Tetsuya Nosaka, MD, PhD


経歴

 

 

1985年三重大学医学部を卒業後、すぐに京都大学大学院に入学、ウイルス研究所 畑中正一教授の下でレトロウイルス学と分子生物学を学ぶ。この間、一年間、国内留学により三重大学第二内科(白川茂教授)で臨床血液学も学ぶ。1989年、京都大学医学博士、同年4月、畑中研の助手(助教)となる。19942月、京大休職で米国St Jude Childrens Research Hospital留学(James N. Ihle教授)。1995年、Seattleでのアメリカ血液学会で、当時DNAXにおられた北村俊雄博士と知り合いになり、その後、北村博士が東大でラボを主宰されるのを機に、スタッフに採用され、帰国。199612月、東京大学医科学研究所造血因子探索寄付研究部門助手(助教)、199911月より同寄付研究部門助教授(准教授)、200612月より三重大学大学院医学系研究科教授。専門は白血病の分子生物学、ベクター開発、ウイルス学。「ど基礎」から臨床まで興味の範囲が広いのは、畑中研で育ったことと無縁ではないと思われる。細胞内情報伝達機構の解析と、成功を信じて正攻法で臨む研究スタイルをIhle研で学び、レトロウイルスを使った遺伝子発現クローニングと研究展開のエッセンスを北村研で学んだ。上記の他にも多くの師匠に恵まれ、故北堅吉先生(元三重大学准教授)からは鋭い観察・洞察力の大切さ、本庶佑教授(2018年ノーベル賞)からはずばり本質に迫る単純明快性、Peter C. Doherty教授(1996年ノーベル賞)からは既成概念に囚われない柔軟な思考を学んだ。幼き頃、天体望遠鏡を通して生で見た土星のリングの神秘的美しさに思わず息を呑んだような経験は誰しもあると思うが、そのような感動を忘れず、「美しい」研究を目指している。

 

研究業績

Original Articles

 

1. Nosaka T, Ohno H, Doi S, Fukuhara S, Miwa H, Kita K, Shirakawa S, Honjo T, Hatanaka M. Phenotypic conversion of T-lymphoblastic lymphoma to acute biphenotypic leukemia composed of lymphoblasts and myeloblasts: Molecular genetic evidence of the same clonal origin. J Clin Invest 81: 1824-1828, 1988.

 

2. Siomi H, Shida H, Nam SH, Nosaka T, Maki M, Hatanaka M. Sequence requirements for nucleolar localization of human T cell leukemia virus type I pX protein, which regulates viral RNA processing. Cell 55: 197-209, 1988.

 

3. Siomi H, Nosaka T, Saida T, Miwa H, Hinuma Y, Shirakawa S, Miyamoto N, Kondo T, Araki K, Ichimaru M, Miura AB, Hatanaka M. Two major subgroups of HTLV-I in Japan. Virus Genes 1: 377-383, 1988.

 

4. Ohno T, Kanoh T, Arita Y, Fujii H, Kuribayashi K, Matsuda T, Horiguchi Y, Taniwaki M, Nosaka T, Hatanaka M, Uchino H. Fulminant clonal expansion of large granular lymphocytes. Characterization of their morphology, phenotype, genotype, and function. Cancer 62: 1918-1927, 1988.

 

5. Miwa H, Nosaka T, Kita K, Ohno T, Matsuoka N, Shirakawa S, Arita Y, Doi S, Nishikori M, Honjo T, Hatanaka M. Immunogenotypes of lymphoid malignancies; the rearrangement of the T cell receptor b chain gene can occur before the g chain gene rearrangement. Jpn J Cancer Res 79: 484-490, 1988.

 

6. Nosaka T, Siomi H, Adachi Y, Ishibashi M, Kubota S, Maki M, Hatanaka M. Nucleolar targeting signal of human T-cell leukemia virus type I rex-encoded protein is essential for cytoplasmic accumulation of unspliced viral mRNA. Proc Natl Acad Sci USA 86: 9798-9802, 1989.

 

7. Nosaka T, Kita K, Miwa H, Kawakami K, Ikeda T, Ohno T, Matsuoka N, Arita Y, Doi S, Nishikori M, Matsuda F, Lee KH, Shirakawa S, Honjo T, Hatanaka M. Cross-lineage gene rearrangements of human leukemic -precursor cells occur frequently with V-DJ rearrangements of IgH genes. Blood 74: 361-368, 1989.

 

8. Kamesaki H, Fukuhara S, Uchino H, Nosaka T. A new hypothesis on the cellular origin of Reed-Sternberg and Hodgkin cells based on the immunological and molecular genetic analysis of the KM-H2 line. Recent Results in Cancer Res 117: 83-90, 1989.

 

9. Miwa H, Kita K, Nosaka T, Kawakami K, Ikeda T, Shirakawa S. A mechanism for cross-lineage gene rearrangements in B-cell neoplasm. Acta Haematol Jpn 52: 1442-1450, 1989.

 

10. Tanaka A, Takahashi C, Yamaoka S, Nosaka T, Maki M, Hatanaka M. Oncogenic transformation by the tax gene of human T-cell leukemia virus type I in vitro. Proc Natl Acad Sci USA 87: 1071-1075, 1990.

 

11. Kanamori H, Suzuki N, Siomi H, Nosaka T, Sato A, Sabe H, Hatanaka M, Honjo T. HTLV-I p27rex stabilizes human interleukin-2 receptor a-chain mRNA. EMBO J 9: 4161-4166, 1990.

 

12. Adachi Y, Nosaka T, Hatanaka M. Protein kinase inhibitor H-7 blocks accumulation of unspliced mRNA of human T-cell leukemia virus type I (HTLV-I). Biochem Biophys Res Commun 169: 469-475, 1990.

