Isao NAGURO

名黒 功 なぐろ いさお
略歴
平成 8年 3月 鳥取県立米子東高等学校 卒業
  平成12年 3月 東京大学 薬学部 卒業
  平成14年 3月 東京大学 大学院薬学系研究科 修士課程 修了
  平成17年 3月 東京大学 大学院薬学系研究科 博士課程 修了
  平成17年 4月 東京大学 大学院薬学系研究科 寄付講座教員
  平成18年 4月 東京大学 大学院薬学系研究科 助手
  平成19年 4月 東京大学 大学院薬学系研究科 助教
  平成25年 3月 東京大学 大学院薬学系研究科 講師
  平成28年12月 東京大学 大学院薬学系研究科 准教授
 免許・資格  
  平成12年 薬剤師免許取得
  平成24年 第1種放射線取扱主任者免許取得
CURRICULUM VITAE
Name:
 Isao Naguro
Date and place of birth: 6 March, 1978, Tottori Japan
Nationality: Japanese
Affiliation:  
  Position and title: Lecturer of The University of Tokyo
  Dept./ Laboratory: Laboratory of Cell Signaling ,Graduate School of Pharmaceutical Sciences
  Institution: The University of Tokyo
  Address: 7-3-1 Hongo, Bunkyo-ku, Tokyo
  Phone: +81-3-5841-4859
  Fax: +81-3-5841-4798
  E-mail: nagurois (at) mol.f.u-tokyo.ac.jp

Degrees:  
 
