Technology and Development Team for BioSignal Program
Technology and Development Team for BioResponse Program Subteam for Biosignal Integration
Subteam Leader
Takahiro DOI (M.D.)
Organisms always receive stimulation from outside and maintain themselves in response to such stimulation through the complex network of signal transduction. Analysis of this mechanism is the way to elucidate bio response mechanism and to characterize bioresource materials. The main goal of our subteam is to develop new techniques for elucidation of signal transduction mechanism on bio response through the analysis of gene and protein expression using microchip array technique and database at each step including genes, cells, tissues and whole bodies. And the other goal is elucidation of the effect toward lives by abnormal cytokine networks and the mechanisms of diseases including cancers through analysis of signal transduction pathways of cytokines. Furthermore it's the another goal of ours is to develop the model mice for human diseases with the reconstruction of abnormal networks in vivo in the base of the bioinformation stored in BRC for the more detailed study and development of the new treatment for those diseases. We focus on characterization of NF-κB and Tumor necrosis factor (TNF) for analysis of signal transduction mechanisms in lives.
- Analyssi of the regulatory mechanism for lymphopoiesis with NF-kB/RelA
- Analyssi of the regulatory mechanism for bone metabolism with NF-kB/RelA
- Analyssi of the regulatory mechanism for autoimmunity with NF-kB/RelA
- Analyssi of the regulatory mechanism for hematopoiesis with NF-kB/RelA
- Analyssi of the regulatory mechanism for inflammation with NF-kB/RelA
- Nakano H, Doi T et al.:
"Oxidative stress-dependent production of Interleukin 11 ameliorates drug-induced murine hepatitis through compensatory proliferation."
Journal of Clinical Investigation (2011) - Maruyama T, Fukushima H, Nakao K, Shin M, Yasudsa H, Weih F, Doi T, Aoki K, Ohya K, Hsokawa R and Jimi E:
"Processing of the NF-kB2 precursor, p100, to p52 is critical for RANKL-induced osteoclast differentiation"
Journal of Bone and Mineral Research (2009) - Yamazaki M, Fukushima H, Shin M, Katagiri T, Doi T, Takahashi T and Jimi E:
"A proximal kappaB site in the IL-23 p19 promoter is responsible for RelA- and c-Rel-dependent transcription"
Journal of Biological Chemistry, 284; 35987-95 (2009) - Mise-Omata S, Kuroda E, Sugiura T, Yamashita U, Obata Y, and Doi TS:
"The NF-kB RelA subunit confers resistance to Leishmania major by inducing NOS2 and Fas expression but not Th1 differentiation"
J. Immunol. 182;4910-4916 (2009) - Mise-Omata S, Kuroda E, Niikura J, Yamashita U, Obata Y, and Doi TS:
"A proximal kappaB site in the IL-23 p19 promoter is responsible for RelA- and c-Rel-dependent transcription"
J. Immunol. 179, 6596-6603 (2007). - Kuroda E, Noguchi J, Doi TS, Uematsu S, Akira S and Yamashita U:
"IL-3 is an important differentiation factor for the development of prostaglandin E2-producing macrophages between C57BL/6 and BALB/c mice."
European J. Immunol. 37, 2185-2195 (2007) - Pia JH, Yoshida H, Yeh WC, Doi TS, Xue X, Yagita H, Okumura K, and Nakano H:
"TRAF2-dependent canonical pathway is critical for the development of peyer's patches."
J. Immunol. 178, 2272-2277 (2007). - Akashi-Takamura S, Doi H, Takahashi K, Tanimura N, Saitoh S, Adachi Y, Doi TS, Shimozato T, and Miyake K:
"Agonistic Antibody to Toll-like receptor 4/MD-2 Protects Mice from Acute Lethal Hepatitis Induced by Tumor Necrosis Factor."
