廣田 毅（ヒロタ　ツヨシ）

廣田 毅
学位
理学博士
所属・職位
名古屋大学トランスフォーマティブ生命分子研究所
特任准教授
URL
http://www.itbm.nagoya-u.ac.jp/ja/kay-hirota_group/
研究分野
時間生物学、ケミカルバイオロジー

原著論文

  1. Srivastava A, Hirota T, Irle S, Tama F.
    Conformational dynamics of human protein kinase CK2α and its effect on function and inhibition.
    Proteins. 2018 Mar;86(3):344-353.
  2. Hatori M, Gronfier C, Van Gelder RN, Bernstein PS, Carreras J, Panda S, Marks F, Sliney D, Hunt CE, Hirota T, Furukawa T, Tsubota K.
    Global rise of potential health hazards caused by blue light-induced circadian disruption in modern aging societies.
    NPJ Aging Mech Dis. 2017 Jun 16;3:9.
  3. Zhao X, Hirota T, Han X, Cho H, Chong LW, Lamia K, Liu S, Atkins AR, Banayo E, Liddle C, Yu RT, Yates JR 3rd, Kay SA, Downes M, Evans RM.
    Circadian Amplitude Regulation via FBXW7-Targeted REV-ERBα Degradation.
    Cell. 2016 Jun 16;165(7):1644-1657.
  4. Lee JW, Hirota T, Kumar A, Kim NJ, Irle S, Kay SA. Development of Small-Molecule Cryptochrome Stabilizer Derivatives as Modulators of the Circadian Clock. ChemMedChem. 2015 Sep;10(9):1489-97. doi: 10.1002/cmdc.201500260. Epub 2015 Jul 14
  5. Oshima T, Yamanaka I, Kumar A, Yamaguchi J, Nishiwaki-Ohkawa T, Muto K, Kawamura R, Hirota T, Yagita K, Irle S, Kay SA, Yoshimura T, Itami K.:C-H activation generates period-shortening molecules that target cryptochrome in the mammalian circadian clock. Angew Chem Int Ed Engl. 2015 Jun 8;54(24):7193-7. doi: 10.1002/anie.201502942. Epub 2015 May 8
  6. T. Hirota and S.A. Kay. Identification of small-molecule modulators of the circadian clock.. Methods Enzymol. 551, 267-282 (2015)
  7. St. John, P.C., Hirota, T., Kay, S.A., and Doyle, F.J. 3rd: Spatiotemporal separation of PER and CRY posttranslational regulation in the mammalian circadian clock. Proc. Natl. Acad. Sci. USA, 111: 2040-2045 (2014)
  8. Weger, M., Weger, B.D., Diotel, N., Rastegar, S., Hirota, T., Kay, S.A., Strahle, U., and Dickmeis, T.: Real-time in vivo monitoring of circadian E-box enhancer activity: a robust and sensitive zebrafish reporter line for developmental, chemical and neural biology of the circadian clock. Dev. Biol., 380: 259-273 (2013)
  9. Hirota, T., Lee, J.W., St. John, P.C., Sawa, M., Iwaisako, K., Noguchi, T., Pongsawakul, P.Y., Sonntag, T., Welsh, D.K., Brenner, D.A., Doyle, F.J. 3rd, Schultz, P.G., and Kay, S.A.: Identification of small molecule activators of cryptochrome. Science, 337: 1094-1097 (2012)
  10. Lee, J.W.*, Hirota, T.* (*; equal contribution), Peters, E.C., Garcia, M., Gonzalez, R., Cho, C.Y., Wu, X., Schultz, P.G., and Kay, S.A.: A small molecule modulates circadian rhythms through phosphorylation of the period protein. Angew. Chem. Int. Ed., 50: 10608-10611 (2011)
  11. Hatori, M.*, Hirota, T.* (*; equal contribution), Iitsuka, M., Kurabayashi, N., Haraguchi, S., Kokame, K., Sato, R., Nakai, A., Miyata, T., Tsutsui, K., and Fukada, Y.: Light-dependent and circadian clock-regulated activation of sterol regulatory element-binding protein, X-box-binding protein 1, and heat shock factor pathways. Proc. Natl. Acad. Sci. USA, 108: 4864-4869 (2011)
  12. Hirota, T., Lee, J.W., Lewis, W.G., Zhang, E.E., Breton, G., Liu, X., Garcia, M., Peters, E.C., Etchegaray, J.P., Traver, D., Schultz, P.G., and Kay, S.A.: High-throughput chemical screen identifies a novel potent modulator of cellular circadian rhythms and reveals CKIα as a clock regulatory kinase. PLoS Biol., 8: e1000559 (2010)
  13. Zhang, E.E.*, Liu, Y.*, Dentin, R., Pongsawakul, P.Y., Liu, A.C., Hirota, T., Nusinow, D.A., Sun, X., Landais, S., Kodama, Y., Brenner, D.A., Montminy, M., and Kay, S.A.: Cryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis. Nat. Med., 16: 1152-1156 (2010)
