Laboratory for Epigenetics Drug Discovery | RIKEN BDR

Laboratory for Epigenetics Drug Discovery

Team Leader

Takashi UmeharaPh.D.

Photo of principal investigator

  • 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

  • Wakamori M, Okabe K, Ura K, et al.
    Quantification of the effect of site-specific histone acetylation on chromatin transcription rate.
    Nucleic Acids Research gkaa1050 (2020) doi: 10.1093/nar/gkaa1050
  • Takahashi R, Sakamoto K, Umezawa N, et al.
    Chemoselective arylation of dialkyl diselenides and its application to synthesis of a ε-N,N,N-trimethyllysine derivative.
    European Journal of Organic Chemistry 2020. 6649-6652 (2020) doi: 10.1002/ejoc.202001208
  • Wu HD, Kikuchi M, Dagliyan O, et al.
    Rational design and implementation of a chemically inducible hetero-trimerization system.
    Nature Methods 17. 928-936 (2020) doi: 10.1038/s41592-020-0913-x
  • Furukawa A, Wakamori M, Arimura Y, et al.
    Acetylated histone H4 tail enhances histone H3 tail acetylation by altering their mutual dynamics in the nucleosome.
    Proceedings of the National Academy of Sciences USA 117. 19661-19663 (2020) doi: 10.1073/pnas.2010506117
  • Aoki D, Awazu A, Fujii M, et al.
    Ultrasensitive change in nucleosome binding by multiple phosphorylations to the intrinsically disordered region of the histone chaperone FACT.
    Journal of Molecular Biology 432. 4637-4657 (2020) doi: 10.1016/j.jmb.2020.06.011
  • Shirai F, Mizutani A, Yashiroda Y, et al.
    Design and discovery of an orally efficacious spiroindoline-based tankyrase inhibitor for the treatment of colon cancer.
    Journal of Medicinal Chemistry 63. 4183-4204 (2020) doi: 10.1021/acs.jmedchem.0c00045
  • Niwa H, Sato S, Handa N, et al.
    Development and structural evaluation of N-alkylated trans-2-phenylcyclopropylmine-based LSD1 inhibitors.
    ChemMedChem 15. 787-793 (2020) doi: 10.1002/cmdc.202000014
  • Shirai F, Tsumura T, Yashiroda Y, et al.
    Discovery of novel spiroindoline derivatives as selective tankyrase inhibitors.
    Journal of Medicinal Chemistry 62. 3407-3427 (2019) doi: 10.1021/acs.jmedchem.8b01888
  • 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
  • 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

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]
Daisuke AokiResearch Fellow daisuke.aoki[at]
Yuki SaitoAssistant yuki.saito[at]

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