Centers & Labs

RIKEN Center for Integrative Medical Sciences

Laboratory for Human Disease Models

Team Leader: Fumihiko Ishikawa (M.D., Ph.D)
Fumihiko  Ishikawa(M.D., Ph.D)

We have been trying to understand human hematopoietic and immune systems by creating “humanized mice”. This system has enabled us to analyze how human hematopoietic stem cells generate their progeny and how human immune subsets become mature and functional in organs such as bone marrow, spleen, and thymus.
In addition to the understanding of normal human blood and immune systems, we have succeeded in recapitulating human leukemic status in mice. Using the humanized mice for leukemia, we have clarified a mechanism underlying relapse in acute myeloid leukemia and identified several potential therapeutic targets in chemotherapy-resistant human leukemic stem cells. Through multi-faceted approach, we are currently developing new and effective treatment strategies for helping patients with poor prognosis leukemia.

Main Research Field

Medicine, dentistry, and pharmacy

Related Research Fields

Biological Sciences

Keywords

  • Hematopoietic stem cell
  • Leukemia stem cell
  • Humanized mouse
  • Human immunology

Selected Publications

  1. Saito Y, Mochizuki Y, Ogahara I, Watanabe T, Hogdal L, Takagi S, Sato K, Kaneko A, Kajita H, Uchida N, Fukami T, Shultz LD, Taniguchi S, Ohara O, Letai AG, Ishikawa F.:
    "Overcoming mutational complexity in acute myeloid leukemia by inhibition of critical pathways"
    Science Translational Medicine eaao1214, 2017.
  2. Najima Y, Tomizawa- Murasawa M, Saito Y, Watanabe T, Ono R, Ochi T, Suzuki N, Fujiwara H, Ohara O, Shultz LD, Yasukawa M, Ishikawa F.:
    "Induction of WT1-specific human CD8+ T cells from human HSCs in HLA class I Tg NOD/SCID/IL2rgKO mice"
    Blood 127 , 722-34, 2016
  3. Aoki Y, Watanabe T, Saito Y, Kuroki Y, Hijikata A, Takagi M, Tomizawa D, Eguchi M, Eguchi-Ishimae M, Kaneko A, Ono R, Sato K, Suzuki N, Fujiki S, Koh K, Ishii E, Shultz LD, OharaO, Mizutani S, Ishikawa F.:
    "Identification of CD34+ and CD34- leukemia-initiating cells in MLL-rearranged human acute lymphoblastic leukemia"
    Blood 125, 967-80, 2015.
  4. Saito Y, Yuki H, Kuratani M, Hashizume Y, Takagi S, Honma T, Tanaka A, Shirouzu M, Mikuni J, Handa N, Ogahara I, Sone A, Najima Y, Tomabechi Y, Wakiyama M, Uchida N, Tomizawa-Murasawa M, Kaneko A, Tanaka S, Suzuki N, Kajita H, Aoki Y, Ohara O, Shultz LD, Fukami T, Goto T, Taniguchi S, Yokoyama S and Ishikawa F.:
    "A Pyrrolo-Pyrimidine Derivative Targets Human Primary AML Stem Cells in Vivor"
    Sci Transl Med 5, 181ra52, 2013.
  5. Takagi S, Saito Y, Hijikata A, Tanaka S, Watanabe T, Hasegawa T, Mochizuki S, Kunisawa J, Kiyono H, Koseki H, Ohara O, Saito T, Taniguchi S, Shultz LD, Ishikawa F.:
    "Membrane-bound human SCF/KL promotes in vivo human hematopoietic engraftment and myeloid differentiation."
    Blood 119, 2768-2777, 2012.
  6. Shultz LD, Saito Y, Najima Y, Tanaka S, Ochi T, Tomizawa-Murasawa M, Doi T, Sone A, Suzuki N, Fujiwara H, Yasukawa M, Ishikawa F.:
    "Generation of functional human T-cell subsets with HLA-restricted immune responses in HLA class I expressing NOD/SCID/IL2rγnull humanized mice."
    Proc Natl Acad of Sci U S A 107, 13022-7, 2010.
  7. Saito Y, Uchida N, Tanaka S, Suzuki N, Tomizawa-Murasawa M, Sone A, Najima Y, Takagi S, Aoki Y, Wake A, Taniguchi S, Shultz LD, Ishikawa F.:
    "Induction of cell cycle entry eliminates human leukemia stem cells in a mouse model of AML"
    Nat Biotechnol 28, 275-80, 2010.
  8. Saito Y, KitamuraH, Hijikata A, Tomizawa-Murasawa M, Tanaka S, Takagi S, Uchida N, Suzuki N, Sone A, Najima Y, Ozawa H, Wake A, Taniguchi S, Shultz LD, Ohara O, Ishikawa F.:
    "Identification for therapeutic targets for quiescent chemotherapy-resistant human AML stem cells"
    Sci Transl Med 2, 17ra9, 2010.
  9. Ishikawa F, Yoshika S, Saito Y, Hijikata A, Kitamura H, Tanaka S, Nakamura R, Tanaka T, Tomiyama H, Saito N, Fukata M, Miyamoto T, Lyons B, Ohshima K, Uchida N, Taniguchi S, Ohara O, Akashi K, Harada M, Shultz LD.:
    "Chemotherapy-resistant human AML stem cells home to and engraft within the bone marrow endosteal region"
    Nat Biotechnol 25, 1315-21, 2007.
  10. Shultz LD, Ishikawa F, Greiner DL.:
    "Humanized mice in translational biomedical research"
    Nat Rev Immunol 7, 118-30, 2007.

Lab Members

Principal Investigator

Fumihiko Ishikawa
Team Leader

Core Members

Yoriko Saito
Senior Research Scientist
Rintaro Ono
Junior Research Associate
Kaori Sato
Technical Staff I
Ikuko Ogahara
Technical Staff I
Hiroshi Kajita
Technical Staff II
Nahoko Suzuki
Technical Staff II
Saera Fujiki
Technical Staff II
Akiko Kaneko
Technical Staff II

Contact information

1-7-22 Suehiro-cho, Tsurumi-ku,
Yokohama City, Kanagawa,
230-0045, Japan
Tel: +81-(0)45-503-9448
Fax: +81-(0)45-503-7068

Email: fumihiko.ishikawa [at] riken.jp

Related links

Recent research results