 

13. Ikeda T, Kita K, Miwa H, Kawakami K, Anazawa H, Ohno T, Nosaka T, Hatanaka M, Honjo T, Shirakawa S. Genetic heterogeneity in blast crisis of chronic myelocytic leukemia. Leukemia Res 14: 195-201, 1990.

 

14. Arita Y, Kita K, Nasu K, Doi S, Fukuhara S, Nishikori M, Miwa H, Tatsumi E, Nosaka T, Hatanaka M, Uchino H. Frequent expression of myeloid antigen (CD13) on immature T cells in culture. Acta Haematol Jpn 53: 21-34, 1990.

 

15. Kubota S, Nosaka T, Cullen BR, Maki M, Hatanaka M. Effects of chimeric mutants of human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex on nucleolar targeting signals. J Virol 65: 2452-2456, 1991.

 

16. White KN, Nosaka T, Kanamori H, Hatanka M, Honjo T. The nucleolar localisation signal of the HTLV-I protein p27rex is important for stabilisation of IL-2 receptor a  subunit mRNA by p27rex. Biochem Biophys Res Commun 175: 98-103, 1991.

 

17. Kubota S, Nosaka T, Furuta R, Maki M, Hatanaka M. Functional conversion from HIV-1 Rev to HTLV-1 Rex by mutation. Biochem Biophys Res Commun 178: 1226-1232, 1991.

 

18. Hatabu H, Kasagi K, Iida Y, Nosaka T, Misaki T, Hidaka A, Tokuda Y, Endo K, Mori T, Lee K, Tsuboi K, Hatanaka M, Konishi J. Induction of c-fos and c-myc mRNA expression by immunoglobulin G from patients with Graves disease in thyrotrophin-dependent rat thyroid cell line (FRTL5). Clin Endocrinol 34: 349-356, 1991.

 

19. Adachi Y, Copeland TD, Takahashi C, Nosaka T, Ahmed A, Oroszlan S, Hatanaka M. Phosphorylation of the Rex protein of human T-cell leukemia virus type I. J Biol Chem 267: 21977-21981, 1992.

 

20. Sakurai M, Yamaoka S, Nosaka T, Akayama M, Tanaka A, Maki M, Hatanaka M. Transforming activity and the level of Tax protein: Effect of one point mutation in HTLV-I tax gene. Int J Cancer 52: 323-328, 1992.

 

21. Miyazaki Y, Takamatsu T, Nosaka T, Fujita S, Hatanaka M. Intranuclear topological distribution of HIV-1 trans-activators. FEBS Lett 305: 1-5, 1992.

 

22. Miwa H, Kita K, Nosaka T, Ikeda T, Kawakami K, Anazawa H, Hoshino K, Ohno T, Honjo T, Hatanaka M, Shirakawa S. Maturational stage specific immunoglobulin heavy chain gene rearrangements, determined by D and D upstream region gene structures. Leukemia Res 16: 861-871, 1992.

 

23. Kawakami K, Kita K, Miwa H, Ikeda T, Nishii K, Masuya M, Morita N, Ohno T, Tanaka I, Nosaka T, Honjo T, Shirakawa S. Rearrangement patterns of immunoglobulin heavy chain (IgH) and light chain genes in acute lymphoblastic leukemia and chronic myelocytic leukemia lymphoid crisis cells showing oligoclonal IgH gene rearrangements. Int J Hematol 55: 61-69, 1992.

 

24. Nosaka T, Takamatsu T, Miyazaki Y, Sano K, Sato A, Kubota S, Sakurai M, Ariumi Y, Nakai M, Fujita S, Hatanaka M. Cytotoxic activity of rev protein of human immunodeficiency virus type 1 by nucleolar dysfunction. Exp Cell Res 209: 89-102, 1993.

 

25. Nosaka T, Ariumi Y, Sakurai M, Takeuchi R, Hatanaka M. Novel internal promoter/enhancer of HTLV-I for Tax expression. Nucl Acids Res 21: 5124-5129, 1993.

 

26. Nakajima T, Aono H, Hasunuma T, Yamamoto K, Maruyama I, Nosaka T, Hatanaka M, Nishioka K. Overgrowth of human synovial cells driven by the human T cell leukemia virus type I tax gene. J Clin Invest 92: 186-193, 1993.

 

27. Takano E, Nosaka T, Lee WJ, Nakamura K, Takahashi T, Funaki M, Okada H, Hatanaka M, Maki M. Molecular diversity of calpastatin in human erythroid cells. Arch Biochem Biophys 303: 349-354, 1993.

 

28. Tanabe S, Fukuhara S, Yoneda T, Ohmori K, Nosaka T, Hatanaka M, Okuma M. Characterization of a novel biphenotypic leukemia cell line, TA-1, with myeloperoxidase and inducible cytoplasmic m chain: Altered rearrangement patterns of antigen receptor genes. Int J Hematol 57: 229-243, 1993.

 

29. Ueba T, Nosaka T, Takahashi JA, Shibata F, Florkiewicz RZ, Vogelstein B, Oda Y, Kikuchi H, Hatanaka M. Transcriptional regulation of basic fibroblast growth factor gene by p53 in human glioblastoma and hepatocellular carcinoma cells. Proc Natl Acad Sci USA 91: 9009-9013, 1994.

 

30. Nosaka T, Miyazaki Y, Takamatsu T, Sano K, Nakai M, Fujita S, Martin TE, Hatanaka M. The post-transcriptional regulator Rex of the human T-cell leukemia virus type I is present as nucleolar speckles in infected cells. Exp Cell Res 219: 122-129, 1995.

