Laboratory for Human Disease Model
Group Director
Fumihiko ISHIKAWA
(M.D., Ph.D.)
Current understanding of mammalian stem cell biology and immunology has largely come from the studies using murine bone marrow, spleen and thymus. However, it is becoming increasingly apparent that many aspects of human stem cells and immune system are different from those in the mouse, making clinical translation of the knowledge gained from mouse research difficult. In order to establish novel stem cell therapies and immunotherapies, direct in vivo examination of human immune system is required. To this end, we have successfully developed immunologically humanized mice, and are currently developing various models of human diseases by using techniques such as transplantation of genetically modified stem cells and malignant stem cells into newborn immunodeficient mice.
- Purification of human hematopoietic stem cells and development of humanized mouse
- Identification of cancer stem cells
- Development of humanized mouse models for primary immunodeficiency diseases
- February 15, 2010
- Mechanism clarified governing anticancer drug resistance of leukemia relapse-triggering leukemia stem cells
- February 4, 2010
- Molecular target identified in leukemia stem cell that causes regeneration of acute myeloid leukemia
- January 14, 2011
- Towards a radical treatment for leukemia
- 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 exprtessing NOD/SCID/IL2rγnull humanized mice."
Proceedings of the National Academy of Science of the United States of America 107-29:13022-13027, 2010. - 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
"Cell cycle entry potentiates elimination of quiescent chemotherapy-resistant human AML stem cells."
Nature Biotechnology 28-3:275-280, 2010. - 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."
Science Translational Medicine 2-17: 17 ra 9, 2010. - Kong Y, Yoshida S, Saito Y, Doi T, Nagatoshi Y, Fukuta M, Saito N, Yang SM, Iwamoto C, Okamura J, Liu KY, Huang XJ, Lu DP, Shultz LD, Harada M, Ishikawa F
"CD34+CD38+CD19+ as well as CD34+CD38-CD19 cells are leukemia-initiating cells with self-renewal capacity in human B-precursor ALL."
Leukemia 22:1207-1213, 2008. - Ishikawa F, Saito Y, Shultz LD,
"Modeling human leukemia using immune-compromised mice. In "Mouse Models of Human Blood Cancer:Basic Research and Pre-Clinical Applications(Li,S,Editor)"."
Springer Science+Business Media, LLC, New York, 2008 - Saito Y and Ishikawa F
"The Origin of Blood: Induction of hematopoietic stem cells from different sources."
Cell Stem Cell: 8-10, 2008 - 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."
Nature Biotechnol 25: 1315-1321, 2007. - Ishikawa F, Niiro H, Iino T, Yoshida S, Saito N, Onohara S, Miyamoto T, Miyagawa H, Fujii SI, Shultz LD, Harada M, Akashi K.
"The developmental program of human dendritic cells is operated indeoendently of conventional myeloid and lymphoid pathways."
Blood 119: 3591-3660, 2007 - Shultz LD, Ishikawa F, Greiner DL.
"Humanized mice in translational biomedical research"
Nature Reviews Immunol , 7:118-130,2007.
Principal Investigator
- Fumihiko ISHIKAWA
- Group Director
Members
- Yoriko SAITO
- Mariko MURASAWA
- Nahoko SUZUKI
- Hiroshi KAJITA
- Ikuko OGAHARA
- Yuki AOKI
- Shinsuke TAKAGI
- Yuho NAJIMA
- Satoshi TANAKA
- Visiting Scientist