Professor

Nishihara Shoko

Profile

Specialized field

Functional biochemistry, cell biology, developmental biology, general medical chemistry, glycobiology, stem cell biology, biochemistry, molecular biology

Research theme

We are conducting research with the aim of clarifying the role of glycans in living organisms. We use various genetic engineering techniques to regulate the expression of glycan-related genes in Drosophila individuals, ES cells, iPS cells, cancer cells, cancer stem cells, human model cells, and organoids to clarify glycan functions. We also create knockout mice for some genes and conduct analysis.

(1) Analysis of glycan-related genes in Drosophila; elucidation of physiological functions of glycans conserved across species
Drosophila is the most advanced model animal in genetics. We focus on the "physiological activity of glycans conserved across biological species" and elucidate the role of glycans in the development of organisms through phenotypic analysis of mutants and knockdowns of glycan-related genes in Drosophila, as well as biochemical and molecular biological analysis. In particular, we are currently analyzing glycosyltransferases required for the maintenance and differentiation of blood stem cells, and glycan structures required for the formation of nerve axons.

(2) Elucidation of glycan functions in human and mammalian pluripotent stem cells (ES cells, iPS cells) and organoids
(1) We will use cultured cells, mainly embryonic stem cells, to examine whether the glycan functions revealed in the previous study are common to humans and other mammals. Specifically, we aim to "elucidate the role of glycans in stem cell maintenance and differentiation" by targeting ES cells and iPS cells. In this project, we first revealed in 2008 that glycans (heparan sulfate) are involved in the maintenance of ES cells. We have further developed this to reveal that the four glycan structures mentioned above are necessary for maintaining the naive pluripotent state. We are currently expanding the scope of our analysis to include various other glycans. There are still not many examples of functional analysis of glycans in embryonic stem cells, and we are playing a pioneering role in this field.

(3) Functional analysis of PAPS transporter knockout mice
PAPS transporters are essential for the sulfation of glycans and proteins, and without them, each molecule cannot be modified by sulfation. We first isolated and identified them in 2003. Currently, we are creating knockout mice and analyzing them. We have found that these mice develop various diseases, and we are currently analyzing the mechanisms of their onset.

(4) Functional analysis of glycan-related genes involved in undiagnosed diseases
Based on the analysis conducted so far, it has been predicted that glycans are involved in many rare undiagnosed diseases, so we have begun analyzing these as well. We will analyze the loss of function of glycan-related genes with mutations that have been found to be associated with diseases using model organisms, stem cell differentiation systems, organoids, etc., to clarify the relationship with diseases.

research content

"Comprehensive elucidation and application of the biological roles of glycans"

During the development of organisms and during the transformation of cells into cancer, the glycan structures on glycoproteins and glycolipids on the cell surface undergo remarkable changes. Translated proteins and lipids are sequentially added with sugars by as many as 200 types of glycosyltransferases in the lumen of the endoplasmic reticulum and Golgi apparatus inside the cell. After undergoing various glycosylation modifications, they are secreted outside the cell in secretory vesicles or presented on the cell membrane. Most proteins on the cell surface are glycoproteins modified with glycosylation. In the transmission of information between cells, it is thought that lectins (proteins that recognize glycans) on the surface of the other cell recognize the presented glycans and transmit information into the cell. For this reason, glycans are deeply involved in various biological phenomena such as development, immunity, infection, and disease.

To know the glycans synthesized, it is important to know what kind of glycosyltransferase is involved in the synthesis. From a comprehensive analysis of glycosyltransferases, we have revealed that in the evolution from yeast to mammals, the basic gene family of glycosyltransferases was created before the divergence of protostomes, including Drosophila, and deuterostomes, which evolved into mammals. Many important glycan structures are thought to be conserved across species. For example, it has been revealed that in certain types of muscular dystrophies, O-Man glycans are abnormal, and the O-Man transferase that synthesizes them is inactivated by mutation in patients with the muscular dystrophies. We have found that Drosophila mutants of this gene cause muscle defects and enhance apoptosis of myoblasts, and have demonstrated that this gene is essential for muscle development. In addition, glycan structures change in cancer cells and stem cells, and glycans are also used as tumor markers and stem cell markers. We were the first in the world to reveal that glycans are involved in the maintenance of embryonic stem cells (ES cells). To date, we have conducted comprehensive analysis and found four types of glycan structures necessary for maintaining the naive pluripotent state: (1) LacdiNAc structure (GalNAcβ1,4GlcNAc), (2) heparan sulfate, (3) O-GlcNAc, and (4) T antigen (Galβ1,3GalNAc), which is a mucin-type O-linked glycan. From such research, it is clear that glycans also play an important role in human ontogeny and disease. Currently, we predict that glycans are involved in many rare undiagnosed diseases, and we are also working on their analysis. The genome sequences of major organisms, including humans, have been determined, and based on that information, comprehensive analysis has progressed to proteome research and even post-translational modification. Glycosylation is a post-translational modification comparable to phosphorylation. We are conducting research with the aim of ``comprehensively elucidating the physiological functions of glycans at the individual level.''