  14. Kurabayashi, N., Hirota, T., Sakai, M., Sanada, K., and Fukada, Y.: DYRK1A and GSK-3 : A dual kinase mechanism directing proteasomal degradation of CRY2 for circadian timekeeping. Mol. Cell Biol., 30: 1757-1768 (2010)
  15. Hirota, T., Kon, N., Itagaki, T., Hoshina, N., Okano, T., and Fukada, Y.: Transcriptional repressor TIEG1 regulates Bmal1 gene through GC box and controls circadian clockwork. Genes Cells, 15: 111-121 (2010)
  16. Zhang, E.E.*, Liu, A.C.*, Hirota, T.* (* equal contribution), Miraglia, L.J., Welch, G., Pongsawakul, P.Y., Liu, X., Atwood, A., Huss, J.W. 3rd, Janes, J., Su, A.I., Hogenesch, J.B., and Kay, S.A.: A genome-wide RNAi screen for modifiers of the circadian clock in human cells. Cell, 139: 199-210 (2009)
  17. Hirota, T., Lewis, W.G., Liu, A.C., Lee, J.W., Schultz, P.G., and Kay, S.A.: A chemical biology approach reveals period shortening of the mammalian circadian clock by specific inhibition of GSK-3b. Proc. Natl. Acad. Sci. USA, 105: 20746-20751 (2008)
  18. Kon, N., Hirota, T., Kawamoto, T., Kato, Y. and Fukada, Y.: Activation of TGF-b/activin signaling resets circadian clock through rapid induction of Dec1 transcripts. Nat. Cell Biol., 10: 1463-1469 (2008)
  19. Tsuji, T., Hirota, T., Takemori, N., Komori, N., Yoshitane, H., Fukuda, M., Matsumoto, H., and Fukada, Y.: Circadian Proteomics of the Mouse Retina. Proteomics, 7: 3500-3508 (2007)
  20. Kurabayashi, N., Hirota, T., Harada, Y., Sakai, M. and Fukada, Y.: Phosphorylation of mCRY2 at Ser557 in the hypothalamic suprachiasmatic nucleus of the mouse. Chronobiol. Int., 23: 129-134 (2006)
  21. Harada, Y., Sakai, M., Kurabayashi, N., Hirota, T. and Fukada, Y.: Ser-557-phosphorylated mCRY2 is degraded upon synergistic phosphorylation by glycogen synthase kinase-3b. J. Biol. Chem., 280: 31714-31721 (2005)
  22. Hayashi, Y.*, Sanada, K.*, Hirota, T., Shimizu, F. and Fukada, Y.: p38 Mitogen-activated protein kinase regulates oscillation of chick pineal circadian clock. J. Biol. Chem., 278: 25166-25171 (2003)
  23. Hirota, T., Okano, T., Kokame, K., Shirotani-Ikejima, H., Miyata, T. and Fukada, Y.: Glucose down-regulates Per1 and Per2 mRNA levels and induces circadian gene expression in cultured rat-1 fibroblasts. J. Biol. Chem., 277: 44244-44251 (2002)
  24. Okano, T., Yamamoto, K., Okano, K., Hirota, T., Kasahara, T., Sasaki, M., Takanaka, Y. and Fukada, Y.: Chicken pineal clock genes: Implication of BMAL2 as a bidirectional regulator in the circadian clock oscillation. Genes Cells, 6: 825-836 (2001)
  25. Hirota, T., Kagiwada, S., Kasahara, T., Okano, T., Murata, M. and Fukada, Y.: Effect of brefeldin A on melatonin secretion of chick pineal cells. J. Biochem., 129: 51-59 (2001)
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総説等

  1. Hirota, T. and Kay, S.A.: Chemical screens for clock modulators. Methods Enzymol., (in press)
  2. Tsutsui, K., Haraguchi, S., Hatori, M., Hirota, T. and Fukada, Y.: Biosynthesis and biological actions of pineal neurosteroids in domestic birds. Neuroendocrinology, 98: 97-105 (2013)
  3. Tsutsui, K., Haraguchi, S., Inoue, K., Miyabara, H., Ubuka, T., Hatori, M., Hirota, T. and Fukada, Y.: New biosynthesis and biological actions of avian neurosteroids. J. Exp. Neurosci., 7: 15-29 (2013)
  4. Hirota, T. and Kay, S.A.: High-throughput screening and chemical biology: new approaches for understanding circadian clock mechanisms. Chem. Biol., 16: 921-927 (2009)
  5. Hirota, T. and Fukada, Y.: Resetting mechanism of central and peripheral circadian clocks in mammals. Zool. Sci., 21: 359-368 (2004)
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