Laboratory of Environmental MolecularPhysiology 

    School of Life Sciences
Tokyo University of Pharmacy and
Life Sciences


Yuji Takahashi, PhD yuji,xx,
Shigeru Takahashi,PhD shigeru,xx,
Mariko Umemura, PhD mumemura,xx,
Haruo Nakano, PhD haruo,xx,


 The activities of more than 7 billion people on earth have made a huge impacton the global and local environment, resulting in physical and chemical stress toliving organisms.  Our laboratory has focused on exploring the molecularmechanism by which metazoa, mammals and molluscs in particular, respond tothese environmental stresses.

I. Regulation of gene expression in stress-response processes of mammalian cells.

We have identified Activating Transcription Factor 5 (ATF5) as a stress-responsive transcription factor regulated in oxidative and nutritional stresses. We have been examining the gene expression mechanisms of ATF5 in steps of transcription, mRNA stability, translation, and protein stability.

II. Physiological roles of stress responsive transcription factor

To explore the physiological roles of the stress-responsive transcription factor, we have examined phenotypes of genetically modified mice from developmental and behavioral aspects.

III. Ecotoxicological effects of environmental contaminants on marine molluscs

Man-made chemicals contaminate the marine environment. Organotincompounds: tributhyl tin andtriphenyl tin, have been used as antifouling paints andhave been polluting many species of marinegastropods (molluscs) leading toinduction of partial sex-reversal from female to male. We have studiedthemolecular mechanism by which organotin compounds cause this masculinization offemale snails.


Recent Publications

Abe T., Kojima M., AkanumaS., Iwashita H., Yamazaki T., Okuyama R., Ichikawa K., Umemura M., Nakano H.,
Takahashi S., Takahashi Y.  N-terminal hydrophobic amino acids of ATF5confer IL-1b-induced stabilization,

J Biol Chem, 289, 3888-3900 (2014)

Yun, Y.S., Noda, S., Shigemori, G., Kuriyama, R., Takahashi, S., Umemura, M., Takahashi, Y., Inoue, H.:
Phenolic diterpenes from rosemary suppress cAMP responsiveness of gluconeogenic gene promoters.
Phytother Res 27(6), 906-910 (2013)

Hatano M., Umemura M., Kimura N., Yamazaki T., Takeda H., Nakano H.,Takahashi S., Takahashi Y. The 5'-
untranslated region regulates ATF5 mRNAstability via nonsense-mediated mRNA decay in response to
environmentalstress.FEBS J.280, 4693-4707 (2013)

Nakano H., Ymamada Y., Miyazawa T., Yoshida T. Gain-of-function screeningidentify miR-193a regulating
proliferation and apoptosis in epithelial ovariancancer cells.Int. J. Oncol., 42, 1875-1882 (2013)

Lu J., Zhang S., Nakano H., Simmons D.G., Wang S., Kong S., Wang Q., Shen L.,Tu Z., Wang W., Wang B.,
Wang H., Wang Y., van Es J. H., Clevers H., Leone G.,Cross J.C., Wang H. A positive feedback loop involving
Gcm1 and Fzd5 directschorionic branching morphogenesis in the placenta.PLOS Biol., 11, e1001536(2013)

Yoko-O T., Ichikawa D., Miyagishi Y., Kato A., Umemura M., Takase K., Ra M.,Ikeda K., Taguchi R., Jigami
 Determination and physiological roles of theglycosylphosphatidylinositol lipid remodeling pathway in yeast.
Mol Microbiol.,88, 140-155 (2013)

Goto, Y., Kajiwara, M., Yanagisawa, Y., Hirose, H., Yoshimi, T., Umemura, M.,Nakano, H., Takahashi, S., Shida,
Y., Iguchi, T., Takahashi, Y., Miura T. Detectionof vertebrate-type sterid hormones and their converting
activity in theneogastropid, Thais clavigera.J. Mol. Studies
,  78, 197–204 (2012)

Yun YS, Noda S, Shigemori G, Kuriyama R, Takahashi S, Umemura M, TakahashiY, Inoue H. Phenolic
Diterpenes from Rosemary Suppress cAMPResponsiveness of Gluconeogenic Gene Promoters.Phytother
DOI: 10.1002/ptr.4794 (2012)

Asanuma-Date K., Hirano Y., Le N., Sano K., Kawasaki N., Hashii N., Hiruta Y.,Nakayama K., Umemura M.,
Ishikawa K., Sakagami H., Ogawa H. Functionalregulation of sugar assimilation by N-glycan-specific
interaction of pancreatic
a-Amylase with glycoproteins of duodenal brush border membrane.J Biol Chem.,
287, 23104-23118 (2012)

Haraguchi, T., Nakano H., Tagawa T., Ohki T., Ueno Y., Yoshida T., Iba H. Apotent 2’-O-methylated RNA-
based microRNA inhibitor with unique secondarystructures.Nucl. Acids Res., 40, e58 (2012).

Sagane, K., Umemura, M., Ogawa-Mitsuhashi, K., Tsukahara, K, Yoko-o, T.,Jigami, Y. Analysis of
membrane topology and identification of essentialresidues for the yeast endoplasmic reticulum inositol
acyltransferase gwt1p.J
.Biol.Chem., 286, 14649-14658 (2011).

Yamazaki, T., Ohmi, A., Kurumaya, H., Kato, K., Abe, T.,Yamamoto, H., Nakanishi, N.,
, R., Umemura, M., Kaise, T., Watanabe, R., Okawa, Y., Takahashi, S.,
, Y.Regulation of the human CHOP gene promoter by the stressresponse
transcription factor ATF5 via the AARE1 site in humanhepatoma HepG2 cells.Life Sci.87,
294-301 (2010).

Yoshimi, T., Hashimoto, F., Takahashi, S., Takahashi, Y.Suppression of embryonic lung
branching morphogenesis byantisense oligonucleotides against HOM/C homeobox factors.

InVitro Cell Dev.Biol.Anim. 46, 664-672 (2010).

Nakano, H., Miyazawa, T., Kinoshita, K., Yamada, Y., Yoshida, T.Functional screening
identifies a microRNA, miR-491 that inducesapoptosis by targeting Bcl-X(L) in colorectal
cancer cells.Int
.J.Cancer. 127, 1072-1080 (2010).

1432-1, Horinouchi, Hachioji, Tokyo 192-0392 Japan
Laboratory of Environmental Molecular Physiology



 Laboratory of Environmental Molecular Physiology