Kyushu University Academic Staff Educational and Research Activities Database
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Shigeki Furuya Last modified date:2020.02.06

Professor / Division of Systems Bioengineering
Department of Bioscience and Biotechnology
Faculty of Agriculture

Graduate School
Undergraduate School
Other Organization

Academic Degree
Field of Specialization
Molecular Neurobiology, Nutritional Genomics, Systems Biology
Outline Activities
Our laboratory is interested in understanding molecular and cellular mechanisms that regulate responses to limited availability of simple nutrients amino acids in animals. Over the last several years, we have focused in particular on the physiological role of serine biosynthesis in the development and function of brain. We have used targeted gene disruption approach to create mouse models of human serine deficiency disorder, which exhibits severe neurological symptoms in patients. Current projects being undertaken are:

1) Functional genomics analysis of knockout mice lacking serine biosynthesis.
2) Development of an integrative omics platform for analysis of mouse models of human serine deficiency disorder.
3) Characterization of the mechanisms underlying growth retarded phenotypes exhibited by mice lacking serine biosynthesis.
4) Development of in vivo bioassay system for screening food components enhancing brain function.
Research Interests
  • Regulation of brain metabolism and function by food proteins/peptides
    keyword : Food functionality, Food protein/peptide, brain metabolism and function
  • Functional genomics analysis of nutrient-gene interaction using knockout mice lacking amino acid biosynthesis
    keyword : nutrient-gene interaction, amino acids, knockout mouse, omics, brain development and function, omics, systems biology
Academic Activities
1. An Essential Role for Endogenous L-Serine Biosynthesis in Brain Development and Function..
1. Yui Kawano, Hu Yating, Masahiro Sasaki, Shigeki Furuya, Silk sericin intake leads to increases in L-serine and L-tyrosine levels in the mouse brain and the simultaneous facilitation of brain noradrenergic turnover, Bioscience, Biotechnology and Biochemistry, 10.1080/09168451.2019.1676693, 84, 2, 372-379, 2020.02, Sericin is a protein component of the silkworm cocoon, and contains a high proportion of L-serine, but it has been mostly disposed of as an industrial waste. However, recent studies have revealed its unique biological functionalities beneficial to human health. This study aimed to evaluate the effect of acute oral intake of sericin on amino acid and neurotransmitter metabolism in the mouse brain. Acute administration of chemically modified sericin (0.26 g/30 g body weight) increased L-serine and L-tyrosine levels in the serum and brain, although the L-tyrosine content in the sericin was less than 3% (w/w). In addition, sericin administration led to a significant facilitation of noradrenergic turnover via enhancement of 3-methoxy-4-hydroxyphenylethyleneglycol, a principal metabolite of noradrenaline, in several of the brain regions examined. These present findings suggest that oral intake of sericin efficiently delivers L-serine and L-tyrosine to the brain, thus stimulating noradrenergic activity in the brain..
2. Mohammad R. Haque, Aiko Hirowatari, Ayumi Koyanagi, Takashi Ichinose, Maiko Abiru, Shinya Mohri, Shigeki Furuya, Kohji Yamamoto, Molecular characterization and expression analysis of a phosphoserine aminotransferase involving L-serine synthesis from silkworm, Bombyx mori, Archives of insect biochemistry and physiology, 10.1002/arch.21553, 101, 2, 2019.06, In this study, we identified and characterized a phosphoserine aminotransferase (bmPSAT) from Bombyx mori (B. mori) that is responsible for L-serine biosynthesis. A complementary DNA that encodes bmPSAT was cloned by reverse transcriptase polymerase reaction and sequenced. The presumed amino acid sequence revealed 47–87% identity with known PSATs from insects, humans, plants, and bacteria. Through phylogenetic analysis, we found that bmPSAT is evolutionary related to insect PSATs. Recombinant bmPSAT was produced in Escherichia coli by using a cold-shock promoter and purified to homogeneity. This enzyme utilizes phosphohydroxypyruvate and glutamate for transamination. bmPSAT messenger RNA (mRNA) was expressed at higher levels in several tissues of standard strain silkworm including the silk gland, whereas a sericin-deficient silkworm strain exhibited a diminished expression of bmPSAT mRNA in the silk gland. These findings indicate that bmPSAT may play an important role in synthesizing and supplying L-serine in the larva of B. mori..
