京都大学化学研究所研究者情報   [ English | Japanese ]


上杉 志成 (うえすぎ もとなり )

生体機能化学研究系 ケミカルバイオロジー
(医学研究科 協力講座)
教授
博士(薬学)
URL:http://www.scl.kyoto-u.ac.jp/~uesugi/
E-mail: uesugi@scl.kyoto-u.ac.jp
Tel: 0774-38-3225
Fax: 0774-38-3226

研究・教育歴
    1995.3 京都大学大学院薬学専攻博士後期課程修了
    1995.3 京都大学博士(薬学)
    1995.4〜1996.3ハーバード大学 化学・化学生物学科 内藤財団海外留学助成博士研究員
    1996.4〜1996.6ハーバード大学 化学・化学生物学科 博士研究員
    1996.7〜1998.8ハーバード大学 化学・化学生物学科 アメリカ白血病財団フェロー
    1998.9〜2005.2 ベイラー医科大学 生化学・分子生物学科 助教授 (Assistant Professor)
    2005.2〜2009.7ベイラー医科大学 生化学・分子生物学科 准教授 (Associate Professor)
    2005.4〜現在京都大学 化学研究所 教授
    2005.10〜2009.3科学技術振興機構 さきがけ研究員 兼任
    2007.10〜現在京都大学 物質−細胞統合システム拠点 教授 (京都大学 化学研究所教授 兼務)
    2009.08〜現在ベイラー医科大学 生化学・分子生物学科 非常勤准教授 兼務
    2013.01〜2017.03京都大学 物質−細胞統合システム拠点 副拠点長・教授
    2017.04~現在京都大学 物質−細胞統合システム拠点 副拠点長・連携教授
専門分野
    ケミカルバイオロジー
主な研究テーマ
  1. 小分子化合物を起爆剤とした生物学的研究
主な論文・著書
  1. Asano, L., Watanabe, M., Ryoden, Y., Usuda, K., Yamaguchi, T., Khambu, B., Takashima, M., Sato, S., Sakai, J., Nagasawa, K., Uesugi, M., Vitamin D metabolite, 25-Hydroxyvitamin D, regulates lipid metabolism by inducing degradation of SREBP/SCAP. Cell Chem Biol. 24, 207-217 (2017)
  2. Mao, D., Ando, S., Sato, S., Qin, Y., Hirata, N., Katsuda, Y., Kawase, E., Kuo, T.F., Minami, I., Shiba, Y., Ueda, K., Nakatsuji, N., Uesugi, M., A synthetic hybrid molecule for selective removal of human pluripotent stem cells from cell mixtures. Angew. Chem. Int. Ed. 56, 1765-1770 (2017)
  3. Katsuda, Y.; Sato, S.; Asano, L.; Morimura, Y.; Furuta, T.; Sugiyama, H.; Hagihara, M.; Uesugi, M., A Small Molecule That Represses Translation of G-quadruplex-containing mRNA. J. Am. Chem. Soc., 138, 9037-9040 (2016)
  4. Takaya, J.; Mio, K.; Shiraishi, T.; Kurokawa, T.; Otsuka, S.; Mori, Y.; Uesugi, M., A Potent and Site-selective Agonist of TRPA1. J. Am. Chem. Soc., 137, 15859-15864 (2015)
  5. Parvatkar, P.; Kato, N.; Uesugi, M.; Sato, S.; Ohkanda, J. , Intracellular Generation of a Diterpene-Peptide Conjugate that Inhibits 14-3-3-Mediated Interactions. J. Am. Chem. Soc., 137, 15624-15627 (2015)
  6. Sato, S.*; Watanabe, M.; Katsuda, Y.; Murata, A.; Wang, D. O.; Uesugi M., Live-cell Imaging of Endogenous mRNAs with a Small Molecule. Angew. Chem. Int. Ed. 54, 1855-1858 (2015)
  7. Frisco-Cabanos, H.L.; Watanabe, M.; Okumura, N.; Kusamori, K.; Takemoto, N.; Takaya, J.; Sato, S.; Yamazoe, S.; Takakura, Y.; Kinoshita, S.; Nishikawa, M.; Koizumi, M.; Uesugi, M. , Synthetic Molecules That Protect Cells from Anoikis and Their Use in Cell Transplantation. Angew. Chem. Int. Ed. 53, 11208-11213 (2014)