Subjects in charge

Introduction to Cellular Life Science, Introduction to Biofunctional Science, Special Topics in Glycobiology, Data Analysis Seminar, Advanced Research I & II, Special Topics in Cellular Biology, Special Seminars in Life Science I-X, Special Research in Life Science I-X

Main career, work history, and academic background

1953 Born in Tokyo
1982 Ph.D. in Chemistry, Graduate School of Science, The University of Tokyo

Institute of Medicinal Chemistry, Keio University School of Medicine,
Department of Bacteriology II, Jikei University School of Medicine, Tokyo
University of North Carolina at Chapel Hill, Department of Biochemistry,
After working at the Cell Biology Laboratory, Molecular Biology Research Department, Mitsubishi Kasei Life Science Research Institute,

1991 Department of Cell Biology, Institute of Life Science, Soka University Lecturer
1997 Assistant Lecturer Professor, Department of Cell Biology, Institute of Life Science, Soka University
2001 Professor, Department of Cell Biology, Life Science Institute, Soka University
2003 Professor, Department of Bioinformatics, Faculty of Engineering, Soka University
2003 - Present Professor, Department of Bioinformatics, Graduate School of Engineering, Soka University
2015 - Present Faculty of Science and Engineering Department of Science and Engineering for Sustainable Innovation Professor, Soka University
2019 Soka University Faculty of Science and Engineering Center for Glycobiology Systems Director
2020 - Present Soka University Graduate School Graduate School of Science and Engineering Biosciences Major Professor
2021 - Present Soka University Glycan & Life System Integration Center Director

Affiliated academic societies and organizations

Japanese Biochemical Society, Japanese Society for Molecular Biology, Chemical Society of Japan, Japanese Carbohydrate Society, Japanese Cancer Society, Japanese Society for Regenerative Medicine, FCCA (FORUM: CARBOHYDRATES COMING OF AGE), ASBMB (American Society for Biochemistry and Molecular Biology), The Society of Glycobiology, ISSCR (International Society for Stem Cell Research)