3. Yukako Hino, Ayumi Koyanagi, Motohiro Maebuchi, Takashi Ichinose, Shigeki Furuya, Comparison of the effect of soy and casein-derived peptide administration on tyrosine and catecholamine metabolism in the mouse brain., J. Nutr. Sci. Vitaminol. (Tokyo),, 64, 5, 329-334, 2018.11, [URL].
4. Saar Vandekeere, Charlotte Dubois, Joanna Kalucka, Mark R. Sullivan, Melissa García-Caballero, Jermaine Goveia, Rongyuan Chen, Frances F. Diehl, Libat Bar-Lev, Joris Souffreau, Andreas Pircher, Saran Kumar, Stefan Vinckier, Yoshio Hirabayashi, Shigeki Furuya, Luc Schoonjans, Guy Eelen, Bart Ghesquière, Eli Keshet, Xuri Li, Matthew G.Vander Heiden, Mieke Dewerchin, Peter Carmeliet, Serine Synthesis via PHGDH Is Essential for Heme Production in Endothelial Cells., Cell Metabolism,, 28, 4, 573-587, .e13, 2018.07, [URL], The role of phosphoglycerate dehydrogenase (PHGDH), a key enzyme of the serine synthesis pathway (SSP), in endothelial cells (ECs) remains poorly characterized. We report that mouse neonates with EC-specific PHGDH deficiency suffer lethal vascular defects within days of gene inactivation, due to reduced EC proliferation and survival. In addition to nucleotide synthesis impairment, PHGDH knockdown (PHGDHKD) caused oxidative stress, due not only to decreased glutathione and NADPH synthesis but also to mitochondrial dysfunction. Electron transport chain (ETC) enzyme activities were compromised upon PHGDHKD because of insufficient heme production due to cellular serine depletion, not observed in other cell types. As a result of heme depletion, elevated reactive oxygen species levels caused EC demise. Supplementation of hemin in PHGDHKD ECs restored ETC function and rescued the apoptosis and angiogenesis defects. These data argue that ECs die upon PHGDH inhibition, even without external serine deprivation, illustrating an unusual importance of serine synthesis for ECs..
5. Momoko Hamano, Yurina Haraguchi, Tomoko Sayano, Chong Zyao, Yashiho Arimoto, Yui Kawano, Kazuki Moriyasu, Miyako Udono, Yoshinori Katakura, Takuya Ogawa, Hisanori Kato, Shigeki Furuya, Enhanced vulnerability to oxidative stress and induction of inflammatory gene expression in 3-phosphoglycerate dehydrogenase-deficient fibroblasts., FEBS Open Bio, 10.1002/2211-5463.12429, 2018.04.
6. Tomoko Sayano, Yuki Kawano, Wataru Kusada, Yashiho Arimoto, Kayoko Esaki, Momoko Hamano, Miyako Udono, Yoshinori Katakura, Takuya Ogawa, Hisanori Kato, Yoshio Hirabayashi, Shigeki Furuya, Adaptive response to L-serine deficiency is mediated by p38 MAPK activation via 1-deoxysphinganine in normal fibroblasts., FEBS Open Bio, DOI: 10.1002/2211-5463.12038, 2016.03, [URL].
7. Kayoko Esaki, Tomoko Sayano, Chiaki Sonoda, Takumi Akagi, Takeshi Suzuki, Takuya Ogawa, Masahiro Okamoto, Takeo Yoshikawa, Yoshio Hirabayashi, Shigeki Furuya, L-Serine deficiency elicits intracellular accumulation of cytotoxic deoxysphingolipids and lipid body formation. , J. Biol. Chem., 10.1074/jbc.M114.603860, 290, 23, 14595-14609, 2015.06, [URL].
