Laboratory for Epigenetics Drug Discovery | RIKEN BDR

Laboratory for Epigenetics Drug Discovery

Team Leader

Takashi UmeharaPh.D.

  • Location:Yokohama / West Bldg. W221
  • E-mail:takashi.umehara[at]riken.jpPlease replace [at] with @.

Change “added” life info as you like

Research Summary

Epigenetics is a research field that tackles life information that is "added" to genetic information. The major entity of this "addition" is a chemical modification to a complex of a genomic DNA and histone proteins called chromatin. Since epigenetics is involved in the control of cancer, iPS cells and lifespan, it attracts attention as a molecular target for drug discovery, regenerative medicine, and anti-aging. Our laboratory aims to manipulate diseases, iPS cells and anti-aging as desired by developing technologies to precisely reconstitute, detect and control human epigenetic information.

Reconstitution of epigenetics
Synthetic technologies of a protein acetylated as designed. With this technology, transcriptionally active chromatin can be precisely reproduced in vitro.

Detection of epigenetics
Development of an antibody that detects acetylation at two residues in histone H4 tail. With this antibody, transcriptionally hyperactive chromatin can be detected at single nucleosome resolution.

Regulation of epigenetics
Histone demethylase inhibitor S2101 developed based on protein structure. This compound is commercially available as an epigenetics-regulating reagent.

Research Theme

  • In vitro reconstitution of epigenetics and its application (Synthetic Biology)
  • Understanding of molecular basis and regulatory mechanism of epigenetics (Structural Biology)
  • Development of regulators of epigenetic and genetic information (Drug Discovery)

Main Publications List

  • Saito S, Kikuchi J, Koyama D, et al.
    Eradication of central nervous system leukemia of T-cell origin with a brain-permeable LSD1 inhibitor.
    Clinical Cancer Research 25. 1601-1611 (2019) doi: 10.1158/1078-0432.CCR-18-0919
  • Umezawa N, Tsuji K, Sato S, et al.
    Inhibition of FAD-dependent lysine-specific demethylases by chiral polyamine analogues.
    RSC Advances 8. 36895-36902 (2018) doi: 10.1039/c8ra07879c
  • Tsusaka T, Kikuchi M, Shimazu T, et al.
    Tri-methylation of ATF7IP by G9a/GLP recruits the chromodomain protein MPP8.
    Epigenetics & Chromatin 11. 56 (2018) doi: 10.1186/s13072-018-0231-z
  • Handoko L, Kaczkowski B, Hon CC, et al.
    JQ1 affects BRD2-dependent and independent transcription regulation without disrupting H4-hyperacetylated chromatin states.
    Epigenetics 13. 410-431 (2018) doi: 10.1080/15592294.2018.1469891
  • Osada N, Kikuchi J, Umehara T, et al.
    Lysine-specific demethylase 1 inhibitors prevent teratoma development from human induced pluripotent stem cells.
    Oncotarget 9. 6450-6462 (2018) doi: 10.18632/oncotarget.24030
  • Shinohara Y, Koyama YM, Ukai-Tadenuma M, et al.
    Temperature-sensitive substrate and product binding underlie temperature-compensated phosphorylation in the clock.
    Molecular Cell 67. 783-798 (2017) doi: 10.1016/j.molcel.2017.08.009
  • Niwa H, Umehara T.
    Structural insight into inhibitors of flavin adenine dinucleotide-dependent lysine demethylases.
    Epigenetics 12. 340-352 (2017) doi: 10.1080/15592294.2017.1290032
  • Takemoto Y, Ito A, Niwa H, et al.
    Identification of cyproheptadine as an inhibitor of SET domain containing lysine methyltransferase 7/9 (Set7/9) that regulates estrogen-dependent transcription.
    Journal of Medicinal Chemistry 59. 3650-3660 (2016) doi: 10.1021/acs.jmedchem.5b01732
  • Kashiwagi K, Takahashi M, Nishimoto M, et al.
    Crystal structure of eukaryotic translation initiation factor 2B.
    Nature 531. 122-125 (2016) doi: 10.1038/nature16991
  • Wakamori M, Fujii Y, Suka N, et al.
    Intra- and inter-nucleosomal interactions of the histone H4 tail revealed with a human nucleosome core particle with genetically-incorporated H4 tetra-acetylation.
    Scientific Reports 5. 17204 (2015) doi: 10.1038/srep17204

All Publications


Takashi UmeharaTeam Leader takashi.umehara[at] CV
Hideaki NiwaSenior Technical Scientist* hideaki.niwa[at]
Masaki KikuchiResearch Scientist masaki.kikuchi[at]
Nando Dulal DasResearch Scientist nando.das[at]
Satoshi MoritaTechnical Scientist satoshi.morita[at]
Masatoshi WakamoriTechnical Scientist masatoshi.wakamori[at]
Shin SatoTechnical Scientist shin.sato[at]
Hisami WatanabeTechnical Scientist hisami.watanabe[at]
Mie GotoTechnical Scientist mie.goto[at]
Daisuke AokiJunior Research Associate daisuke.aoki[at]
Yuki SaitoAssistant yuki.saito[at]

*:concurrent / Please replace [at] with @.