Main Papers and Publications

Original Papers
*Corresponding author

  1. Abo, H., Kume, M., Pecori, F., Miura, T., Matsumoto, N., Nishihara, S., Yamamoto, K.:  Disaccharide-tag for highly sensitive identification of O-GlcNAc-modified proteins in mammalian cells.
    PLoS One. 17, e0267804 (2022).
  2. Kobayashi, D., Hiono, T., Ichii, O., Nishihara, S., Takase-Yoden, S., Yamamoto, K., Kawashima, H., Isoda, N., Sakoda, Y.: Turkeys possess diverse Siaα2-3Gal glycans that facilitate their dual susceptibility to avian influenza viruses isolated from ducks and chickens.
    Virus Res. 315, 198771 (2022).
  3. Ogura, C., Nishihara, S.*: Dermatan-4-O-sulfotransferase-1 contributes to the undifferentiated state of mouse embryonic stem cells.
    Front Cell Dev Biol. 9, 733964 (2021).
  4. Pecori, F., Kondo, N., Ogura, C., Miura, T., Kume, M., Minamijima, Y., Yamamoto, K., Nishihara, S.*: Site-specific O-GlcNAcylation of Psme3 maintains mouse stem cell pluripotency by impairing P-body homeostasis.
    Cell Rep. 36, 109361 (2021).
  5. Ichimiya, T., Okamatsu, M., Kinoshita, T., Kobayashi, D., Ichii, O., Yamamoto, N., Sakoda, Y., Kida, H., Kawashima, H., Yamamoto, K., Takase-Yoden, S., Nishihara, S.*:  Sulfated glycans containing NeuAcα2-3Gal facilitate the propagation of human H1N1 influenza A viruses in eggs.
    Virology, 562, 29-39 (2021).
  6. Pecori, F., Yokota, I., Hanamatsu, H., Miura, T., Ogura, C., Ota, H., Furukawa, J.I., Oki, S., Yamamoto, K., Yoshie, O., Nishihara, S.*: A defined glycosylation regulatory network modulates total glycome dynamics during pluripotency state transition.
    Sci Rep. 11, 1276 (2021).
  7. Ogura, C., Hirano, K., Mizumoto, S., Yamada, S., Nishihara, S.*: Dermatan sulphate promotes neuronal differentiation in mouse and human stem cells.
    J Biochem. 169, 55-64 (2021).
  8. Pecori, F., Akimoto, Y., Hanamatsu, H., Furukawa, J.I., Shinohara, Y., Ikehara, Y., Nishihara, S.*: Mucin-type O-glycosylation controls pluripotency in mouse embryonic stem cells via Wnt receptor endocytosis.
    J Cell Sci. 133, jcs245845 (2020).
  9. Miura, T., Yuasa, N., Ota, H., Habu, M., Kawano, M., Nakayama, F., Nishihara, S.*: Highly sulfated hyaluronic acid maintains human induced pluripotent stem cells under feeder-free and bFGF-free conditions.
    Biochem Biophys Res Commun. 518, 506-512 (2019).
  10. Shinchi, H., Nakamura, T., Ota, H., Nishihara, S., Wakao, M., Suda, Y.: Cell profiling based on sugar-chain-cell binding interaction and its application to typing and quality verification of cells.
    Chembiochem. 20, 1810-1816 (2019).
  11. Itoh, K., Akimoto, Y., Kondo. S., Ichimiya, T., Aoki, K., Tiemeyer. M., Nishihara. S.*: Glucuronylated core 1 glycans are required for precise localization of neuromuscular junctions and normal formation of basement membranes on Drosophila muscles.
    Dev Biol. 436, 108-124 (2018).
  12. Miura, T., Kume, M., Kawamura, T., Yamamoto, K., Hamakubo, T., Nishihara, S.*: O-GlcNAc on PKCζ inhibits the FGF4-PKCζ-MEK-ERK1/2 pathway via inhibition of PKCζ phosphorylation in mouse embryonic stem cells.
    Stem Cell Reports, 10, 1–15 (2018).
  13. Miura, T., Fujita, M., Kawano, M., Imadome, K., Yasuda,T., Nishihara, S., Imamura, T., Masuzawa, M., Imai, T., Nakayama, F.: Strong radioprotective FGF1 signaling down-regulates proliferative and metastatic capabilities of the angiosarcoma cell line, ISOS-1, through the dual inhibition of EGFR and VEGFR pathways.
    Clin Transl Radiat Oncol. 7, 83-90 (2017).
  14. Kinoshita, T., Sato, C., Fuwa, T.J., Nishihara, S.*: Short stop mediates axonal compartmentalization of mucin-type core 1 glycans.
    Sci Rep., 7, 41455 (2017).
  15. Miura, T., Nishihara, S.*: O-GlcNAc is required for the survival of primed pluripotent stem cells and their reversion to the naïve state.