  8. Kuo, T.F.; Mao, D.; Hirata, N.; Khambu, B.; Kimura, Y.; Kawase, E.; Shimogawa, H.; Ojika, M.; Nakatsuji, N.; Ueda, K.; Uesugi, M., Selective Elimination of Human Pluripotent Stem Cells by a Marine Natural Product Derivative. J. Am. Chem. Soc. 136(28), 9798-9801 (2014)
  9. Hirata, N., Nakagawa, M., Fujibayashi, Y., Yamauchi, K., Murata, A., Minami, I., Tomioka, M., Kondo, T., Kuo, T.F., Endo, H., Inoue, H., Sato, S., Ando, S., Kawazoe, Y., Aiba, K., Nagata, K., Kawase, E., Chang, Y.T., Suemori, H., Eto, K., Nakauchi, H., Yamanaka, S., Nakatsuji, N., Ueda, K., Uesugi, M., A Chemical Probe that Labels Human Pluripotent Stem Cells Cell Reports 6(6), 1165-1174 (2014)
  10. Sakano, D.; Shiraki, N.; Kikawa, K.; Yamazoe, T.; Kataoka, M.; Umeda, K.; Araki, K.; Mao, D.; Matsumoto, S.; Nakagata, N.; Andersson, O.; Stainier, D.; Endo, F.; Kume, K.; Uesugi, M.; Kume, S., VMAT2 Identified as a Regulator of Late-stage Beta Cell Differentiation. Nat. Chem. Biol. 10, 141-148 (2014)
  11. Kita, M.; Hirayama, Y.; Yoneda, K.; Yamagishi, K.; Chinen, T.; Usui, T.; Sumiya, E.; Uesugi, M.; Kigoshi, H., Inhibition of Microtubule Assembly by A Complex of Actin and Antitumor Macrolide Aplyronine A. J. Am. Chem. Soc. 135(48), 18089–18095 (2013)
  12. Takemoto, N.; Suehara, T.; Frisco, H.; Sato, S.; Sezaki, T.; Kusamori, K.; Kawazoe, Y.; Park, S.M.; Yamazoe, S.; Mizuhata, Y.; Inoue, R.; Miller, G.; Hansen, S.; Jayson, G.; Gardiner, J.; Kanaya, T.; Tokitoh, N.; Ueda, K.; Takakura, Y.; Kioka, N.; Nishikawa, M.; Uesugi, M. , Small Molecule-induced Clustering of Heparan Sulfate Promotes Cell Adhesion. J. Am. Chem. Soc. 135 (30), 11032−11039 (2013)
  13. Natsume, A.; Ito, M.; Katsushima, K.; Ohka, F.; Hatanaka, A.; Shinjo, K.; Sato, S.; Takahashi, S.; Ishikawa, Y.; Takeuchi, I.; Shimogawa, H.; Uesugi, M.; Okano, H.; Kim, SU.;Wakabayashi, T.; Issa, JP.; Sekido, Y.; Kondo, Y. , Chromatin Regulator PRC2 Is a Key Regulator of Epigenetic Plasticity in Glioblastoma. Cancer Res. 73 (14), 4559-4570 (2013)
  14. Suzuki, T.; Arai, M.A.; Nakashima, M.; Uesugi, M. , Merging Chemistry and Biology in Emerging Countries. Chem. Biol. 20(4), 461-465 (2013)
  15. Kumagai, H.; Suemori, H.; Uesugi, M.; Nakatsuji, N.; Kawase, E., Identification of Small Molecules That Promote Human Embryonic Stem Cell Self-Renewal. Biochem Biophys Res Commun. 434(4), 710-716 (2013)
  16. Jung, D.; Abu-Elheiga, L.; Ayuzawa, R.; Gu, Z.; Shirakawa, T.; Fujiki, Y.; Nakatsuji, N.; Wakil, S.J.; Uesugi, M. , Mis-localization and Inhibition of ACC1 by a Synthetic Small Molecule Biochem J. 448(3), 409-416 (2012).