 

31. Miyazaki Y, Takamatsu T, Nosaka T, Fujita S, Martin TE, Hatanaka M. The cytotoxicity of human immunodeficiency virus type 1 Rev: Implications for its interaction with the nucleolar protein B23. Exp Cell Res 219: 93-101, 1995.

 

32. Nosaka T, van Deursen JMA, Tripp RA, Thierfelder WE, Witthuhn BA, McMickle AP, Doherty PC, Grosveld GC, Ihle JN. Defective lymphoid development in mice lacking JAK3. Science 270: 800-802, 1995.

 

33. Quelle FW, Wang D, Nosaka T, Thierfelder WE, Stravopodis D, Weinstein Y, Ihle JN. Erythropoietin induces activation of Stat5 through association with specific tyrosines on the receptor that are not required for a mitogenic response. Mol Cell Biol 16: 1622-1631, 1996.

 

34. Shimoda K, van Deursen J, Sangster MY, Sarawar SR, Carson RT, Tripp RA, Chu C, Quelle FW, Nosaka T, Vignali DAA, Doherty PC, Grosveld G, Paul WE, Ihle JN. Lack of interleukin-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene. Nature 380: 630-633, 1996.

 

35. Miyazaki Y, Nosaka T, Hatanaka M. The post-transcriptional regulator Rev of HIV: Implications for its interaction with the nucleolar protein B23. Biochimie 78: 1081-1086, 1996.

 

36. Ariumi Y, Copeland TD, Nosaka T, Hatanaka M. HIRF: a novel nuclear factor that binds to the human T-cell leukemia virus type I internal regulatory element (HIRE). Leukemia 11 Suppl 3: 29-31, 1997. 

 

37. Sohn SJ, Forbush KA, Nguyen N, Witthuhn B, Nosaka T, Ihle JN, Perlmutter RM. Requirement for Jak3 in mature T-cells: Its role in regulation of T cell homeostasis. J Immunol 160: 2130-2138, 1998.

 

38. Onishi M, Nosaka T, Misawa K, Mui ALF, Gorman D, McMahon M, Miyajima A, Kitamura T. Identification and characterization of a constitutively active STAT5 mutant that promotes cell proliferation. Mol Cell Biol 18: 3871-3879, 1998.

 

39. Morikawa Y, Nishida H, Misawa K, Nosaka T, Miyajima A, Senba E, Kitamura T.  Induction of synaptosomal-associated protein-23 kd (SNAP-23) by various cytokines. Blood 92: 129-135, 1998.

 

40. Habu K, Nakayama-Yamada J, Asano M, Saijo S, Itagaki K, Horai R, Yamamoto H, Sekiguchi T, Nosaka T, Hatanaka M, Iwakura Y. The human T cell leukemia virus type I-tax gene is responsible for the development of both inflammatory polyarthropathy resembling rheumatoid arthritis and noninflammatory ankylotic arthropathy in transgenic mice. J Immunol 162: 2956-2963, 1999.

 

41. Brown MP*, Nosaka T*, Tripp RA, Brooks J, van Deursen JMA, Brenner MK, Doherty PC, Ihle JN. Reconstitution of early lymphoid proliferation and immune function in Jak3-deficient mice by interleukin-3.  Blood 94: 1906-1914, 1999 (*Equal first authors).

 

42. Nosaka T, Kawashima T, Misawa K, Ikuta K, Mui AL-F, Kitamura T. STAT5 as a molecular regulator of proliferation, differentiation and apoptosis in hematopoietic cells. EMBO J 18: 4754-4765, 1999.

 

43. Yamada K, Ariyoshi K, Onishi M, Miyajima A, Hayakawa F, Towatari M, Saito H, Oka Y, Asano S, Nosaka T, Kitamura T. Constitutively active STAT5A and STAT5B in vitro and in vivo: mutation of STAT5 is not a frequent cause of leukemogenesis. Int J Hematol 71: 46-54, 2000.

 

44. Fujio K, Nosaka T, Kojima T, Kawashima T, Yahara T, Copeland NG, Gilbert DJ, Jenkins NA, Yamamoto K, Nishimura T, Kitamura T. Molecular cloning of a novel type I cytokine receptor similar to the common gamma chain. Blood 95: 2204-2211, 2000.

 

45. Misawa K, Nosaka T, Morita S, Kaneko A, Nakahata T, Asano S, Kitamura T.  A method to identify cDNAs based on localization of green fluorescent protein fusion products. Proc Natl Acad Sci USA 97: 3062-3066, 2000.

 

46. Ariyoshi K, Nosaka T, Yamada K, Onishi M, Oka Y, Miyajima A, Kitamura T. Constitutive activation of STAT5 by a point mutation in the SH2 domain.  J Biol Chem 275; 24407-24413, 2000.

 

47. Misawa K, Nosaka T, Kojima T, Hirai M, Kitamura T. Molecular cloning and characterization of a mouse homolog of human TNFSF14, a member of the TNF superfamily. Cytogenet Cell Genet 89: 89-91, 2000.

 

48. Kawashima T, Hirose K, Satoh T, Kaneko A, Ikeda Y, Kaziro Y, Nosaka T, Kitamura T. MgcRacGAP is involved in the control of growth and differentiation of hematopoietic cells. Blood 96: 2116-2124, 2000.

 

49. Fujio K, Misaki Y, Setoguchi K, Morita S, Kawahata K, Kato I, Nosaka T, Yamamoto K, Kitamura T. Functional reconstitution of class II MHC-restricted T cell immunity mediated by retroviral transfer of the ab TCR complex. J Immunol 165: 528-532, 2000.

