakpoints are restricted to the lymphoid lineage in Philadelphia positive acute lymphoblastic leukaemia. Leukemia, 4:678-681, 1990.
  • Garipidou G, Yamada T, Prentice HG, Secker-Walker LM. Trisomy 8 in acute lymphoblastic leukaemia (ALL): a case report and update of the literature. Leukemia, 4:717-719, 1990.
  • Yamada T, Shippey CA, Martineau M, Secker-Walker LM. Demonstration of acquired hemizygosity and clonality in acute lymphoblastic leukaemia with chromosome 7 abnormalities using hypervariable DNA probes. Genes Chromosomes & Cancer, 2:88-93, 1990.
  • Yamada T, Craig JM, Secker-Walker LM. Isochromosome 7q is restricted to the lymphoid lineage in T cell acute lymphoblastic leukaemia. Br J Haematol., 75:137-138, 1990.
  • Yamada T, Secker-Walker LM. Possible evidence for acquired genetic activity at both chromosomal breakpoints of the Philadelphia translocation in chronic myeloid leukemia. Leukemia, 4:341-344, 1990.
  • Yamada T, Oikawa T, Kuzumaki N, Takagi N, Sasaki M. Absence of the hybrid bcr-abl mRNA in Ph1-positive B lymphoblastoid cell lines established from a patient with chronic myelogenous leukemia. Int J Cancer, 40:778-783, 1987.
  • Oikawa T, Kuzumaki N, Yamada T, Chiba I, Yamagiwa S. Suppression of transformed phenotype in intraspecific somatic cell hybrid clones between the c-myc activating mouse plasmacytoma line and normal cells. Int J Cancer, 39:604-610, 1987.
  • Yamada T, Sasaki M. Differentiation by a tumor promoter of lymphoblastoid cell lines with and without Ph1 chromosome from a chronic myelogenous leukemia patient. Jpn J Cancer Res (Gann)., 78:499-504, 1987.
  • Yamada T, Sasaki M, Sakurama T. Trisomy 11 in a patient with Ph-negative chronic myelogenous leukemia. Cancer Genet Cytogenet., 21:343-345, 1986.
  • Yamada T, Sasaki M, Yoshida MC, Aya T, Koizumi S, Osato T. Establishment and characterization of Ph1-positive and Ph1-negative lymphoblastoid cell lines from a patient with chronic myelogenous leukemia. Jpn J Cancer Res (Gann)., 76:365-373, 1985.
  • Kuzumaki N, Oikawa T, Yamada T. Independent expression of common and private specific cell surface antigens in somatic cell hybrids between Rous sarcoma virus-transformed and normal cells. J Natl Cancer Inst., 72:387-393, 1984.
  • Oikawa T, Kuzumaki N, Yamada T. Specific chromosome translocation in pristane-induced plasmacytomas of NZB mice. J Natl Cancer Inst., 72:347-353, 1984.
  • Yamada T, Sasaki M, Nishihira J, Sakurama S, Nakagawa S. Clonal origin of Ph1-positive cells in a case of 46,XX/47,XXX/48,XXXX mosaicism associated with chronic myelocytic leukemia. Proc Jpn Acad., 59:163-167, 1983.