2005
Ph.D. in Pharmaceutical Science The University of Tokyo, Japan
 
2002
Masters in Pharmaceutical Science The University of Tokyo, Japan
 
2000
Bachelor of Science The University of Tokyo, Japan
Awards and Honors:  
 
2016
apanese Biochemical Society Young Investigator Award 2016
 
2009
Young Investigator Award in 4th Cell Stress Society International Meeting
Education and Academic Background:
  2016-present Associate Professor, Laboratory of Cell Signaling, The University of Tokyo, Japan
Subjects of Research:
  1. Cellular signal transduction in response to physicochemical stress (mainly osmotic stress).
  2. Establishment and performing of genome-wide siRNA screening using mammalian cells with high-content image analyzer
  3. Stress signaling in tumorigenesis and metastasis of cancer, focusing on apoptosis signal-regulating kinase (ASK) family
  2018 Mar-Oct Visiting Scholar in UC Berkeley, Department of Bioengineering, U.S.A
Purpose: Applying single cell western technology to cellular stress response. PI: Prof. Amy E. Herr
  2013-2016 Lecturer, Laboratory of Cell Signaling, The University of Tokyo, Japan
  2014 Jul   Cold Spring Harbor Laboratory course program (Single Cell Analysis)
  2010 Jul-Sep The visiting researcher of National University of Singapore, Department of Biological Sciences, Singapore
Purpose: Investigating the involvement of ASK3 in mechanical stress
Mentor: Dr. Sawada
  2005-2013 Assistant Professor, Laboratory of Cell Signaling, The University of Tokyo, Japan
  2010 Jul-Sep Visiting researcher in National University of Singapore, Department of Biological Sciences, Singapore
Purpose: Investigating the involvement of ASK3 in mechanical stress   
PI: Dr. Yasuhiro Sawada
  2002-2005 Ph.D. course in Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan
    Thesis Title: “The regulation of Ca2+ signaling through voltage-dependent L-type Ca2+ cannel CaV1.2 and the interacting proteins”
  2000-2002 Master course in Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan
  2000 BSc in Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan
Professional Societies:
  · The Molecular Biology Society of Japan
· The Japanese Biochemical Society
· The Japanese Pharmacological Society
· Japan Society for Cell Biology
· Japanese Cancer Association
· The Japanese Association for Molecular Target Therapy of Cancer
Publications:
  1. Tsuburaya, N., Homma, K., Higuchi, T., Balia, A., Yamakoshi, H., Shibata, N., Nakamura, S., Nakagawa, H., Ikeda, S. I., Umezawa, N., Kato, N., Yokoshima, S., Shibuya, M., Shimonishi, M., Kojima, H., Okabe, T., Nagano, T., Naguro, I., Imamura, K., Inoue, H., Fujisawa, T. and Ichijo, H.
    A small-molecule inhibitor of SOD1-Derlin-1 interaction ameliorates pathology in an ALS mouse model.
    Nat. Commun., 9, 2668 (2018). doi: 10.1038/s41467-018-05127-2.
  2. Cheng, R., Takeda, K., Naguro, I., Hatta, T., Iemura, S., Natsume, T., Ichijo, H. and Hattori, K.
    b-TrCP-dependent degradation of ASK1 suppresses the induction of the apoptotic response by oxidative stress.
    Biochim. Biophys. Acta – Gen. Subj., 1862, 2271-2280 (2018). doi: 10.1016/j.bbagen.2018.07.015.
  3. Imamura, K., Yoshitane, H., Hattori, K., Yamaguchi, M., Yoshida, K., Okubo, T., Naguro, I., Ichijo, H. and Fukada, Y.
    ASK family kinases mediate cellular stress and redox signaling to circadian clock.
    Proc. Natl. Acad. Sci. USA., 115, 3646-3651 (2018). doi: 10.1073/pnas.1719298115.
  4. Watanabe, K., Umeda, T., Niwa, K., Naguro, I. and Ichijo, H.
    A PP6-ASK3 module coordinates the bidirectional cell volume regulation under osmotic stress.
    Cell Rep., 22, 2809-2817 (2018). doi: 10.1016/j.celrep..2018.02.045.
  5. Kamiyama, M., Naguro, I. and Ichijo, H.
    mASKing cancer cells in a tumor microenvironment.
    Cell Cycle, (commentary), 17, 139-140 (2018). doi: 10.1080/15384101.2017.1407402.
  6. Hirata, Y., Katagiri, K., Nagaoka, K., Morishita, T., Kudoh, Y., Hatta, T., Naguro, I., Kano, K., Udagawa, T., Natsume, T., Aoki, J., Inada, T., Noguchi, T., Ichijo, H. and Matsuzawa, A.
    TRIM48 promotes ASK1 activation and cell death through ubiquitination-dependent degradation of the ASK1-negative regulator PRMT1.
    Cell Rep., 21, 2447-2457 (2017). doi: 10.1016/j.celrep.2017.11.007.
  7. Hattori, K., Ishikawa, H., Sakauchi, C., Takayanagi, S.,> Naguro, I. and Ichijo, H.
    Cold stress-induced ferroptosis involves the ASK1-p38 pathway.
    EMBO Rep., 18, 2067-2078 (2017). doi: 10.15252/embr.201744228.