    Biochem Biophys Res Commun. 480, 655-661 (2016).
  16. Itoh, K., Akimoto, Y., Fuwa, T.J., Sato, C., Komatsu, A., Nishihara, S.*: Mucin-type core 1 glycans regulate the localization of neuromuscular junctions and establishment of muscle cell architecture in Drosophila.
    Dev Biol., 412, 114-127 (2016).
  17. Miura, T., Hamaguchi, S., Nishihara, S.*: Atmospheric-pressure plasma-irradiationinhibits mouse embryonic stem cell differentiation to mesoderm and endoderm but promotes ectoderm differentiation.
    J. Phys. D: Appl. Phys., 49, 165401-1 - 165401-12 (2016).
  18. Takeuchi, T., Nishiyama, K., Saito, S., Tamura, M., Fuwa, T.J., Nishihara, S., Takahashi, H., Natsugari, H., Arata, Y., Kasai, K.: Preparation of a polyclonal antibody that recognizes a unique galactoseβ1-4fucose disaccharide epitope.
    Carbohydr Res. 412, 50-55 (2015).
  19. Ichimiya, T., Maeda, M., Sakamura, S., Kanazawa, M., Nishihara, S.*, Kimura, Y.*: Identification of β1,3-galactosyltransferases responsible for biosynthesis of insect complex-type N-glycans containing a T-antigen unit in the honeybee.
    Glycoconjugate J., 32, 141-151 (2015).
  20. Yamamoto-Hino, M., Yoshida, H., Ichimiya, T., Sakamura, S., Maeda, M., Kimura, Y., Sasaki, N., Aoki-Kinoshita, K.F., Kinoshita-Toyoda, A., Toyoda, H., Ueda, R., Nishihara, S.*, Goto, S. *: Phenotype-based clustering of glycosylation-related genes by RNAi mediated gene silencing.
    Genes to Cells, 20, 521-542 (2015).
  21. Fuwa, T.J., Kinoshita, T., Nishida, H., Nishihara, S.*: Reduction of T antigen causes loss of hematopoietic progenitors in Drosophila through the inhibition of filopodial extensions from the hematopoietic niche.
    Dev Biol., 401, 206-219 (2015).
  22. Hiono, T., Okamatsu, M., Nishihara, S., Takase-Yoden, S., Sakoda, Y., Kida, H.: A chicken influenza virus recognizes fucosylated α2,3 sialoglycan receptors on the epithelial cells lining upper respiratory tracts of chickens.
    Virology, 456–457, 131–138 (2014).
  23. Miura, T., Ando, A., Hirano, K., Ogura, C., Kanazawa, T., Ikeguchi, M., Seki, A., Nishihara, S., Hamaguchi, S.: Proliferation assay of mouse embryonic stem (ES) cells exposed to atmosphericpressure plasmas at room temperature.
    J. Phys. D: Appl. Phys. 47(44) 445402-1 - 445402-12 (2014).
  24. Hirano, K., Kinoshita, T., Uemura, T., Motohashi, H., Watanabe, Y., Ebihara, T., Nishiyama, H., Sato, M., Suga, M., Maruyama, Y., Tsuji, N.M., Yamamoto, M., Nishihara, S.*, Sato, C.*: Electron microscopy of primary cell cultures in solution and correlative optical microscopy using ASEM.
    Ultramicroscopy,143, 52-66 (2014).
  25. Kinoshita, T., Mori, Y., Hirano, K., Sugimoto, S., Okuda, K., Matsumoto, S., Namiki, T., Ebihara, T., Kawata, M., Nishiyama, H., Sato, M., Suga, M., Higashiyama, K., Sonomoto, K., Mizunoe, Y., Nishihara, S.*, Sato, C. *: Immuno-electron microscopy of primary cell cultures from genetically modified animals in liquid by atmospheric scanning electron microscopy.
    Microsc Microanal, 20, 470-484 (2014).
  26. Ichimiya, T., Nishihara, S., Takase-Yoden, S., Kida, H., Aoki- Kinoshita, K.F.: Frequent glycan structure mining of influenza virus data revealed a sulfated glycan motif that increased viral infection.
    Bioinformatics, 30, 706-711(2014).
  27. Hirano, K., Van Kuppevelt, T.H., Nishihara, S.*: The transition of mouse pluripotent stem cells from the naïve to the primed state requires Fas signaling through 3-O sulfated heparan sulfate structures recognized by the HS4C3 antibody.
    Biochem Biophys Res Commun. 430, 1175–1181 (2013).
  28. Nakayama, F., Umeda, S., Ichimiya, T., Kamiyama, S., Hazawa, M., Yasuda, T., Nishihara, S., Imai, T.: Sulfation of keratan sulfate proteoglycan reduces radiation-induced apoptosis in human Burkitt's lymphoma cell lines.
