Centers & Labs

RIKEN Center for Integrative Medical Sciences

Laboratory for Integrated Cellular Systems

Team Leader: Mariko Okada (Ph.D.)
Mariko  Okada(Ph.D.)

The Laboratory for Cellular Systems Modeling has been carrying out research to identify biological networks and its regulatory principles using computational, theoretical and experimental approaches. Our research interest is to identify and reconstruct biological regulatory circuits from experimentally observable data using computational and theoretical approaches to unveil the complexity of signal transduction networks, which determine cell fate in mammalian cells. By doing this, we are able to identify rules specified in immunological systems or in cancer.

Main Research Field

Biology & Biochemistry

Related Research Fields

Engineering / Molecular Biology & Genetics / Computer Science

Research Subjects

  • Systems Biology of signal-transcription network
  • Integration of Omics data
  • Modeling of cell fate

Selected Publications

  1. 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:
    "TAK1-IKKβ positive feedback enforced by CARMA1 functions as a switch mechanism for NF-κB activation."
    Science , 44(6185) 760-764 (2014).
  2. Kajiyama, K., Okada-Hatakeyama, M., Hayashizaki, Y., Kawaji, H. and Suzuki, H.:
    "Capturing drug responses by quantitative promoter activity profiling."
    CPT: Pharmacometrics & Systems Pharmacology, 2, e77; doi:10.1038/psp.2013.53. (2013)
  3. Hiroshima, M., Saeki, Y., Okada-Hatakeyama, M., and Sako, Y.:
    "Dynamically varying interactions between heregulin and ErbB proteins detected by single-molecule analysis in living cells."
    Proc. Natl. Acad. Sci. U.S.A. 109 (35) 13984-13989. (2012)
  4. Oyama, M., Nagashima, T., Suzuki, T., Kozuka-Hata, H., Yumoto, N., Shiraishi, Y., Ikeda, K., Kuroki, Y., Gotoh, N., Ishida, T., Inoue, S., Kitano, H., and Okada-Hatakeyama, M.:
    "Integrated quantitative analysis of the phosphoproteome and transcriptome in tamoxifen-resistant breast cancer."
    J. Biol. Chem. 286, 818-829. (2011)
  5. Nakakuki, T., Birtwistle, MR., 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, 884-896. (2010)
  6. 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)
  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. Mina, M., Magi, S., Hayashizaki, Y., Lassmann, T., Carninci, P., Arner, E., Itoh, M., Kawaji, H., The FANTOM consortium、Forrest, A., Jurman, G., Daub, C., Okada-Hatakeyama, M., Furlanello, C.:
    "Promoter-level expression clustering identifies time development of transcriptional regulatory cascades initiated by ErbB receptors in breast cancer cells"
    Scientific reports 16;5:11999. (2015)

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