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Prof. Kazuhiro Nagata
Assoc. Prof. Nobuko Hosokawa
Assist. Prof. Hiroshi Kubota
Stress proteins/molecular chaperones are essential protein families for the maintenance of homeostasis and for the
regulation of various cellular functions. Our main interest is focused on the regulation and function of stress proteins/
molecular chaperones in teams of development and tissue regeneration. Kazuhiro Nagata found a novel collagen-specific
molecular chaperone HSP47, and revealed that HSP47 is essential chaperone for correct folding and secretion of collagen
molecules. Recently, Nobuko Hosokawa found and cloned a novel mannosidase-like protein, EDEM, which accelerates
the ER (endoplasmic reticulum)-associated degradation of misfolded proteins in the ER and is expected to be a key
molecule in the quality control mechanism in the ER. The third project in our lab is the regulation and function of
cytoplasmic chaperonin CCT. Hiroshi Kubota found and cloned all of the cDNAs and genomic DNAs of 8 subunits of CCT,
and we recently found that CCT prevents the aggregate formation of poly-glutamine repeat proteins in the cytosol and
prevents the neuronal cell death due to the aggregate formation.
Lect. Kazunori Hirayosi
Almost all phenomenon of life is regulated by gene expression depending on the time and place. Understanding of
gene regulation leads to realize the total regulation of life. Methods for the analysis of transcriptional regulation used be
based on the in vitro analysis focused on the function of specific transcription factors, is changing to focus on the dynamic
regulation including the change of chromatin structure in vivo. To analyze the gene regulation in vivo, we introduce an
RNA aptamer. RNA aptamers consist of around 100 nt and make its own tertiary structure for expressing their function
as a specific inhibitor on the spot. Using this feature, we focus on three major issues. 1) Architecture of transcription
complex. 2) The effect of chromatin remodeling factors on the transcription. 3) Establishment of new evaluation system
and application of RNA aptamer, which is an innovative methodology we used for the analysis of transcription.
Prof. Shimon Sakaguchi
Assist. Prof. Takashi Nomura
Assist. Prof. Takatoku Oida
We are studying (i) the cellular and molecular basis of immunologic self-tolerance and autoimmune
disease as its abnormality ; (ii) the strategy for eliciting effective immune responses to autologous tumor
cells or inducing acceptance of organ transplants by manipulating the mechanism of immunologic selftolerance
; and (iii) the cause and pathogenetic mechanism of rheumatoid arthritis by analyzing a newly
established mouse model of autoimmune arthritis.
Prof. Takashi Nagasawa
Chemokines are structurally related small chemoattractive cytokines. We isolated a chemokine, CXCL12 (SDF-1/
PBSF) as a molecule that stimulates the growth of B lymphocyte precursors and have found its multiple physiological
functions in development. We have shown that the primary physiologic receptor for CXCL12 is CXCR4, which also functions
as a coreceptor for strains of HIV-1 and that CXCL12-CXCR4 signaling is essential for colonization of bone marrow
by hematopoietic cells including hematopoietic stem cells (HSCs), colonization of gonads by primordial germ cells (PGCs)
during ontogeny, maintenance of a pool of HSCs in adult bone marrow, development of B lymphocytes, vascularization of
the gastrointestinal tract and cardiogenesis. In recent years, we have identified a population of reticular cells, which
express CXCL12 at high levels, termed CXCL12 abundant reticular (CAR) cells within bone marrow and suggested that
CAR cells function as the special microenvironment niches for HSCs and B lymphocytes and that CXCL12 maintains the
stem cells or precursors in the niche. We are studying the roles of CXCL12-CXCR4 signaling and CAR cells in hematopoiesis
to understand the spatiotemporal regulation of lymphohematopoiesis by environmental factors within bone marrow.
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Human Embryonic Stem Cell Project
