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RIKEN Center for Biosystems Dynamics Research Laboratory for Epigenetics Drug Discovery

Team Leader: Takashi Umehara (Ph.D.)

Research Summary

Takashi  Umehara(Ph.D.)

Epigenetics is the research field that tackles information beyond genetic information, such as chemical, reversible and heritable modifications of genomic DNA and histones. We have been developing methods to reconstitute, and detect, an epigenetic nucleosome, consisting of a DNA segment and core histones, with designed chemical modifications. Through utilization of such "epi-nucleosomes" in high-throughput screening along with structure-based drug design approaches, we plan to develop molecules that regulate lineage reprogramming of a cell and/or growth of a disease-related cell for rational development of novel "epi-drugs".

Main Research Fields

  • Medicine, Dentistry & Pharmacy

Related Research Fields

  • Chemistry
  • Biology

Keywords

  • chromatin
  • drug discovery
  • epigenome
  • gene expression
  • nucleosome

Selected Publications

  • 1.Saito, S., Kikuchi, J., Koyama, D., Sato, S., Koyama, H., Osada, N., Kuroda, Y., Akahane, K., Inukai, T., Umehara, T. and Furukawa, Y.:
    "Eradication of central nervous system leukemia of T-cell origin with a brain-permeable LSD1 inhibitor"
    Clin. Cancer Res. 25 1601-1611. 2019.
  • 2.Umezawa, N., Tsuji, K., Sato, S., Kikuchi, M., Watanabe, H., Horai, Y., Yamaguchi, M., Hisamatsu, Y., Umehara, T. and Higuchi, T.:
    "Inhibition of FAD-dependent lysine-specific demethylases by chiral polyamine analogues"
    Royal Soc. Chem. Adv. 8 36895-36902. 2018.
  • 3.Tsusaka, T., Kikuchi, M., Shimazu, T., Suzuki, T., Sohtome, Y., Akakabe, M., Sodeoka, M., Dohmae, N., Umehara, T. and Shinkai, Y.:
    "Tri-methylation of ATF7IP by G9a/GLP recruits the chromodomain protein MPP8"
    Epigenetics Chromatin. 11 56. 2018.
  • 4.Handoko, L., Kaczkowski, B., Hon, C.C., Lizio, M., Wakamori, M., Matsuda, T., Ito, T., Jeyamohan, P., Sato, Y., Sakamoto, K., Yokoyama, S., Kimura, H., Minoda, A. and Umehara, T.:
    "JQ1 affects BRD2-dependent and independent transcription regulation without disrupting H4-hyperacetylated chromatin states"
    Epigenetics. 13 410-431. 2018.
  • 5.Niwa, H., Sato, S., Hashimoto, T., Matsuno, K., Umehara, T.:
    "Crystal structure of LSD1 in complex with 4-[5-(piperidin-4-ylmethoxy)-2-(p-tolyl)pyridin-3-yl]benzonitrile"
    Molecules. 23 1538. 2018.
  • 6.Hirano, T., Fujiwara, T., Niwa, H., Hirano, M., Ohira, K., Okazaki, Y., Sato, S., Umehara, T., Maemoto, Y., Ito, A., Yoshida, M. and Kagechika, H.:
    "Development of novel inhibitors for histone methyltransferase SET7/9 based on cyproheptadine"
    ChemMedChem. 13 1530-1540. 2018.
  • 7.Yoneyama, Y., Lanzerstorfer, P., Niwa, H., Umehara, T., Shibano, T., Yokoyama, S., Chida, K., Weghuber, J., Hakuno, F. and Takahashi, S.-I.:
    "IRS-1 acts as an endocytic regulator of IGF-I receptor to facilitate sustained IGF signaling"
    eLife. 7 e32893. 2018.
  • 8.Osada, N., Kikuchi, J., Umehara, T., Sato, S., Urabe, M., Abe, T., Hayashi, N., Sugitani, M., Hanazono, Y. and Furukawa, Y.:
    "Lysine-specific demethylase 1 inhibitors prevent teratoma development from human induced pluripotent stem cells"
    Oncotarget. 9 6450-6462. 2018.
  • 9.Shinohara, Y., Koyama, Y.M., Ukai-Tadenuma, M., Hirokawa, T., Kikuchi, M., Yamada, R.G., Ukai, H., Fujishima, H., Umehara, T., Tainaka, K. and Ueda, H.R.:
    "Temperature-sensitive substrate and product binding underlie temperature-compensated phosphorylation in the clock"
    Mol. Cell. 67 783-798. 2017.
  • 10.Niwa, H. and Umehara, T.:
    "Structural insight into inhibitors of flavin adenine dinucleotide-dependent lysine demethylases"
    Epigenetics. 12 340-352. 2017.

Related Links

Lab Members

Principal investigator

Takashi Umehara
Team Leader

Core members

Hideaki Niwa
Senior Technical Scientist
Masaki Kikuchi
Research Scientist
Nando Das
Research Scientist
Satoshi Morita
Technical Scientist
Masatoshi Wakamori
Technical Scientist
Shin Sato
Technical Scientist
Hisami Watanabe
Technical Scientist
Mie Goto
Technical Scientist
Daisuke Aoki
Junior Research Associate
Yuki Saito
Assistant

Contact Information

W221 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
Tel: +81-(0)45-503-9457
Fax: +81-(0)45-503-9201
Email: takashi.umehara [at] riken.jp

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