  8. Kamiyama, M., Shirai, T., Tamura, S., Suzuki-Inoue, K., Ehata, S., Takahashi, K., Miyazono, K., Hayakawa, Y., Sato, T., Takeda, K., Naguro, I. and Ichijo, H.
    ASK1 facilitates tumor metastasis through phosphorylation of an ADP receptor P2Y12 in platelets.
    Cell Death Differ., 24, 2066-2076 (2017). doi: 10.1038/cdd.2017.114.
  9. Maruoka, S., Gon, Y., Mizumura, K., Okamoto, S., Tsuya, K., Shikano, S., Soda, K., Naguro, I., Ichijo, H. and Hashimoto, S.
    Involvement of apoptosis signal-regulating kinase-1 in house dust mite-induced allergic asthma in mice.
    Allergol. Int., 66S, S50-S52 (2017). doi: 10.1016/j.alit.2017.05.007.
  10. Ryuno, H., Naguro, I. and Kamiyama, M.
    ASK family and cancer.
    Adv. Biol. Regul., 66, 72-84 (2017). doi: 10.1016/j.jbior.2017.05.003.
  11. Naguro, I.
    Analysis of ASK3 that regulates bidirectional osmotic stress response.
    Seikagaku, 89, 230-240 (2017) (Japanese). doi: 10.14952/SEIKAGAKU.2017.890230.
  12. Yamaguchi, N., Sekine, S., Naguro, I., Sekine, Y. and Ichijo, H.
    KLHDC10 deficiency protects mice against TNFa-induced systemic inflammation.
    PLOS one, 11, e0163118 (2016). doi: 10.1371/journal.pone.0163118.
  13. Koizumi, S., Irie, T., Hirayama, S., Sakurai, Y., Yashiroda, H., Naguro, I., Ichijo, H., Hamazaki, J. and Murata, S.
    The aspartyl protease DDI2 activates Nrf1 to compensate for proteasome dysfunction.
    eLIFE, 5, e18357 (2016).doi: 10.7554/eLife.18357.
  14. Zhou, X., Naguro, I., Ichijo, H. and Watanabe, K.
    Mitogen-activated protein kinases as key players in osmotic stress signaling.
    Biochem. Biophys. Acta, (review article),1860, 2037-2052 (2016). doi: 10.1016/j.bbagen.2016.05.032.
  15. Sekine, S., Yao, A., Hattori, K., Sugawara, S., Naguro, I., Koike, M., Uchiyama, Y., Takeda, K. and Ichijo, H.
    The ablation of mitochondrial protein phosphatase Pgam5 confers resistance against metabolic stress.
    EBioMedicine, 5, 82-92 (2016). doi: 10.1016/j.ebiom.2016.01.031.
  16. Hattori, K., Naguro, I., Okabe, K., Funatsu, T., Furutani, S., Takeda, K. and Ichijo, H.
    ASK1 signaling regulates brown and beige adipocyte function.
    Nat. Commun., 7: 11158 (2016).
  17. Maruyama, J., Kobayashi, Y., Umeda, T., Vandewalle, A., Takeda, K., Ichijo, H. and Naguro, I.
    Osmotic stress induces the phosphorylation of WNK4 Ser575 via the p38MAPK-MK pathway.
    Sci. Rep.
    , 6, 18710 (2016).
  18. Fujisawa, T., Takahashi, M., Tsukamoto, Y., Yamaguchi, N., Nakoji, M., Endo, M., Kodaira, H., Hayashi, Y., Nishitoh, H., Naguro, I., Homma, K. and Ichijo, H.
    The ASK1-specific inhibitors K811 and K812 prolong survival in a mouse model of amyotrophic lateral sclerosis.
    Hum. Mol. Genet., 25, 245-253 (2016).
  19. Fujisawa, T., Yamaguchi, N., Kadowaki, H., Tsukamoto, Y., Tsuburaya, N., Tsubota, A., Takahashi, H., Naguro, I., Takahashi, Y., Goto, J., Tsuji, S., Nishitoh, H., Homma, K. and Ichijo, H. A systematic immunoprecipitation approach reinforces the concept of common conformational alterations in amyotrophic lateral sclerosis-linked SOD1 mutants.
    Neurobiol. Dis., 82, 478-486 (2015).
  20. Kamiyama, M., Naguro, I., Ichijo, H.
    In vivo gene manipulation reveals the impact of stress-responsive MAPK pathways on tumor progression.
    Cancer Sci., (review article), 106, 785-796 (2015).
  21. Watanabe, T., Sekine, S., Naguro, I., Sekine, Y. and Ichijo, H.
    Apoptosis Signal-regulating Kinase 1(ASK1)-p38 pathway-dependent cytoplasmic translocation of the orphan nuclear receptor NR4A2 is required for oxidative stress-induced necrosis.
    J. Biol. Chem., 290, 10791-10803 (2015).
  22. Mosallanejad, K., Sekine, Y., Ishikura-Kinoshita, S., Kumagai, K., Nagano, T., Matsuzawa, A., Takeda, K., Naguro, I. and Ichijo, H.
    The DEAH-Box RNA Helicase DHX15 activates NF-κB and MAPK signaling downstream of MAVS during antiviral responses.
    Sci. Signal., 7, ra40 (2014).
  23. Maruyama, T., Araki, T., Kawarazaki, Y., Naguro, I., Heynen, S., Aza-Blanc, P., Ronai, Z., Matsuzawa, A. and Ichijo, H. 
    Roquin-2 promotes ubiquitin-mediated degradation of ASK1 to regulate stress responses.
    Sci. Signal., 7, ra8 (2014)
  24. Kawarazaki, Y., Ichijo, H. and Naguro, I.
    Apoptosis Signal-Regulating Kinase 1 (ASK1) as a therapeutic target.
    Expert Opin. Ther, Tar. (review article), 18, 651-664 (2014).
  25. Homma, K., Fujisawa, T., Tsuburaya, N., Yamaguchi, N., Kadowaki, H., Takeda, K., Nishitoh, H.,  Matsuzawa, A., Naguro, I., and Ichijo, H.
    SOD1 as a molecular switch for initiating the homeostatic ER stress response under zinc deficiency.
