森 直樹 (モリ ナオキ)

Mori Naoki

写真a

職名

教授

科研費研究者番号

10220013

ホームページ

https://naokimori50.wixsite.com/mysite

現在の所属組織 【 表示 / 非表示

  • 専任   琉球大学   医学研究科   教授  

取得学位 【 表示 / 非表示

  • 産業医学大学 -  博士(医学)  その他 / その他

職歴 【 表示 / 非表示

  • 2002年04月
    -
    継続中

      琉球大学 医学研究科 教授  

研究キーワード 【 表示 / 非表示

  • HTLV-1,成人T細胞白血病/リンパ腫,転写因子,アポトーシス,分子標的療法,細胞浸潤

研究分野 【 表示 / 非表示

  • ライフサイエンス / 細胞生物学

  • ライフサイエンス / 血液、腫瘍内科学

  • ライフサイエンス / ウイルス学

主たる研究テーマ 【 表示 / 非表示

  • 天然成分による発がん予防

  • 悪性腫瘍の浸潤・転移機構

  • 悪性腫瘍の分子標的療法の開発

  • 腫瘍関連ウイルスの発がん機構

論文 【 表示 / 非表示

  • Exportin-1 is critical for cell proliferation and survival in adult T cell leukemia.

    Ishikawa C, Mori N

    Investigational new drugs ( Investigational New Drugs )  40 ( 4 ) 718 - 727   2022年08月 [ 査読有り ]

    掲載種別: 研究論文(学術雑誌)

  • FX1, a BCL6 inhibitor, reactivates BCL6 target genes and suppresses HTLV-1-infected T cells.

    Ishikawa C, Mori N

    Investigational new drugs ( Investigational New Drugs )  40 ( 2 ) 245 - 254   2022年04月 [ 査読有り ]

    掲載種別: 研究論文(学術雑誌)

     概要を見る

    Human T cell leukemia virus type 1 (HTLV-1) is responsible for adult T cell leukemia (ATL); however, molecular and cellular mechanisms underlying HTLV-1-induced leukemogenesis are unclear. BCL6 oncogene is involved in cancer progression and a preferred target of anti-cancer treatments. Here, we aimed to evaluate BCL6 expression and the effects of BCL6 inhibitor (FX1) on HTLV-1-infected T cell lines. BCL6 expression was higher in HTLV-1-infected T cell lines than that in uninfected T cell lines. BCL6 was localized mostly in the nucleus. The virus oncoprotein Tax induced BCL6 mRNA expression in T cells, whereas BCL6 knockdown reduced HTLV-1-infected T cell proliferation; thus, confirmed the association of BCL6 with cancer progression. Further, FX1 efficiently inhibited the cell growth and survival of HTLV-1-infected T cell lines in a dose- and time-dependent manner. The decreased levels of cell cycle regulatory proteins (phosphorylated retinoblastoma protein, cyclin-dependent kinase 4, cyclin D2 and c-Myc) and the increased levels of BCL6 target proteins (p21, p27 and p53) showed that FX1 arrested cell cycle at the G1 phase. Apoptosis was induced concomitantly with Bak upregulation and downregulation of survivin, Bcl-xL and Mcl-1, as well as with the activation of caspase-3, -8, -9 and poly(ADP-ribose) polymerase. FX1 also inhibited NF-κB and Akt signaling pathways. These events were because of the induction of the activity of cell cycle checkpoint proteins and relief of direct repression of the targets of cell cycle checkpoint proteins. Thus, BCL6 might be considered a novel target for ATL treatment.

  • The antipsychotic drug pimozide is effective against human T-cell leukemia virus type 1-infected T cells.

    Ishikawa C, Mori N

    European journal of pharmacology ( European Journal of Pharmacology )  908   174373 - 174373   2021年10月 [ 査読有り ]

    掲載種別: 研究論文(学術雑誌)

     概要を見る

    Patients with adult T-cell leukemia (ATL), caused by the human T-cell leukemia virus type 1 (HTLV-1), exhibit poor prognosis owing to drug resistance. Pimozide is a dopamine D2 receptor antagonist and antipsychotic shown to exhibit anticancer activity. Herein, we investigated whether pimozide exerts anti-ATL effects and explored the mechanisms underlying these effects. Pimozide inhibited cell growth and survival in HTLV-1-infected T cells but not in the uninfected T cells. The dopamine D2 receptor subfamily mRNA expression levels in HTLV-1-infected T cells were high. Pimozide induced G1 cell cycle arrest concomitant with the upregulation of p21/p27/p53, and suppression of cyclin D2/E, cyclin-dependent kinase 2/4/6 and c-Myc expression, and pRb phosphorylation. Pimozide also induced apoptosis by activating caspases, upregulating pro-apoptotic proteins and downregulating anti-apoptotic proteins. Additionally, it promoted reactive oxygen species (ROS) generation and increased the expression of the endoplasmic reticulum stress marker activating transcription factor 4 and the DNA damage-inducible protein GADD45α and the phosphorylation of the DNA damage marker H2AX. Furthermore, pimozide-induced cytotoxicity was partially inhibited by a ROS scavenger, and pan-caspase and necroptosis inhibitors, indicating the involvement of caspase-dependent and -independent lethal pathways. The activities of the nuclear factor-κB, Akt, STAT3/5 and AP-1 signaling pathways were inhibited via the dephosphorylation of IκBα, IκB kinase α/β, Akt and STAT3/5, in addition to reduced JunB and JunD expression in HTLV-1-infected T cells. Pimozide also exhibited potent anti-ATL activity in the xenograft mouse model. These findings demonstrated the efficacy of pimozide as a potential therapeutic agent for ATL.