  17. Minami, I.; Yamada, K.; Otsuji, T.G.; Yamamoto, T.; Shen, Y.; Otsuka, S.; Kadota, S.; Morone, N.; Barve, M.; Asai, Y.; Tenkova-Heuser, T.; Heuser, J. E.; Uesugi, M.; Aiba, K.; Nakatsuji, N., A Small Molecule That Promotes Cardiac Differentiation of Human Pluripotent Stem Cells under Defined Cytokine- and Xeno-free Conditions. Cell Reports 2(5), 1448-1460 (2012)
  18. Kamisuki, S.; Shirakawa, T.; Kugimiya, A.; Abu-Elheiga, L.; Choo, H.; Yamada, K.; Shimogawa, H.; Wakil, SJ.; Uesugi, M. , Synthesis and Evaluation of Diarylthiazole Derivatives That Inhibit Activation of Sterol Regulatory Element-Binding Proteins J. Med. Chem. 54(13), 4923-4927 (2011).
  19. Khambu, B.; Uesugi, M.; Kawazoe, Y. , Translational Repression Stabilizes Messenger RNA of Autophagy-Related Genes Genes Cells 16(8), 857-867 (2011).
  20. Murakami, G.; Inoue, H.; Tsukita, K.; Asai, Y.; Amagai, Y.; Aiba, K.; Shimogawa, H.; Uesugi, M.; Nakatsuji, N.; Takahashi, R. , Chemical Library Screening Identifies a Small Molecule that Downregulates SOD1 Transcription for Drugs to Treat Amyotrophic Lateral Sclerosis J Biomol Screen. 16(4), 405-14 (2011).
  21. Murata, A., Sato, S., Kawazoe, Y., Uesugi, M. , Small-Molecule Fluorescent Probes for Specific RNA Targets Chem. Commun. 47(16), 4712-4714 (2011).
  22. Kawazoe, Y.; Shimogawa, H.; Sato, A.; Uesugi, M., A Mitochondrial Surface-Specific Fluorescent Probe Activated by Bioconversion Angew. Chem. Int. Ed. 50(24), 5478-81 (2011).
  23. Sumiya, E., Shimogawa, H., Sasaki, H., Tsutsumi, M., Yoshita, K., Ojika, M., Suenaga, K., Uesugi, M. , Cell-Morphology Profiling of a Natural Product Library Identifies Bisebromoamide and Miuraenamide A as Actin-Filament Stabilizers ACS Chem. Biol. 6(5), 425-31 (2011).
  24. Shirakawa, T.; Kawazoe, Y.; Tsujikawa, T.; Jung, D.; Sato, S.; Uesugi, M., Deactivation of STAT6 through Serine 707 Phosphorylation by JNK J. Biol. Chem. 286(5), 4003-4010 (2011).
  25. Sato, S.; Murata, A.; Orihara, T.; Shirakawa, T.; Suenaga, K.; Kigoshi, H.; Uesugi, M., Marine Natural Product Aurilide Activates the OPA1-Mediated Apoptosis by Binding to Prohibitin Chem. Biol. 18(1), 131-139 (2011).
  26. Sato S, Murata A, Shirakawa T, Uesugi M., Biochemical Target Isolation for Novices: Affinity-Based Strategies Chem. Biol. 17(6), 616-623 (2010).