    FEBS Lett., 587, 231-783 (2013).
  29. Hirano, K., Sasaki, N., Ichimiya, T., Miura, T., Van Kuppevelt,T.H., Nishihara, S.*: 3-O-sulfated heparan sulfate recognized by the antibody HS4C3 contribute to the differentiation of mouse embryonic stem cells via Fas signaling.
    PLoS One, 7, e43440 (2012).
  30. Seki, Y., Mizukura, M., Ichimiya, T., Suda, Y., Nishihara, S., Masuda, M., Takase-Yoden, S.: O-sulfate groups of heparin are critical for inhibition of ecotropic murine leukemia virus infection by heparin.
    Virology, 424, 56-66 (2012).
  31. Sasaki, N., Shinomi, M., Hirano, K., Ui-Tei, K., Nishihara, S.*: LacdiNAc (GalNAcβ1-4GlcNAc) contributes to self-renewal of mouse embryonic stem cells by regulating LIF/STAT3 signaling.
    Stem Cells, 29, 641-650 (2011).
  32. Kamiyama, S., Ichimiya, T., Ikehara, Y., Takase, T., Fujimoto, I., Suda, T., Nakamori, S., Nakamura, M., Nakayama, F., Irimura, T., Nakanishi, H., Watanabe, M., Narimatsu, H., Nishihara, S.*: Expression and role of 3'-phosphoadenosine 5'-phosphosulfate transporters in human colorectal carcinoma.
    Glycobiology, 21, 235-246 (2011).
  33. Yamamoto-Hino, M., Kanie, Y., Awano, W., Aoki-Kinoshita, K.F., Yano, H., Nishihara, S., Okano, H., Ueda, R., Kanie, O., Goto, S.: Identification of genes required for neural-specific glycosylation using functional genomics.
    PLoS Genet., 6, e1001254 (2010).
  34. Sasaki, N., Hirano, T., Kobayashi, K., Toyoda, M., Miyakawa, Y., Okita, H., Kiyokawa, N., Akutsu, H., Umezawa, A., Nishihara, S.*: Chemical inhibition of sulfation accelerates neural differentiation of mouse embryonic stem cells and human induced pluripotent stem cells.
    Biochem Biophys Res Commun. 401, 480-486 (2010).
  35. Ueyama, M., Akimoto, Y., Ichimiya, T., Ueda, R., Kawakami, H., Aigaki, T., Nishihara, S.*: Increased apoptosis of myoblasts in Drosophila model for the Walker-Warburg syndrome.
    PLoS One, 5, e11557 (2010).
  36. Dejima, K., Murata, D., Mizuguchi, S., Nomura, K.H., Izumikawa, T., Kitagawa, H., Gengyo-Ando, K., Yoshina, S., Ichimiya, T., Nishihara, S., Mitani, S., Nomura, K.: Two Golgi-resident 3' -phosphoadenosine 5' -phosphosulfate transporters play distinct roles in heparan sulfate modifications and embryonic and larval development in Caenorhabditis elegans.
    J Biol Chem., 285, 24717-24728 (2010).
  37. Ishikawa, H.O., Ayukawa, T., Nakayama, M., Higashi, S., Kamiyama, S., Nishihara, S., Aoki, K., Ishida, N., Sanai, Y., Matsuno, K.: Two pathways for importing GDP-fucose into the endoplasmic reticulum lumen function redundantly in the O-fucosylation of Notch in Drosophila.
    J Biol Chem., 285, 4122-4129 (2010).
  38. Sasaki, N., Hirano, T., Ichimiya, T., Wakao, M., Hirano, K., Kinoshita-Toyoda, A., Toyoda, H., Suda, Y., Nishihara, S.*: The 3'-phosphoadenosine 5'-phosphosulfate transporters, PAPST1 and 2, contribute to the maintenance and differentiation of mouse embryonic stem cells.
    PLoS One, 4, e8262 (2009).
  39. Dejima, K., Murata, D., Mizuguchi, S., Nomura, K.H. Gengyo-Ando, K., Mitani, S., Kamiyama, S., Nishihara, S., Nomura, K.: The ortholog of human solute carrier family 35 member B1 (UDP-galactose transporter-related protein 1) is involved in maintenance of ER homeostasis and essential for larval development in Caenorhabditis elegans.
    FASEB J., 23, 2215-2225 (2009).
  40. Sesma. J.I., Esther, C.R. Jr, Kreda, S.M., Jones, L., O'Neal, W., Nishihara, S., Nicholas, R.A., Lazarowski, E.R.: ER/Golgi nucleotide sugar transporters contribute to the cellular release of UDP-sugar signaling molecules.
    J. Biol. Chem., 284, 12572-12583 (2009).
  41. Kanie, Y., Yamamoto-Hino, M., Karino, Y., Yokozawa, H., Nishihara, S., Ueda, R., Goto, S., Kanie, O.: Insight into the regulation of glycan synthesis in Drosophila chaoptin based on mass spectrometry.