 

50. Sugiyama T, Kumagai H, Morikawa Y, Wada Y, Sugiyama A, Yasuda K, Yokoi N, Tamura S, Kojima T, Nosaka T, Senba E, Kimura S, Kadowaki T, Kodama T, Kitamura T. A novel low-density lipoprotein receptor-related protein mediating cellular uptake of apolipoprotein E-enriched b-VLDL in vitro. Biochemistry 39: 15817-15825, 2000.

 

51. Hirose K, Kawashima T, Iwamoto I, Nosaka T, Kitamura T. MgcRacGAP is involved in cytokinesis through associating with mitotic spindle and midbody.  J Biol Chem 276: 5821-5828, 2001.

 

52. Kawashima T, Murata K, Akira S, Tonozuka Y, Minoshima Y, Feng S, Kumagai H, Tsuruga H, Ikeda Y, Asano S, Nosaka T, Kitamura T. STAT5 induces macrophage differentiation of M1 leukemia cells through activation of IL-6 production mediated by NF-kB p65. J Immunol 167: 3652-3660, 2001.

 

53. Tonozuka Y, Fujio K, Sugiyama T, Nosaka T, Hirai M, Kitamura T. Molecular cloning of a human novel type I cytokine receptor related to d1/TSLPR. Cytogenet Cell Genet 93: 23-25, 2001.

 

54. Tulin EE, Onoda N, Maeda M, Hasegawa M, Nosaka T, Nomura H, Asano S, Kitamura T. A novel secreted form of immune suppressor factor with high homology to vacuolar ATPases identified by a forward genetic approach of functional screening based on cell proliferation. J Biol Chem 276: 27519-27526, 2001.

 

55. Tulin EE, Onoda N, Hasegawa M, Nosaka T, Nomura H, Kitamura T. Genetic approach and phenotype-based complementation screening for identification of stromal cell-derived proteins involved in cell proliferation. Exp Cell Res 272: 23-31, 2002.

 

56. Nosaka T, Kitamuta T. Pim-1 expression is sufficient to induce cytokine independence in murine hematopoietic cells, but is dispensable for BCR-ABL-mediated transformation. Exp Hematol 30: 697-702, 2002.

 

57. Nosaka T, Morita S, Kitamura H, Nakajima H, Shibata F, Morikawa Y, Kataoka Y, Ebihara Y, Kawashima T, Itoh T, Ozaki K, Senba E, Tsuji K, Makishima F, Yoshida N, Kitamura T. Mammalian Twisted gastrulation is essential for skeleto-lymphogenesis. Mol Cell Biol 23: 2969-2980, 2003.

 

58. Minoshima Y, Kawashima T, Hirose K, Tonozuka Y, Kawajiri A, Bao YC, Deng X,  Tatsuka M, Narumiya S, May WS Jr, Nosaka T, Semba K, Inoue T, Satoh T, Inagaki M, Kitamura T. Phosphorylation by Aurora B converts MgcRacGAP to a RhoGAP during cytokinesis. Dev Cell 4: 549-560, 2003.

 

59. Murata K, Kumagai H, Kawashima T, Tamitsu K, Irie M, Nakajima H, Suzu S, Shibuya M, Kamihira S, Nosaka T, Asano S, Kitamura T. Selective cytotoxic mechanism of GTP-14564, a novel tyrosine kinase inhibitor in leukemia cells expressing a constitutively active Fms-like tyrosine kinase 3 (FLT3). J Biol Chem 278: 32892-32898, 2003.

 

60. Ikeda Y, Imai Y, Kumagai H, Nosaka T, Morikawa Y, Hisaoka T, Manabe I, Maemura K, Nakaoka T, Imamura T, Miyazono K, Komuro I, Nagai R, Kitamura T. Vasorin, a transforming growth factor b-binding protein expressed in vascular smooth muscle cells, modulates the arterial response to injury in vivo.  Proc Natl Acad Sci USA 101: 10732-10737, 2004.

 

61. Tonozuka Y, Minoshima Y, Bao YC, Moon Y, Tsubono Y, Hatori T, Nakajima H, Nosaka T, Kawashima T, Kitamura T. A GTPase-activating protein binds STAT3 and is required for IL-6-induced STAT3 activation and for differentiation of a leukemic cell line. Blood 104: 3550-3557, 2004.

 

62. Ono R, Nakajima H, Ozaki K, Kumagai H, Kawashima T, Taki T, Kitamura T, Hayashi Y, Nosaka T. Dimerization of MLL fusion proteins and FLT3 activation synergize to induce multiple lineage leukemogenesis. J Clin Invest 115: 919-929, 2005.

 

63. Urano A, Endoh M, Wada T, Morikawa Y, Itoh M, Kataoka Y, Taki T, Akazawa H, Nakajima H, Komuro I, Yoshida N, Hayashi Y, Handa H, Kitamura T, Nosaka T. Infertility with defective spermiogenesis in mice lacking AF5q31, the target of chromosomal translocation in human infant leukemia. Mol Cell Biol 25: 6834-6845, 2005.

 

64. Ono R, Ihara M, Nakajima H, Ozaki K, Kataoka-Fujiwara Y, Taki T, Nagata K, Inagaki M, Yoshida N, Kitamura T, Hayashi Y, Kinoshita M, Nosaka T. Disruption of Sept6, a fusion partner gene of MLL, does not affect ontogeny, leukemogenesis induced by MLL-SEPT6, or phenotype induced by the loss of Sept4. Mol Cell Biol 25: 10965-10978, 2005.

 

65. Ozaki K, Hishiya A, Hatanaka K, Nakajima H, Wang G, Hwu P, Kitamura T, Ozawa K, Leonard WJ, Nosaka T. Overexpression of Interleukin 21 induces expansion of hematopoietic progenitor cells. Int J Hematol 84: 224-230, 2006.