  27. Hoshino M, Tsujimoto T, Yamazoe S, Uesugi M, Terada S. , Adhesamine, a New Synthetic Molecule, Accelerates Differentiation and Prolongs Survival of Primary-Cultured Mouse Hippocampal Neurons. Biochem. J. 427(2), 297-304 (2010).
  28. Kamisuki S, Mao Q, Abu-Elheiga L, Gu Z, Kugimiya A, Kwon Y, Shinohara T, Kawazoe Y, Sato S, Asakura K, Choo H, Sakai J, Wakil SJ, Uesugi M, A Small Molecule that Blocks Fat Synthesis by Inhibiting the Activation of SREBP Chem. Biol. 16(8),882-892 (2009).
  29. Yamazoe S, Shimogawa H, Sato S, Esko JD, Uesugi M, A Dumbbell-Shaped Small Molecule that Promotes Cell Adhesion and Growth Chem. Biol. 16(7),773-782 (2009).
  30. Jung D, Shimogawa H, Kwon Y, Mao Q, Sato S, Kamisuki S, Kigoshi H, Uesugi M, Wrenchnolol Derivative Optimized for Gene Activation in Cells J. Am. Chem. Soc. 131(13),4774-4782 (2009).
  31. Sato S, Kwon Y, Kamisuki S, Srivastava N, Mao Q, Kawazoe Y, Uesugi M, Polyproline-rod Approach to Isolatiing Protein Targets of Bioactive Small Molecules:Isolation of a New Target of Indomethacin J. Am. Chem. Soc. 129(4),873-880 (2007).
  32. Henderson YC, Frederick MJ, Jayakumar A, Choi Y, Wang MT, Kang Y, Evans R, Spring PM, Uesugi M, Clayman GL, Human LBP-32/MGR is a repressor of the P450scc in human choriocarcinoma cell line JEG-3. Placenta 28(2-3),152-160 (2006).
  33. Uesugi M, Chemical Biology of Gene Expression Peptide Science 2006 , 151 (2006).
  34. Jung D, Choi Y, Uesugi M, Small Organic Molecules that Modulate Gene Transcription Drug Discov Today 11, 452-457 (2006).
  35. Choi Y, Shimogawa H, Murakami K, Ramdas L, Zhang W, Qin J, Uesugi M, Chemical Genetic Identification of the IGF-linked Pathway That is Mediated by STAT6 and MFP2 Chemistry & Biology 13, 241-249 (2006).
  36. Uesugi, M., Synthetic molecules that modulate transcription and differentiation: hints for future drug discovery Journal of Combinatorial Chemistry and High-Throughput Screening 7, 653-659 (2004).
  37. Choi, Y., Uesugi, M., Regulation of IGF2 functions by a bioactive small molecule FASEB Journal, 18, C219-C219 (2004).
  38. Uesugi, M., Synthetic molecules that modulate transcription and differentiation: hints for future drug discovery Journal of Combinatorial Chemistry and High-Throughput Screening 7, 653-659 (2004).
  39. Kwon, Y., Arndt, H., Mao, Q., Choi, Y., Kawazoe, Y., Dervan, P. B., Uesugi, M., Small molecule transcription factor mimic J. Am. Chem. Soc. 126, 15940-15941 (2004).
  40. Choi, Y., Uesugi, M., Regulation of IGF2 functions by a bioactive small molecule FASEB Journal, 18, C219-C219 (2004).
  41. Kawazoe, Y., Tanaka, H., Uesugi, M., Chemical genetic identification of histamine receptor H1 as a stimulator of insulin-induced adipogenesis Chem. Biol. 11, 907-913 (2004).
  42. Shimogawa, H., Kwon, Y., Mao, Q., Kawazoe, Y., Choi, Y., Asada, S., Kigoshi, H., Uesugi, M., A wrench-shaped synthetic molecule that modulates a transcription factor-coactivator interaction J. Am. Chem. Soc. 126, 3461-3471 (2004).