    Mol. Cell, 52, 75-86 (2013).
  26. Shiizaki, S., Naguro, I. and Ichijo, H.
    Activation mechanisms of ASK1 in response to various stresses and its significance in intracellular signaling.
    Adv. Biol. Regul., (review article), 53, 135-144 (2013).
  27. Naguro, I., Umeda, T., Kobayashi, Y., Maruyama, J., Hattori, K., Shimizu, Y., Kataoka, K., Kim-Mitsuyama, S., Uchida, S., Vandewalle, A., Noguchi, T., Nishitoh, H., Matsuzawa, A., Takeda, K. and Ichijo, H.
    ASK3 responds to osmotic stress and regulates blood pressure by suppressing WNK1-SPAK/OSR1 signaling in the kidney.
    Nat. Commun., 3, 1285 (2012).
  28. Fujisawa, T., Homma, K., Yamaguchi, N., Kadowaki, H., Tsuburaya, N., Naguro, I., Matsuzawa, A., Takeda, K., Takahashi, Y., Goto, J., Tsuji, S., Nishitoh, H. and Ichijo, H.
    A novel monoclonal antibody reveals a conformational alteration shared by amyotrophic lateral sclerosis-linked SOD1 mutants.
    Ann. Neurol., 72, 739-749 (2012).
  29. Sekine,Y., Takagahara,S., Hatanaka, R., Watanabe, T., Oguchi, H., Noguchi, T., Naguro, I., Kobayashi, K., Tsunoda, M., Funatsu, T., Nomura, H., Toyoda, T., Matsuki, N., Kuranaga, E., Miura, M., Takeda, K. and Ichijo,H.
    p38 MAP kinase regulates the expression of genes in the dopamine synthesis pathway through phosphorylation of NR4A nuclear receptors.
    J. Cell Sci. 124, 3006-3016 (2011).
  30. Takeda, K., Naguro, I., Nishitoh, H.,Matsuzawa, A. and Ichijo, H.
    Apoptosis signaling kinases: from stress response to health outcomes.
    Antioxid. Redox Signal. (review article), 15, 719-761 (2011).
  31. Maruyama, T., Kadowaki, H., Okamoto, N., Nagai, A., Naguro, I., Matsuzawa, A., Shibuya, H., Tanaka, K., Murata, S., Takeda, K., Nishitoh, H. and Ichijo, H.
    CHIP-dependent termination of MEKK2 regulates temporal ERK activation required for proper hyperosmotic response.
    EMBO J., 29, 2501-2514 (2010).
  32. Shimizu, Y., Naguro, I., Nishitoh, H. and Ichijo, H.
    ER stress-induced cell death and inflammatory signaling: a therapeutic insight into intractable diseases.
    Endoplasmic Reticulum Stress and Human Disease, (review article), in press.
  33. Hattori, K., Naguro, I., Runchel, C. and Ichijo, H.
    The roles of ASK family proteins in stress responses and diseases.
    Cell Communication and Signaling, (review article), 7, 9 (2009).
  34. Maruyama, J., Naguro, I., Takeda, K. and Ichijo, H.
    Stress-Activated MAP Kinase Cascades in Cellular Senescence.
    Curr. Med. Chem., (review article), 16, 1229-1235 (2009).
  35. Iriyama, T., Takeda, K., Nakamura, H., Morimoto, Y., Kuroiwa, T., Mizukami, J., Umeda, T., Noguchi, T., Naguro, I., Nishitoh, H., Saegusa, K., Tobiume, K., Homma, T., Shimada, Y., Tsuda, H., Aiko, S., Imoto, I., Inazawa, J., Chida, K., Kamei, Y., Kozuma, S., Taketani, Y., Matsuzawa, A. and Ichijo, H.
    ASK1 and ASK2 differentially regulate the counteracting roles of apoptosis and inflammation in tumorigenesis.
    EMBO J., 28, 843-853 (2009).
  36. Noguchi, T., Ishii, K., Fukutomi, H., Naguro, I., Matsuzawa, A., Takeda, K. and Ichijo, H.
    Requirement of reactive oxygen species-dependent activation of ASK1-p38 MAP kinase pathway for extracelluler ATP-induced apoptosis in macrophage.
    J. Biol. Chem., 283, 7657-7665 (2008).
  37. Takeda, K., Noguchi, T., Naguro, I. and Ichijo, H.
    Apoptosis Signal-regulating Kinase 1 (ASK1) in stress and immune response.
    Annu. Rev. Pharmacol. Toxicol., (review article), 48, 199-225 (2008).
  38. Takeda, K., Shimozono, R., Noguchi, T., Umeda, T., Morimoto, Y., Naguro, I., Tobiume, K., Saitoh, M., Matsuzawa, A. and Ichijo, H.
    Apoptosis signal-regulating kinase 2 (ASK2) functions as a MAP3K in a heteromeric complex with ASK1.
    J. Biol. Chem., 282, 7522-7531 (2007).
  39. Yokoyama, U., Minamisawa, S., Adachi-Akahane, S., Akaike, T., Naguro, I., Funakoshi, K., Iwamoto, M., Nakagome, M., Uemura, N., Hori, H., Yokota, S. and Ishikawa, Y. Multiple transcripts of Ca2+ channel alpha1-subunit and a novel spliced variant of the alpha1C-subunit in rat ductus arteriosus.
    Am. J. Physiol. Heart Circ. Physiol., 290, H1660-1670 (2006).
  40. Naguro, I., Adachi-Akahane, S. and Ichijo, H.
    Calcium signaling via voltage-dependent L-type Ca2+ channels.
    Signal Transduction (review article), 4, 195-205 (2004).
  41. Naguro, I., Nagao, T. and Adachi-Akahane, S. Ser(1901) of alpha(1C) subunit is required for the PKA-mediated enhancement of L-type Ca(2+) channel currents but not for the negative shift of activation.
    FEBS Lett., 489, 87-91 (2001).