 

66. Kawashima T, Bao YC, Moon Y, Tonozuka Y, Minoshima Y, Hatori T, Kiyono M, Nosaka T, Nakajima H, Williams DA, Kitamura T. Rac 1 and a GTPase-activating protein, MgcRacGAP, are required for nuclear translocation of STAT transcription factors. J Cell Biol 175: 937-946, 2006.

 

67. Lu Y, Kitaura J, Oki T, Komeno Y, Ozaki K, Kiyono M, Kumagai H, Nakajima H, Nosaka T, Aburatani H, Kitamura T. Identification of TSC-22 as a potential tumor suppressor that is upregulated by Flt3-D835V but not Flt3-ITD. Leukemia 21: 2246-2257, 2007.

 

68. Watanabe-Okochi N, Kitaura J, Ono R, Harada H, Harada Y, Komeno Y, Nakajima H, Nosaka T , Inaba T, Kitamura T. AML1 mutations induced MDS and MDS/AML in a mouse BMT model. Blood 111: 4297-4308. 2008.

 

69. Nishio M, Ohtsuka J, Tsurudome M, Nosaka T, Kolakofsky D. Human parainfluenza virus type 2 V protein inhibits genome replication by binding to the L protein; a possible role in promoting viral fitness. J Virol 82: 6130-6138, 2008.

 

70. Hiwatari M, Ono R, Taki T, Hishiya A, Ishii E, Kitamura T, Hayashi Y, Nosaka T. Novel gain-of-function mutation in the extracellular domain of the PDGFRA gene in infant acute lymphoblastic leukemia with t(4;11)(q21;q23). Leukemia 22: 2279-2280, 2008.

 

71. Ikeya M, Nosaka T, Fukushima K, Kawada M, Furuta Y, Kitamura T, Sasai Y. Twisted gastrulation mutation suppresses skeletal defect phenotypes in Crossveinless 2 mutant mice. Mech Dev 125: 832-842, 2008.

 

72. Matsushita H, Nakajima H, Nakamura Y, Tsukamoto H, Tanaka Y, Jin G, Yabe M, Asai S, Ono R, Nosaka T, Sugita K, Morimoto A, Hayashi Y, Hotta T, Ando K, Miyachi H. C/EBPa and C/EBPe induce the monocytic differentiation of myelomonocytic cells with the MLL-chimeric fusion gene. Oncogene 27: 6749-6760, 2008.

 

73. Kawashima T, Bao YC, Minoshima Y, Nomura Y, Hatori T, Hori T, Fukagawa T, Fukada T, Takahashi N, Nosaka T, Inoue M, Sato T, Kukimoto-Niino M, Shirouzu, M, Yokoyama S, Kitamura T. A Rac GTPase activating protein MgcRacGAP is an NLS-containing nuclear chaperone in the activation of STAT transcription factors. Mol Cell Biol 29: 1796-1813, 2009.

 

74. Watanabe-Okochi N, Oki T, Komeno Y, Kato N, Yuji K, Ono R, Harada Y, Harada H, Hayashi Y, Nakajima H, Nosaka T , Kitaura J, Kitamura T. Possible involvement of RasGRP4 in leukemogenesis. Int J Hematol 89: 470-481, 2009.

 

75. Ono R, Kumagai H, Nakajima H, Hishiya A, Taki T, Horikawa K, Takatsu K, Satoh T, Hayashi Y, Kitamura T, Nosaka T . Mixed-lineage-leukemia (MLL) fusion protein collaborates with Ras to induce acute leukemia through aberrant Hox expression and Raf activation.  Leukemia 23: 2197-2209, 2009.

 

76. Jin G, Matsushita H, AsaiS, Tsukamoto H, Ono R, Nosaka T , Yahata T, Takahashi S, Miyachi H. FLT3-ITD induces ara-C resistance in myeloid leukemic cells through the repression of the ENT1 expression. Biochem Biophys Res Commun 390, 1001-1006, 2009.

 

77. Ikeya M, Fukushima K, Kawada M, Onishi S, Furuta Y, Yonemura S, Kitamura T, Nosaka T, Sasai Y. Cv2, functioning as a pro-BMP factor via twisted gastrulation, is required for early development of nephron precursors. Dev Biol 337: 405-414, 2010.

 

78. Minobe K, Ono R, Matsumine A, Shibata-Minoshima F, Izawa K, Oki T, Kitaura J, Iino T, Takita J, Iwamoto S, Hori H, Komada Y, Uchida A, Hayashi Y, Kitamura T, Nosaka T. Expression of ADAMTS4 in Ewing’s sarcoma. Int J Oncol 37: 569-581, 2010.

 

79. Nishio M, Tsurudome M, Garcin D, Komada H, Ito M, Le Mercier P, Nosaka T, Kolakofsky D. Human parainfluenza virus type 2 L protein regions required for interaction with other viral proteins and mRNA capping. J Virol 85: 725-732, 2011.

 

80. Tsurudome M, Ito M, Nishio M, Nakahashi M, Kawano M, Komada H, Nosaka T, Ito Y. Identification of domains on the fusion (F) protein trimer that influence the hemagglutinin-neuraminidase specificity of the F protein in mediating cell-cell fusion. J Virol 85: 3153-3161, 2011.

 

81. Suzuki K, Ono R, Ohishi K, Masuya M, Kataoka I, Liu B, Nakamori Y, Ino K, Monma F, Hamada H, Kitamura T, Katayama N, Nosaka T. IKAROS isoform 6 enhances BCR-ABL1-mediated proliferation of human CD34+hematopoietic cells on stromal cells. Int J Oncol 40: 53-62, 2012.