  43. Choi, Y., Kawazoe, Y., Murakami, K., Uesugi, M., Identification of bioactive molecules by adipogenesis profiling of organic compounds FASEB Journal, 17, A605-A605 (2003).
  44. Asada, S., Choi, Y., Uesugi, M., A gene-expression inhibitor that targets an alpha-helix-mediated protein interaction J. Am. Chem. Soc. 125, 4992-4993 (2003).
  45. Choi, Y., Kawazoe, Y., Murakami, K., Misawa, H., Uesugi, M., Identification of bioactive molecules by adipogenesis profiling of organic compounds J. Biol. Chem. 278, 7320-7324 (2003).
  46. Asada, S., Choi, Y., Yamada, M., Wang, S., Hung, M., Qin, J., Uesugi, M., External control of Her2 expression and cancer cell growth by targeting a Ras-linked coactivator Proc. Natl. Acad. Sci. USA 99, 12747-12752 (2002).
  47. Jabbur J. R., Tabor, A. D., Cheng, X., Wang, H., Uesugi, M., Lozano, G., Zhang, W., Phosphorylation at threonine 18 of p53 alters hydrogen bonding attenuating mdm2 binding and TAFII31 recruitment Oncogene 21, 7100-7113 (2002).
  48. Skowyra, D., Zeremski, M., Neznanov, N., Li, M., Choi, Y., Uesugi, M., Hauser, C. A., Gu, W., Gudkov, A. V., Qin, J., Differential association of products of alternative transcripts of the candidate tumor suppressor ING1 with the mSin3/HDAC1 transcriptional corepressor complex J. Biol. Chem. 276, 8713-8719 (2001).
  49. Choi, Y., Asada, S., Uesugi, M.,, Divergent hTAF(II)31-binding motifs hidden in activation domains J. Biol. Chem. 275, 15912-15916 (2000).
  50. Park, S., Uesugi, M., Verdine, G. L., A second calcineurin binding site on the NFAT regulatory domain Proc. Natl. Acad. Sci. USA 97, 7130-7135 (2000).
  51. Park S. J., Uesugi, M., Sun, L. J., Crabtree, G. R., Verdine, G. L., Existence of a second calcineurin binding site on select isoforms of NFAT FASEB Journal, 13, A1495-A1495 (1999).
  52. Uesugi, M., Verdine, G. L., The alpha-helical FXXphiphi motif in p53: TAF interaction and discrimination by MDM2 Proc. Natl. Acad. Sci. USA 96, 14801-14806 (1999).
  53. Nyanguile, O., Uesugi, M., Austin, D. J., Verdine, G. L., A non-natural transcriptional coactivator Proc. Natl. Acad. Sci. USA 94, 13402-13406 (1997).
  54. Uesugi, M., Nyanguile, O., Lu, H., Levine, A. J., Verdine, G. L., Induced alpha-helix in the VP16 activation domain upon binding to a human TAF Science 277, 1310-1313 (1997).
  55. Kusakabe, T., Uesugi, M., Sugiura, Y., Sequence preference for strand cleavage of gapped duplexes by dynemicin A: possible mechanism of sequence-dependent double-stranded breaks Biochemistry 34, 9944-9950 (1995).
  56. Totsuka, R., Aizawa, Y., Uesugi, M., Okuno, Y., Matsumoto, T., Sugiura, Y., RNA cleavage by C-1027 chromophore, an enediyne antitumor antibiotic: high selectivity to an anticodon arm Biochem. Biophys. Res. Commun. 208, 168-173 (1995).
  57. Uesugi, M., Kusakabe, T., Sugiura, Y., Hydrophobic DNA binding of esperamicin requires conformational distortion of the host DNA Biochimi. Biophys. Acta 1261, 99-106 (1995).