  • Importin β1 regulates cell growth and survival during adult T cell leukemia/lymphoma therapy.

    Ishikawa C, Senba M, Mori N

    Investigational new drugs ( Investigational New Drugs )  39 ( 2 ) 317 - 329   2020年09月 [ 査読有り ]

    掲載種別: 研究論文(学術雑誌)

     概要を見る

    There is no cure for adult T cell leukemia/lymphoma (ATLL) associated with human T cell leukemia virus type 1 (HTLV-1), and novel targeted strategies are needed. NF-κB and AP-1 are crucial for ATLL, and both are transported to the nucleus by an importin (IPO)α/β heterodimeric complex to activate target genes. In this study, we aimed to elucidate the function of IPOβ1 in ATLL. The expression of IPOβ1 was analyzed by western blotting and RT-PCR. Cell growth, viability, cell cycle, apoptosis and intracellular signaling cascades were examined by the water-soluble tetrazolium-8 assay, flow cytometry and western blotting. Xenograft tumors in severe combined immune deficient mice were used to evaluate the growth of ATLL cells in vivo. IPOβ1 was upregulated in HTLV-1-infected T cell lines. Further, IPOβ1 knockdown or the IPOβ1 inhibitor importazole and the IPOα/β1 inhibitor ivermectin reduced HTLV-1-infected T cell proliferation. However, the effect of inhibitors on uninfected T cells was less pronounced. Further, in HTLV-1-infected T cell lines, inhibitors suppressed NF-κB and AP-1 nuclear transport and DNA binding, induced apoptosis and poly (ADP-ribose) polymerase cleavage, and activated caspase-3, caspase-8 and caspase-9. Inhibitors also mediated G1 cell cycle arrest. Moreover, the expression of NF-κB- and AP-1-target proteins involved in cell cycle and apoptosis was reduced. In vivo, the IPOα/β1 inhibitor ivermectin decreased ATLL tumor burden without side effects. IPOβ1 mediated NF-κB and AP-1 translocation into ATLL cell nuclei, thereby regulating cell growth and survival, which provides new insights for targeted ATLL therapies. Thus, ivermectin, an anti-strongyloidiasis medication, could be a potent anti-ATLL agent.

  • The anti-malaria agent artesunate exhibits cytotoxic effects in primary effusion lymphoma.

    Ishikawa C, Mori N

    Investigational new drugs ( Investigational New Drugs )    2020年09月 [ 査読有り ]

    掲載種別: 研究論文(学術雑誌)

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著書 【 表示 / 非表示

  • Mechanisms of cancer formation under interplay between host immunity and human papillomavirus (HPV) infection

    Senba M, Mori N ( 担当: 共著 )

    Nova Science Publishers  2016年

  • Challenge to the threat of invisible transmission: global health security for the control of emerging infectious diseases outbreaks

    Senba M, Mori N ( 担当: 共著 )

    Nova Science Publishers  2016年

  • Mechanisms of cancer formation under interplay between host immunity and human papillomavirus (HPV) infection

    Senba M, Mori N ( 担当: 単著 )

    Nova Science Publishers  2016年

  • Challenge to the threat of invisible transmission: global health security for the control of emerging infectious diseases outbreaks

    Mori Naoki ( 担当: 単著 )

    ■■■  2016年

  • Challenge to the threat of invisible transmission: Global health security for the control of emerging infectious diseases outbreaks

    Senba M, Mori N ( 担当: 単著 )

    Nova Science Publishers  2016年

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MISC(その他業績・査読無し論文等) 【 表示 / 非表示

  • MALT1 as a novel therapeutic target for adult T-cell leukemia

    森直樹, 石川千恵

    第81回日本血液学会学術集会プログラム・抄録集     S161   2019年10月

     

  • インポーチンβ1はKSHV感染原発性体腔液性リンパ腫の細胞増殖と生存を司る

    森直樹, 石川千恵

    第67回日本ウイルス学会学術集会     P-DN-22   2019年10月

     

  • 新規PI3K/HDAC二重阻害剤CUDC-907は原発性体腔液性リンパ腫の複数の細胞生存シグナルを抑制する

    森直樹, 石川千恵

    第78回日本癌学会学術総会プログラム集     187   2019年09月

     

  • 成人 T 細胞白血病の新規治療標的 MALT1

    森直樹, 石川千恵

    第6回日本HTLV-1学会学術集会プログラム集     80   2019年08月

     

  • Evaluation of artesunate for the treatment of adult T‐cell leukemia

    森直樹, 石川千恵

    臨床血液   59 ( 9 ) 1720 - 1720   2018年09月

     

    J-GLOBAL

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特許等知的財産 【 表示 / 非表示

  • 抗ウイルス剤

    特願 2010-082166  (2010年03月31日)

    特開 2011-213636  (2011年10月27日)

    特許 5610131  (2014年09月12日)

    森直樹, 只野昌之, 玉城和美, 仲間真司

  • 医薬およびこれに使用する抽出物

    特願 2006-287692  (2006年10月23日)

    特許 4649617  (2010年12月24日)

    森直樹, 吉見直己, 森岡孝満, 和田浩二, 岩崎公典

  • ウイルス関連悪性腫瘍剤

    特願 2006-190076  (2006年07月11日)

    特許 4337986  (2009年07月10日)

    森直樹

  • 抗ヘルペスウイルス組成物及び抗ヘルペスウイルス作用を有する発酵モモタマナ抽出物の製造方法

    特願 2005-36603  (2005年02月14日)

    森 直樹, 稲福盛雄, 稲福直, 藤野哲也, 与那覇惠

科研費獲得情報 【 表示 / 非表示

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