 

82. Komori T, Doi A, Nosaka T, Furuta H, Akamizu T, Kitamura T, Senba, E, Morikawa Y. Regulation of AMP-activated Protein Kinase Signaling by AFF4, a Member of the AF4 (ALL1-fused Gene from Chromosome 4) Family of Transcription Factors, in Hypothalamic Neurons. J Biol Chem 287: 19985-19996, 2012.

 

83. Nagai Y, Iwade Y, Hayakawa E, Nakano M, Sakai T, Tanuma M, Katayama M, Nosaka T, Yamaguchi T. Molecular Genotyping of Mycobacterium tuberculosis in Mie Prefecture, Japan, Using Variable Numbers of Tandem Repeats Analysis. Jpn J Infect Dis 65: 341-344, 2012.

 

84. Liu B, Ohishi K, Orito Y, Nakamori Y, Nishikawa H, Ino K, Suzuki K, Matsumoto T, Masuya M, Hamada H, Mineno J, Ono R, Nosaka T , Shiku H, Katayama N. Manipulation of human early T lymphopoiesis by coculture on human bone marrow stromal cells: Potential utility for adoptive immunotherapy. Exp Hematol 41: 367-376, 2013.

 

85. Tsurudome M, Nakahashi M, Matsushima Y,Ito M, Nishio M, Kawano M, Komada H, Nosaka T. Full conversion of the hemagglutinin-neuraminidase specificity of the parainfluenzavirus 5 fusion protein by replacement of 21 amino acids in its head region with those of the simian virus 41 fusion protein. J Virol 87: 8342-8350, 2013.

 

86. Ono R, Masuya M, Nakajima H, Enomoto Y, Miyata E, Nakamura A, Ishii S, Suzuki K, Shibata-Minoshima F, Katayama N, Kitamura T, Nosaka T. Plzf drives MLL-fusion-mediated leukemogenesis specifically in long term hematopoietic stem cells. Blood 122: 1271-1283, 2013.

 

87. Kitagawa H, Kawano M; Yamanaka K, Kakeda M, Tsuda K, Inada H, Yoneda M, Sakaguchi T, Nigi A, Nishimura K, Komada H, Tsurudome M, Yasutomi Y, Nosaka T , Mizutani H. Intranasally administered Antigen 85B gene vaccine in non-replicating human Parainfluenza type 2 virus vector ameliorates mouse atopic dermatitis. PLoS One 2013 Jul 3; 8(7): e66614.

 

88. Hara K, Fukumura M, Ohtsuka J, Kawano M, Nosaka T. Human Parainfluenza virus type 2 vector induces dendritic cell maturation without viral RNA replication/transcription. Hum Gene Ther 24: 683-691, 2013.

 

89. Shimozawa N, Ono R, Shimada M, Shibata H, Takahashi I, Inada H, Takada T, Nosaka T, Yasutomi Y. Cynomolgus monkey induced pluripotent stem cells established by using exogenous genes derived from the same monkey species. Differentiation 85: 131-139, 2013.

 

90. Nagai Y, Iwade Y, Hayakawa E, Nakano M, Sakai T, Mitarai S, Katayama M, Nosaka T, Yamaguchi T. High resolution melting curve assay for rapid detection of drug-resistant Mycobacterium tuberculosis. J Infect Chemother 19: 1116-1125, 2013.

 

91. Watanabe K, Matsubara A, Kawano M, Mizuno S, Okamura T, Tsujimura Y, Inada H, Nosaka T, Matsuo K, Yasutomi Y. Recombinant Ag85B vaccine by taking advantage of characteristics of human parainfluenza type 2 virus vector showed Mycobacteria-specific immune responses by intranasal immunization. Vaccine 32: 1727–1735, 2014.

 

92. Ohtsuka J, Fukumura M, Tsurudome M, Hara K, Nishio M, Kawano M, Nosaka T. Vero/BC-F: an efficient packaging cell line stably expressing F protein to generate single round-infectious human parainfluenza virus type 2 vector. Gene Ther 21:775-784, 2014.

 

93. Tsurudome M, Ito M, Ohtsuka J, Hara K, Komada H, Nishio M, Nosaka T. The fusion protein specificity of the parainfluenza virus hemagglutinin-neuraminidase protein is not solely defined by the primary structure of its stalk domain. J Virol 89: 12374-12387, 2015.

 

94. Kitamura T, Okochi-Watanabe N, Enomoto Y, Nakahara F, Oki T, Komeno Y, Kato N, Doki N, Uchida T, Kagiyama Y, Togami K, Kawabata KC, Nishimura K, Hayashi Y, Nagase R, Saika M, Fukushima T, Asada S, Fujino T, Izawa Y, Horikawa S, Fukuyama T, Tanaka Y, Ono R, Goyama S, Nosaka T, Kitaura J, Inoue D. Novel working hypothesis for pathogenesis of hematological malignancies; Combination of mutations-induced cellular phenotypes determines the disease (cMIP-DD). J Biochem 159: 17-25, 2016.

 

95. Kobayashi K, Yamaguchi M, Miyazaki K, Imai H, Yokoe K, Ono R, Nosaka T, Katayama N. Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B-cell lymphoma cells and their association with clinical features. Cancer Med 5: 1802-1809, 2016.

 

96. Yamanaka K, Nakanishi T, Isono K, Hasegawa C, Inada Y, Mizutani K, Matsushima Y, Okada K, Mabuchi T, Kondo M, Yamagiwa A, Kakeda M, Habe K, Nosaka T, Gabazza EC, Yamazaki H, Mizutani H, Kawano M. Restrictive interleukin-10 induction by an innocuous Parainfluenza virus vector ameliorates nasal allergy. J Allergy Clin Immunol 139: 682-686.e7, 2017.