  58. Kushida, T., Uesugi, M., Sugiura, Y., Kigoshi, H., Tanaka, H., Hirokawa, J., Ojika, M., Yamada, K., DNA damage by ptaquiloside, a potent bracken carcinogen: detection of selective strand breaks and identification of DNA cleavage products J. Am. Chem. Soc. 116, 479-486 (1994).
  59. Uesugi, M., Kusakabe, T., Sugiura, Y., Induced-fit association between DNA and esperamicin. Importance of structural flexibility in host DNA duplex Nucleic Acids Symp Ser. 29, 89-90 (1993).
  60. Kusakabe, T., Maekawa, K., Ichikawa, A., Uesugi, M., Sugiura, Y., Conformation-selective DNA strand breaks by dynemicin: A molecular wedge into flexible regions of DNA Biochemistry 32, 11669-11675 (1993).
  61. Uesugi, M., Sugiura, Y., New insights into sequence-recognition process of esperamicin A1 and calicheamicin g1I: origin of their selectivities and "induced fit" mechanism Biochemistry 32, 4622-4627 (1993).
  62. Tokuda, M., Fujiwara, K., Gomibuchi, T., Hirama, M., Uesugi, M., Sugiura, Y., Synthesis of a hybrid molecule containing neocarzinostatin chromophore analogue and minor groove binder Tetrahedron Letters 34, 669-672 (1993).
  63. Uesugi, M., Kusakabe, T., Sugiura, Y., Induced-fit association between DNA and esperamicin. Importance of structural flexibility in host DNA duplex Nucleic Acids Symp Ser. 29, 89-90 (1993).
  64. Uesugi, M., Sugiura, Y., DNA cleaving modes in minor groove of DNA helix by esperamicin and calicheamicin antitumor antibiotics. Nucleic Acids Symp Ser. 27, 1-2 (1992).
  65. Shiraki, T., Uesugi, M., Sugiura, Y., C-1' hydrogen abstraction of deoxyribose in DNA strand scission by dynemicin A Biochem. Biophys. Res. Commun. 188, 584-589 (1992).
  66. Uesugi, M., Sugiura, Y., Product analyses in DNA strand scission by antitumor antibiotic elsamicin A Biochem. Biophys. Res. Commun. 186, 580-587 (1992).
  67. Owa, T., Haupt, A., Otsuka, M., Kobayashi, S., Tomioka, N., Itai, A., Ohno, M., Shiraki, T., Uesugi, M., Sugiura, Y., Man-designed bleomycins: significance of the binding sites as enzyme models and of stereochemistry of the linker moiety Tetrahedron 48, 1193-1208 (1992).
  68. Uesugi, M., Sugiura, Y., DNA cleaving modes in minor groove of DNA helix by esperamicin and calicheamicin antitumor antibiotics. Nucleic Acids Symp Ser. 27, 1-2 (1992).
  69. Hirama, M., Gomibuchi, T., Fujiwara, K., Sugiura, Y., Uesugi, M., Synthesis and DNA-cleaving abilities of functional neocarzinostatin chromophore analogues. Base discrimination of a simple alcohol J. Am. Chem. Soc. 113, 9851-9853 (1991).
  70. Sugiura, Y., Arakawa, T., Uesugi, M., Shiraki, T., Ohkuma, H., Konishi, M., Reductive and nucleophilic activation products of dynemicin A with methyl thioglycolate. Rational mechanism for DNA cleavage of thiol-activated dynemicin A Biochemistry 30, 2989-2992 (1991).
  71. Uesugi, M., Sekida, T., Matsuki, S., Sugiura, Y., Selective DNA cleavage by elsamicin A and switch function of its amino sugar group Biochemistry 30, 6711-6715 (1991).
  72. Uesugi, M., Sugiura, Y., Switch-function of amino sugar on elsamicin A, a DNA binding antitumor antibiotic Nucleic Acids Symp Ser. 22, 33-4 (1990).


Update: Jul 18,2017