    論文業績(邦文)

  1. 名黒 功: 両方向性の浸透圧ストレス応答を統御するASK3の研究、生化学,89(2), 230-240, 2017.

  2. 名黒功:哺乳類細胞におけるシグナリングを対象としたゲノムワイドsiRNAスクリーニング,実験医学増刊「知る・見る・活かす!シグナリング研究2015」一條秀憲、南泰宏 編,羊土社,33(10), 1667-1673, 2015.

  3. 渡邊謙吾、名黒 功、一條秀憲:ハイコンテントゲノムワイドsiRNAスクリーニングによるシグナル伝達研究への応用、実験医学,32(9),1405-1410,2014.

  4. 河原崎陽介、名黒功、一條秀憲:酸化ストレス応答キナーゼASK1の機能と疾患へのかかわり,医学のあゆみ,247(9),746-752,2013.

  5. 河野泰秀、名黒功、一條秀憲:癌とシグナル-ストレス応答シグナル(JNK経路)と癌,遺伝子医学MOOK6-シグナル伝達病を知る-,菅村和夫他 編,メディカルドゥ,192-197,2006.

  6. 名黒 功、松沢 厚、藤野悟央、一條秀憲:ASK1シグナリングのRedoxによる制御と自然免疫応答への関与,Annual Review免疫2007,奥村康他編、中外医学社,73-84,2006.

    研究費獲得状況

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