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RIKEN Center for Integrative Medical Sciences Laboratory for Integrated Cellular Systems

Team Leader: Mariko Okada (Ph.D.)

Research Summary

Mariko  Okada(Ph.D.)

Mammalian signal transduction pathways transfer a variety of extracellular information to transcription factors in the nucleus to regulate gene expression and cell fate. The aims of the laboratory are to define the general regulatory logics in signal transduction-transcriptional networks to apply this knowledge of regulatory principles to the understanding and treatment of human diseases. Particularly, we focus on the time-course process on signal-dependent early transcriptional regulation in proliferation or differentiation of cancer and immune cells. Our laboratory uses both wet-lab (cell biology, molecular biology, biochemistry) and dry-lab approaches (bioinformatics, computation, mathematics) to solve this question.

Main Research Fields

  • Biology

Related Research Fields

  • Informatics
  • Complex Systems
  • Interdisciplinary Science & Engineering
  • Mathematical & Physical Sciences
  • Biological Sciences


  • Signal transduction
  • Mathematical modeling
  • Transcriptional regulation
  • Omics data integration

Selected Publications

  • 1.Magi, S., Iwamoto, K., and Okada-Hatakeyama, M.:
    "Current Status of Mathematical Modeling of Cancer – From the Viewpoint of Cancer Hallmarks."
    Current Opinion in Systems Biology. 2:38-47 (2017).
  • 2.Domínguez-Hüttinger, E., Christodoulides, P., Miyauchi, K., Irvine, A.D., Okada-Hatakeyama, M., Kubo, M., and Tanaka, R.J.:
    "Mathematical modeling of atopic dermatitis reveals "double-switch" mechanisms underlying 4 common disease phenotypes."
    J. Allergy Clin. Immunol. pii: S0091-6749(16)31433-6 (2016)
  • 3.Mina, M., Magi, S., Jurman, G., Itoh, M., Kawaji, H., Lassmann, T., Arner, E., Forrest, A.R.R., Carninci, P., Hayashizaki, Y., Daub, C.O., the FANTOM Consortium, Okada-Hatakeyama, M., and Furlanello, C.:
    "Promoter-level expression clustering identifies time development of transcriptional regulatory cascades initiated by ErbB receptors in breast cancer cells."
    Sci. Rep. 5:11999. doi: 10.1038/srep11999 (2015).
  • 4.Nagashima, T., Inoue, N., Yumoto, N., Saeki, Y., Magi, S., Volinsky, N., Sorkin, A., Kholodenko, B.N. and Okada-Hatakeyama, M.:
    "Feedforward regulation of mRNA stability by prolonged ERK activity."
    FEBS J. 282(4), 613-629 (2015).
  • 5.Shinohara, H., Behar, M., Inoue K., Hiroshima, M., Yasuda, T., Nagashima, T., Kimura, S., Sanjo, H., Maeda, S., Yumoto, N., Ki, S., Akira, S., Sako, Y., Hoffmann, A., Kurosaki, T., and Okada-Hatakeyama, M.:
    "Positive feedback within a kinase signaling complex functions as a switch mechanism for NF-κB activation."
    Science 344(6185): 760-764 (2014).
  • 6.Nakakuki, T., Birtwistle, M.R., Saeki, Y., Yumoto, N., Ide, K., Nagashima, T., Brusch, L., Ogunnaike, B.A., Okada-Hatakeyama, M., and Kholodenko, B.N.:
    "Ligand-specific c-Fos expression emerges from the spatiotemporal control of ErbB network dynamics."
    Cell 141(5): 884-896, 2010.
  • 7.Nagashima, T., Shimodaira, H., Ide, K., Nakakuki, T., Tani, Y., Takahashi, K., Yumoto, N., and Hatakeyama, M.:
    "Quantitative transcriptional control of ErbB receptor signaling undergoes graded to biphasic response for cell differentiation."
    J. Biol. Chem. 282, 4045-4056. (2007)
  • 8.Kimura, S., Ide, K., Kashihara, A., Kano, M., Hatakeyama, M., Masui, R., Nakagawa, N., Yokoyama, S., Kuramitsu, S., and Konagaya, A.:
    "Inference of S-system models of genetic networks using a cooperative coevolutionary algorithm."
    Bioinformatics 21, 1154-1163. (2005)
  • 9.Hatakeyama, M., Kimura, S., Naka, T., Kawasaki, T., Yumoto, N., Ichikawa, M., Kim, J-H., Saito, K., Saeki, M., Shirouzu, M., Yokoyama, S. and Konagaya, A.:
    "A computational model on the modulation of MAPK and Akt pathways in heregulin induced ErbB signaling."
    Biochem. J. 373, 451-463. (2003)
  • 10.Birtwistle, M.R., Hatakeyama, M., Yumoto, N., Ogunnaike, B.A., Hoek, J.B., and Kholodenko, B.N.:
    "Ligand-dependent responses of the ErbB signaling network: experimental and modeling analysis."
    Mol. Syst. Biol. 3:144 (2007)

Recent Research Results

Related Links

Lab Members

Principal investigator

Mariko Okada
Team Leader

Core members

Hisaaki Shinohara
Senior Research Scientist
Kazunari Iwamoto
Research Scientist
Shigeyuki Magi
Research Scientist
Kentaro Inoue
Research Scientist

Contact Information

1-7-22 Suehiro-cho, Tsurumi-ku,
Yokohama City, Kanagawa,
230-0045, Japan

Email: marikoh [at] riken.jp