8. Takashi Ichinose, Kazuki Moriyasu, Akane Nakahata, Mitsuru Tanaka, Toshiro Matsui, Shigeki Furuya, Orally administrated dipeptide Ser-Tyr efficiently stimulates noradrenergic turnover in the mouse brain., Biosci. Biotech. Biochem., doi: 10.1080/09168451.2015.1044932, 2015.05.
9. Jeffrey T. Ehmsen, Ting Martin Ma, Hagit Sason, Dina Rosenberg, Tadashi Ogo, Shigeki Furuya, Solomon H. Snyder, Herman Wolosker, D-Serine in glia and neurons derives from 3-phosphoglycerate dehydrogenase., J. Neurosci. , doi: 10.1523/​JNEUROSCI.4914-12.2013, 33, 12464-12469, 2013.07.
10. Kayoko Esaki, Taketo Ohmori, Motohiro Maebuchi, Toshihiro Nakamori, Toshihisa Ohshima, Shigeki Furuya, Increased tyrosine in the brain and serum of mice by orally administering dipeptide SY. , Biosci. Biotech. Biochem. , 77, 847-849, 2013.04.
11. Tomoko Sayano, Yuriko Kawakami, Wataru Kusada, Takeshi Suzuki, Yuki Kawano, Akihiro Watanabe, Kana Takashima, Yashiho Arimoto, Kayoko Esaki, Akira Wada, Fumiaki Yoshizawa, Masahiko Watanabe, Masahiro Okamoto, Yoshio Hirabayashi, Shigeki Furuya, Serine deficiency caused by genetic Phgdh deletion leads to robust induction of 4E-BP1 and subsequent repression of translation initiation in the central nervous system., FEBS J., doi: 10.1111/febs.12146., 280, 1502-1517, 2013.02.
12. Yang, JH., Wada, A., Yoshida, K., Miyoshi, Y., Sayano, T., Esaki, K., Kinoshita, O.M., Tomonaga, S., Azuma, N., Watanabe, M., Hamase, K., Zaitsu, K., Machida, T., Messing, A., Itohara, S., Hirabayashi, Y., Furuya, S.  , Brain-specific Phgdh deletion reveals a pivotal role for L-serine biosynthesis in controlling the level of D-serine, an NMDA receptor co-agonist, in adult brain., J. Biol. Chem., 285, 41380-41390, 2010.12.
13. Kinoshita, O.M., Furuya, S., Ito, S., Shinoda, Y., Yamazaki, Y., Greimel, P., Ito, Y., Hashikawa, T., Machida, T., Nagatsuka, Y., Hirabayashi, Y. , Lipid rafts enriched in phosphatidylglucoside direct astroglial differentiation by regulating tyrosine kinase activity of EGF receptors., Biochem. J. , 419, 565-575, 2009.05.
14. Kawakami, Y., Yoshida, K., Yang, J.H., Suzuki, T., Azuma, N., Tanaka, H., Watanabe, M., Kuhara, S., Hirabayashi, Y., Furuya, S. , Impaired neurogenesis in the embryonic spinal cord of Phgdh knockout mouse, a serine deficiency disorder model. , Neurosci. Res., 63, 184-193, 2009.03.
15. Kinoshita, O.M., Shinoda, Y., Sakai, K., Hashikawa, T., Watanabe, M., Machida, T., Hirabayashi, Y., Furuya, S. , Selective up-regulation of 3-phosphoglycerate dehydrogenase (Phgdh) expression in adult subventricular zone neurogenic niche., Neurosci. Lett. , 453, 21-26., 2009.03.
16. Hirabayashi, Y., Furuya, S. , Roles of L-serine and sphingolipid synthesis in brain development and neuronal survival., Prog. Lipid Res, 47, 3, 188-203., 2008.02.