海外および国際学会発表

  • Yamada T, Nanashima N, Shimizu T, Tsuchida S. Differentiation inhibition of regulatory T cells in Hirosaki hairless rat due to deletion of the Ly49 family genes expressed in thymic T cells and dendritic cells. 13th Meeting of the Hirosaki International Forum of Medical Science, Hirosaki, Japan, 2011.
  • Yamada T, Shimizu T, Asano J, Akita M, Nanashima N, Fan Y, Oikawa T, Tsuchida S. Involvement of homeobox protein HOXC13 in differentiation of mouse erythroleukemia cells. 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress, Kyoto, Japan, 2006.
  • Yamada T, Suzuki M, Satoh H, Kihara-Negishi F, Nakano H, Sakurai T, Oikawa T, Tsuchida S. Effects of PU.1-induced mouse calcium-caimodulin-dependent kinase I-like kinase (CKLiK) on apoptosis of murine erythroleukemia cells. 9th Meeting of the Hirosaki International Forum of Medical Science, Hirosaki, Japan, 2005.
  • Yamada T, Nakazawa Y, Manabe N, Mochizuki M, Oikawa T. Cooparative and antagonistic interactions between ETS and Gfi-1 transcription factor families. JBS International Symposium in 2005, New Frontier of Transcription Research, Kusatsu, Japan, 2005.
  • Yamada T, Yamamoto H , Kihara-Negishi F, Oikawa T. GATA-1 and CBP are involved in apoptosis of MEL cells induced by overexpression of PU.1. The 2nd International Meeting of GATA protein, Tsukuba, Japan, 2000.
  • Yamada T, Oikawa T. Induction of apoptosis by overexpression of the PU.1 gene in murine erythroleukemia cells. The 18th Symposium of the International Association for Comparative Research on Leukemia and Related Diseases, Kyoto, Japan, 1995.
  • Yamada T, Oikawa T. Extinction of T cell receptor (TCR) gene expression accompanied by loss of the lymphoid enhancer-binding factor 1 (LEF-1) in murine cell hybrids. The 8th International Conference of the International Society of Differentiation, Hiroshima, Japan, 1994.
  • Yamada T, Craig JM, Hawkins JM, Janossy G, Secker-Walker LM. Molecular demonstration of heterogeneity of the 19p13 breakpoint in t(1;19) and variant translocations in pre-B acute lymphoblastic leukemia and other hematological malignancies. The 33rd Congress of International Society of Hematology and The 32nd Annual Meeting of American Society of Hematology, Boston, USA, 1990.

研究費の受入状況

最近10年間の受入状況

  • (文部科学省科研費)
    平成24〜26年度、基盤研究C一般、
    「免疫抑制遺伝子Ly49を欠損した新しい免疫疾患モデルラットの確立」、400万円、代表.
  • 平成27〜29年度、基盤研究C一般、
    「新規動物モデルを用いたヘルパーT細胞分化に対する細胞内ビタミンAの作用機序の解明」、380万円、代表.
  • (他の省庁からの助成金)
    平成19〜21年度、内閣府・食品健康影響評価技術研究、
    「遺伝子多型ラットを用いたペルオキシソーム増殖剤のヒト発がんリスク評価法の開発」、360万円、分担.
  • (その他の助成金)
    平成19年度、第24回唐牛記念医学研究基金研究助成金、
    「白血病発症におけるETSファミリー転写因子とホメオドメインタンパク質の相互作用の役割」、350万円、代表.

著書

  • Tsuchida S, Yamada T. Glutathione transferases. Reference Module in Biomedical Research. London: Elsevier, pp1-13, 2014.
  • Oikawa T, Yamada T, Kihara-Negishi F, Sakurai T. Ets family of transcription factors in normal hematopoiesis and in leukemogenesis. In Sinnett D, editor. Molecular Genetics of Cancer. Trivandrum India: Research Signpost, pp119-148, 2005.
  • 山田俊幸. メンデルの法則とは何か? 大野秀樹、及川恒之、石井直方編. Q&A 運動と遺伝. 東京: 大修館書店, pp6-7, 2002.
  • 山田俊幸. 性はどのように決定されるのか? 大野秀樹、及川恒之、石井直方編. Q&A 運動と遺伝. 東京: 大修館書店, pp8-9, 2002.
  • 山田俊幸. 遺伝情報は細胞のどこに収納されるのか? 大野秀樹、及川恒之、石井直方編. Q&A 運動と遺伝. 東京: 大修館書店, pp12-13, 2002.

シンポジウム等

  • 山田俊幸. 眼球の白濁、水晶体の退縮、網膜の剥離を示す遺伝性小眼球ラット(Hirosaki Small Eye Rat; HiSER)におけるCryba1遺伝子の欠失. 第55回日本白内障学会総会、第42回水晶体研究会 合同学会、シンポジウム、 盛岡、2016.
  • Yamada T, Shimizu T, Nanashima N, Akita M, Fan Y, Oikawa T, Tsuchida S. Interactions between ETS family transcription factors and homeoproteins involved in hematopoiesis and leukemogenesis. 第67回日本癌学会総会、ワークショップ、名古屋、2008.
  • 山田俊幸、及川恒之. PU.1により発現誘導されるカルモデュリン依存性キナーゼによるMEL細胞の増殖抑制とアポトーシス. 第65回日本血液学会総会、ワークショップ、大阪、2003.
  • 山田俊幸、白井俊一、及川恒之. EtsファミリーPU.1によるマウス赤白血病(MEL)細胞の分化のシフト.第59回日本癌学会総会、ミニシンポジウム、横浜、2000.