 

97. Takeuchi, T, Yamaguchi M, Kobayashi K, Miyazaki K, Tawara I, Imai H, Ono R, Nosaka T, Tanaka K, Katayama N. MYD88, CD79B, and CARD11 gene mutations in CD5-positive diffuse large B-cell lymphoma. Cancer 123: 1166-1173, 2017.

 

98. Ono R. Masuya M, Ishii S, Katayama N, Nosaka T. Eya2, a target activated by Plzf, is critical for PLZF-RARA-induced leukemogenesis. Mol Cell Biol 37:e00585-16, 2017.

 

99. Tsurudome M, Ohtsuka J, Ito M, Nishio M, Nosaka T. The hemagglutinin-neuraminidase (HN) head domain and the fusion (F) protein stalk domain of the parainfluenza viruses affect the specificity of the HN-F interaction. Front Microbiol 9: 391, 2018.

 

100. Nagatake T, Suzuki H, Hirata S, Matsumoto N, Wada Y, Morimoto S, Nasu A, Shimojou M, Kawano M, Ogami K, Tsujimura Y, Kuroda E, Iijima N, Hosomi K, Ishii KJ, Nosaka T, Yasutomi Y, Kunisawa J. Immunological association of inducible bronchus-associated lymphoid tissue organogenesis in Ag85B-rHPIV2 vaccine-induced anti-tuberculosis mucosal immune responses in mice. Int Immunol 30: 471-481, 2018.

 

101. Maharjan BD, Ono R, Nosaka T. Eya2 is critical for the E2A-HLF-mediated immortalization of mouse hematopoietic stem/progenitor cells. Int J Oncol 54: 981-990, 2019.

 

102. Ohtsuka J, Matsumoto Y, Ohta K, Fukumura M, Tsurudome M, Nosaka T, Nishio M. Nucleocytoplasmic shuttling of the human parainfluenza virus type 2 phosphoprotein. Virology 528: 54-63, 2019.

 

103. Ohtsuka J, Fukumura M, Furuyama W, Wang S, Hara K, Maeda M, Tsurudome M, Miyamoto H, Kaito A, Tsuda N, Kataoka Y, Mizoguchi A, Takada A, Nosaka T. A versatile platform technology for recombinant vaccines using non-propagative human parainfluenza virus type 2 vector. Sci Rep 9: 12901, 2019.

 

104. D'Alessandro-Gabazza CN, Kobayashi T, Yasuma T, Toda M, Kim H, Fujimoto H, Hataji O, Takeshita A, Nishihama K, Okano T, Okano Y, Nishii Y, Tomaru A, Fujiwara K, D'Alessandro VF, Abdel-Hamid AM, Ren Y, Pereira GV, Wright CL, Hernandez A, Fields CJ, Yau PM, Wang S, Mizoguchi A, Fukumura M, Ohtsuka J, Nosaka T, Kataoka K, Kondoh Y, Wu J, Kawagishi H, Yano Y, Mackie RI, Cann I, Gabazza EC. A Staphylococcus pro-apoptotic peptide induces acute exacerbation of pulmonary fibrosis. Nat Commun 11:1539, 2020.

 

105. Sawaki A, Miyazaki K, Yamaguchi M, Takeuchi T, Kobayashi K, Imai H, Tawara I, Ono R, Nosaka T, Katayama N. Genetic polymorphisms and vincristine-induced peripheral neuropathy in patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy. Int J Hematol 111: 686-691, 2020.

 

106. Ono R, Masuya M, Inoue N, Shinmei M, Ishii S, Maegawa Y, Mahrjan BD, Katayama N, Nosaka T. Tet1 is not required for myeloid leukemogenesis by MLL-ENL in novel mouse models. PLosONE 16(3): e0248425, 2021.

 

107. Ohtsuka J, Imai M, Fukumura M, Maeda M, Eguchi A, Ono R, Maemura T, Ito M, Yamayoshi S, Kataoka Y, Kawaoka Y, Nosaka T. Non-propagative human parainfluenza virus type 2 nasal vaccine robustly protects the upper and lower airways against SARS-CoV-2. iScience 24: 103379, 2021.

 

 

                  Book Chapters and Review Articles

 

1. Kita K, Miwa H, Nosaka T, Ohno T, Nasu K, Nanba K, Shirakawa S. Molecular genetic analysis of lymphoid malignancies. In: Hanaoka M et al., eds. Lymphoid Malignancy, Immunocytology and Cytogenetics. New York: Field & Wood Med Pub Inc. pp3-13, 1990.

 

2. Ihle JN, Nosaka T, Thierfelder W, Quelle FW, Shimoda K. Jaks and Stats in cytokine signaling. Stem Cells 15 Suppl 1: 105-112, 1997.

 

3. Onishi M, Nosaka T, Kitamura T. Cytokine Receptors: Structure and signal transduction. Int Rev Immunol 16: 617-634, 1998.

 

4. Nosaka T, Onishi M, Kawashima T, Yamada K, Misawa K, Ariyoshi K, Towatari M, Saito H, Tani K, Asano S, Miyajima A, Kitamura T. Identification and characterization of constitutively active STAT5. In: Abraham NG et al., eds. Molecular Biology of Hematopoiesis 6. New York: Kluwer Academic/Plenum Publishers. pp277-287, 1999.

 

5. Nosaka T, Kitamura T. Janus kinases (JAKs) and signal transducers and activators of transcription (STATs)  in hematopoietic cells. Int J Hematol  71: 309-319, 2000.

 

6. Kitamura T, Kawashima T, Minoshima Y, Tonozuka Y, Hirose K, Nosaka T. Role of MgcRacGAP/Cyk4 as a regulator of the small GTPase Rho family in cytokinesis and cell differentiation. Cell Struct Funct 26: 645-651, 2001.