17. Furuya, S., Yoshida, K., Kawakami,Y., Yang, J-H., Sayano, T., Azuma, N., Tanaka, H., Kuhara, S., Hirabayashi, Y. , Inactivation of the 3-phosphoglycerate dehydrogenase gene in mice: Changes in gene expression and associated regulatory networks resulting from serine deficiency. , Funct. Integr. Genomics. , 8, 235-249, 2008.07.
18. Yoshida, K., Furuya, S., Osuka, S., Mitoma, J., Shinoda, Y., Watanabe, M., Azuma, N., Tanaka, H., Hashikawa, T., Itohara, S., and Hirabayashi, Y., Targeted disruption of the mouse 3-phosphoglycerate dehydrogenase gene causes severe neurodevelopmental defects and results in embryonic lethality., J. Biol. Chem., 279, 3573-3577, 2004.04.
19. Shimizu, M., Furuya, S., Shinoda, Y., Mitoma, J., Okamura, T., Miyoshi, I., Kasai, N., Hirabayashi, Y., Suzuki, Y., Functional analysis of mouse 3-phosphoglycerate dehydrogenase (Phgdh) gene promoter in developing brain., J. Neurosci. Res., 76, 623-632, 2004.06.
20. Mitoma, J., Furuya, S., Shimizu, M., Shinoda, Y., Yoshida, K., Azuma, N., Tanaka, H., Suzuki, Y., Hirabayashi, Y., Mouse 3-phosphoglycerate dehydrogenase gene: Genomic organization, chromosomal localization, and promoter analysis., Gene, 334, 15-22, 2004.05.
21. Furuya, S. and Watanabe, M., Novel neuroglial and glioglial relationships mediated by L-serine metabolism., Arch. Histol. Cytol., 66, 109-121, 2003.11.
22. Chen, P., Peng, C., Luff, J., Spring, K., Watters, D., Bottle, S., Fururya, S. and Lavin, M.F., Oxidative stress is responsible for deficient survival and dendritogenesis in Purkinje neurons from Atm mutant mice., J. Neurosci., 23, 11453-11460, 2003.12.
1. 古屋 茂樹, Serine Biosynthesis Disorder, 2nd Asia Pacific Course: Paediatric Neurometabolic and Movement Disorders, Recordati Rare Diseases Foundation, 2016.06.
2. Altered Gene Expression in Adult Brain of Serine Deficiency Model Mouse. .
3. L-Serine revisited: What have mouse knockout model and human serine deficiency disorder taught us about L-Serine? Shigeki Furuya, 
ICoFF2007 - International Conference on Food Factors for Health Promotion, Symposium 06: Functions of Amino Acids as Non-Nutrients.
November 29th, 2007, Kyoto, Japan.
4. Generation and characterization of Phgdh knockout Mouse: A Serine Deficiency Model. Shigeki FUruya, 10th Asian Congress of Nutrition (ACN 2007), Symposium (S18): New Frontier of Amino Acid Science, September 11th, 2007, Taipei, Taiwan.
5. Gene Expression Profiling of Phgdh Knockout Mouse, A Serine Deficiency Model. Shigeki Furuya, 10th Asian Congress of Nutrition (ACN 2007), September 11th, 2007, Taipei.
6. 古屋 茂樹, Serine Biosynthesis is a Metabolic Element Necessary for Neural Progenitor Functions, Neuroscience 2005 第28回日本神経科学会シンポジウム「成体脳で起こる神経新生:分子基盤と機能的意義」, 2005.07.
Membership in Academic Society
  • Japanese Society of Nutrition and Food Science
  • Japanese Society for Amino Acid Sciences
  • Japan Society for Bioscience, Biotechnology, and Agrochemistry
  • The Japan Neuroscience Society
Educational Activities
Graduate School: Overview of Metabolic Regulation Research