J. Immunol. 176, 4244-4251 (2006). - Mise-Omata S, Iwase S, Mise N, Obata Y and Doi TS:
"Transient strong reduction of PTEN expression by specific RNAi induces loss of adhesion of the cells"
Biochem. Biophy. Res. Comm. 328, 1043-1042 (2005) - Mattioli I, Sebald A, Bucher C, Charles RP, Nakano H, Doi TS, Kracht M, and Schmitz M.L.:
"Transient and selective NF-kappa B p65 serine 536 phosphorylation induced by T cell costimulation is mediated by I kappa B kinase beta and controls the kinetics of p65 nuclear import"
J. Immunol. 172, 6336-6344 (2004).
Technology and Development Team for Biosignal Program Subteam for Maniputation of Cell Fate
Subteam Leader
Hiroyuki MIYOSHI (D.Sci.)
Stem cells are defined as undifferentiated cells capable of making identical copies of themselves and giving rise to specialized cells that make up the tissues and organs of the body. In recent years, stem cells have received much attention for their use in regenerative therapy. However, before stem cells can be used clinically, it is important to understand the fundamental mechanisms that regulate proliferation and differentiation of stem cells. Our group seeks to identify the signaling pathways that control stem cell fate and hopes to develop technologies for manipulating stem cells in vitro.
- Studies on the proliferation and differentiation of hematopoietic stem cells
- Studies on the replicative capacity and aging of stem cells
- Development of lentiviral vectors for stem cell biology
- Inoue, S., Noda, S., Kashima, K., Nakada, K., Hayashi, J., and Miyoshi, H.:
"Mitochondrial respiration defects modulate differentiation but not proliferation of hematopoietic stem and progenitor cells."
FEBS Lett. 584, 3402-3409 (2010) - Noda, S., Ichikawa, H., and Miyoshi, H.:
"Hematopoietic stem cell aging is associated with functional decline and delayed cell cycle progression."
Biochem. Biophys. Res. Commun. 383, 210-215 (2009) - Shimizu, N., Noda, S., Katayama, K., Ichikawa, H., Kodama, H., and Miyoshi, H.:
"Identification of genes potentially involved in supporting hematopoietic stem cell activity of stromal cell line MC3T3-G2/PA6."
Int. J. Hematol. 87, 239-245 (2008) - Noda, S., Horiguchi, K., Ichikawa, H., and Miyoshi, H.:
"Repopulating activity of ex vivo-expanded murine hematopoietic stem cells resides in the CD48-c-Kit+Sca-1+lineage marker- cell population."
Stem Cells 26, 646-655 (2008) - Inoue, S., Yokota, M., Nakada, K., Miyoshi, H., and Hayashi, J.:
"Pathogenic mitochondrial DNA-induced respiration defects in hematopoietic cells result in anemia by suppressing erythroid differentiation."
FEBS Lett. 581, 1910-1916 (2007) - Inoue, K., Noda, S., Ogonuki, N., Miki, H., Inoue, S., Katayama, K., Mekada, K., Miyoshi, H., and Ogura, A.:
"Differential developmental ability of embryos cloned from tissue-specific stem cells."
Stem Cells 25, 1279-1285 (2007) - Inoue, S., Ishikawa, K., Nakada, K., Sato, A., Miyoshi, H., and Hayashi, J.:
"Suppression of disease phenotypes of adult mito-mice carrying pathogenic mtDNA by bone marrow transplantation."
Hum. Mol. Genet. 15, 1801-1807 (2006) - Inoue, K., Ogonuki, N., Miki, H., Hirose, M., Noda, S., Kim, J. M., Aoki, F., Miyoshi, H., and Ogura, A.:
"Inefficient reprogramming of the hematopoietic stem cell genome following nuclear transfer."
J. Cell Sci. 119, 1985-1991 (2006) - Miyoshi, H., Smith, K.A., Mosier, D.E., Verma, I.M., and Torbett, B.E.:
"Transduction of human CD34+ cells that mediate long-term engraftment of NOD/SCID mice by HIV vectors."
Science 283, 682-686 (1999) - Miyoshi, H., Blomer, U., Takahashi, M., Gage, F. H., and Verma, I. M.:
"Development of a self-inactivating lentivirus vector."
J. Virol. 72, 8150-8157 (1998)