 

7. Nosaka T. Jaks and normal hematopoiesis. In: Ward AC ed. The Jak-Stat Pathway in Hematopoiesis and Disease. Georgetown: Landes Bioscience Publishers (Eurekah. com., Austin) pp1-9, 2002.

 

8. Kitamura T, Koshino Y, Shibata F, Oki T, Nakajima H, Nosaka T, Kumagai H. Retrovirus-mediated gene transfer and expression cloning: Powerful tools in functional genomics. Exp Hematol 31: 1007-1014, 2003.

 

9. Ono R, Nosaka T, Hayashi Y. Roles of a trithorax group gene, MLL, in hematopoiesis. Int J Hematol 81: 288-293, 2005.

 

 

                            日本語論文、著書

 

1. 宇野伸郎、野阪哲哉、内山哲、川上恵基、星野賢一郎、森美貴、堀田安則、太田千鶴子、小林透、北堅吉、白川茂. 造血器悪性疾患に合併した重症感染症に対する Amikacin Cefoxitin の併用療法. Jpn J Antibiotics 40(3): 469-475, 1987.

 

2. 三輪啓志、松岡信良、野阪哲哉、北堅吉、白川茂. 悪性リンパ腫診断における分子遺伝学的手法の有用性と限界. 日本網内系学会会誌 29(2): 127-135, 1989.

 

3. 野阪哲哉. 悪性リンパ腫の病因:ウイルス. Pharma Medica 11(2): 15-19, 1993.

 

4. 野阪哲哉. アンチセンス、env、腫瘍壊死因子、DNA修飾酵素、リンフォトキシン. In: 永田和宏、長野敬、宮坂信之、宮坂昌之 編集. 分子生物学・免疫学キーワード辞典 東京 医学書院 pp27-28, 100, 231-232, 296, 482. 1994.

 

5. 宮崎之男、野阪哲哉、畑中正一.  3 蛍光顕微鏡モードによる応用、4. 細胞内構造の観察への応用、 5) 核小体とウイルス. In: 石川春律、高松哲郎 編集. 新しい光学顕微鏡 第二巻 共焦点レーザ顕微鏡の医学・生物学への応用 東京 学際企画 pp111-115, 1995.

 

6. 野阪哲哉. JAK3 欠損マウスとリンパ球. 血液・腫瘍科 34(1): 48-55, 1997.

 

7. 野阪哲哉.  JAK3 SCID. 医学のあゆみ 180(13): 842-845, 1997. 

 

8. 野阪哲哉、北村俊雄.  STAT 遺伝子の変異と機能変化. 血液・腫瘍科 40(6): 541-550, 2000.

 

9. 野阪哲哉、北村俊雄. 造血疾患と転写因子. 組織培養工学 特集 転写因子の新しい展開 26(13): 503-506, 2000.

 

10. 野阪哲哉. アダプター蛋白、アンチセンスRNA アンチセンス鎖、アンチセンスDNA、アンチセンス法、修飾(DNAの)、DNAグリコシラーゼ. In: 伊藤正男、井村裕夫、高久史磨 編集. 医学大辞典 東京 医学書院 pp28, 81, 1111, 1682. 2003.

 

11. 野阪哲哉. アンチセンス、envGrb2JNK/p38カスケード、Sos (son of sevenless)DNA修飾酵素、DNAリガーゼ. In: 永田和宏、宮坂昌之、宮坂信之、山本一彦 編集. 分子生物学・免疫学キーワード辞典 2  東京 医学書院 pp57-58, 206, 285, 417-418, 516, 555-556, 563. 2003.

 

12. 野阪哲哉.  プロテアーゼと白血病発症の意外な関係. In: News & Hot Paper Digest.  実験医学 22(1): 43-44, 2004.

 

13. 北村俊雄、野阪哲哉. 新規チロシンキナーゼ阻害剤GTP14564Flt3. マクロファージ フォーラム Mini-review  In: 今日の移植. 17(3): 416-420, 2004.

 

14. 北村俊雄、熊谷英敏、野阪哲哉. Flt3阻害剤. In: 血液病の分子標的療法〜新たな展開〜. 血液フロンティア. 14(7): 47-53(1035-1041), 2004.

 

15. 小埜良一、野阪哲哉. MLL関連白血病の分子病態. 血液・腫瘍科 52(6): 615-624, 2006.

 

16. 野阪哲哉. 造血器腫瘍マウスモデル. がん分子標的治療.6(2):25-33(101-109), 2008.

 

17. 野阪哲哉 、小埜良一. MLL融合遺伝子による白血病発症機構. 血液・腫瘍科. 61(2): 217-223, 2010.

 

18. 野阪哲哉. 血液腫瘍モデル動物の現状と展望. In: 金倉譲 編集. 造血器腫瘍学-基礎と臨床の最新研究動向- 日本臨床20124 増刊. pp159-164.

 

19. 野阪哲哉. Jak-STAT経路. In: 栗原裕基 編集. 細胞シグナル操作法. 生体の科学 66: 420-421, 2015.

 

20. 小埜良一、野阪哲哉. 血液腫瘍モデル動物の現状と展望. In: 金倉譲 編集. 造血器腫瘍学(第2版)-基礎と臨床の最新研究動向-. II. 造血器腫瘍の基礎日本臨床 78巻 増刊号3 (2020831日発行)  pp152-158.

 

 

所属学会   

日本血液学会(平成12年より評議員、平成18年より20年まで編集委員)、日本癌学会、日本ウイルス学会、American Society of HematologyAmerican Society for Microbiology

 

学術上の栄誉

1989 年度 三医会賞

1995 年度  アメリカ血液学会賞(ASH Merit Award

1996 年度 日本血液学会奨励賞

2006 年度 日本白血病研究基金 一般研究賞

2013 年度 日本白血病研究基金 一般研究賞