    PLoS ONE, 4, e5434 (2009).
  42. Yoshida, H., Fuwa, T.J., Arima, M., Hamamoto, H., Sasaki, N., Ichimiya, T., Osawa, K., Ueda, R., Nishihara, S.*: Identification of the Drosophila core 1 β1,3-galactosyltransferase gene that synthesizes T antigen in the embryonic central nervous system and hemocytes.
    Glycobiology, 18, 1094-1104 (2008).
  43. Ono, Y., Kitajima, M., Daikoku, S., Shiroya, T., Nishihara, S., Kanie, Y., Suzuki, K., Goto, S., Kanie, O.: Sequential glycosyltransfer reactions on a microfluidic device: Synthesis of a glycosaminoglycan linkage region tetrasaccharide.
    Lab. on a Chip, 8, 2168-2173 (2008).
  44. Ueyama, M., Takemae, H., Ohmae, Y., Yoshida, H., Toyoda, H., Ueda, R., Nishihara, S.*: Functional analysis of proteoglycan galactosyltransferase II RNAi mutant flies.
    J. Biol. Chem., 283, 6076-6084 (2008).
  45. Sasaki, N., Okishio, K., Ui-Tei, K., Saigo, K., Kinoshita-Toyoda, A., Toyoda, H., Nishimura, T., Suda, Y., Hayasaka, M., Hanaoka, K., Hitoshi, S., Ikenaka, K., Nishihara, S.*: Heparan sulfate regulates self-renewal and pluripotency of embryonic stem cells.
    J. Biol. Chem., 283, 3594-3606 (2008).
  46. Sasaki, N., Yoshida, H., Fuwa, T.J., Kinoshita-Toyoda, A., Toyoda, H., Hirabayashi, Y., Ishida, H., Ueda, R., Nishihara, S.*: Drosophila β1,4-N-acetylgalactosaminyltransferase-A synthesizes the LacdiNAc structures on several glycoproteins and glycosphingolipids.
    Biochem Biophys Res Commun., 354, 522-527 (2007).
  47. Kudo, T., Fujii, T., Ikegami, S., Inokuchi, K., Takayama,Y., Ikehara, Y., Nishihara, S., Togayachi, A., Takahashi, S., Tachibana, K., Yuasa, S., Narimatsu, H.: Mice lacking α1,3-fucosyltransferase IX demonstrate disappearance of Lewis x structure in brain and increased anxiety-like behaviors.
    Glycobiology, 17, 1-9 (2007).
  48. Kusama, S., Ueda, R., Suda, T., Nishihara, S., Etsuko, T.: Involvement of Drosophila Sir2-like genes in the regulation of life span.
    Genes & Genetic Systems, 81, 341-348 (2006).
  49. Goda, E., Kamiyama, S., Uno, T., Yoshida, H., Ueyama, M., Kinoshita-Toyoda, A., Toyoda, H., Ueda, R., Nishihara, S.*: Identification and characterization of a novel Drosophila 3'-phosphoadenosine 5'-phosphosulfate transporter.
    J. Biol. Chem., 281, 28508-28517 (2006).
  50. Kamiyama, S., Sasaki, N., Goda, E., Ui-Tei, K., Saigo, K., Narimatsu, H., Jigami, Y., Kannagi, R., Irimura, T., Nishihara, S.*: Molecular cloning and characterization of a novel 3'-phosphoadenosine 5'-phosphosulfate transporter, PAPST2.
    J. Biol. Chem., 281, 10945-10953 (2006).
  51. Sasaki, N., Manya, H., Okubo, R., Kobayashi, K., Ishidad,H., Toda, T., Endo, T., Nishihara, S.*: β4GalT-II is a key regulator of glycosylation of the proteins involved in neuronal development.
    Biochem Biophys Res Commun., 333, 131-137 (2005).
  52. Ichimiya, T., Manya, H., Ohmae, Y., Yoshida, H., Takahashi, K., Ueda, R., Endo, T., Nishihara, S.*: The twisted abdomen phenotype of Drosophila POMT1 and POMT2 mutants coincides with their heterophilic protein O-mannosyltransferase activity.
    J. Biol. Chem., 279, 42638-42647 (2004).
  53. Kohyama-Koganeya, A., Sasamura, T., Oshima, E., Suzuki, E., Nishihara, S., Ueda, R., Hirabayashi Y.: Drosophila glucosylceramide synthase: A negative regulator of cell death mediated by proapoptotic factors.
    J. Biol. Chem., 279, 35995-6002 (2004).
  54. Suda,T., Kamiyama, S., Suzuki. M., Kikuchi N., Nakayama., Narimatsu H., Jigami , Y., Aoki, T., Nishihara, S.*: Molecular cloning and characterization of a human multi-substrate specific nucleotide-sugar transporter homologous to Drosophila fringe connection.
    J. Biol. Chem., 279, 26469-26474 (2004).
  55. Kudo, T., Kaneko, M., Iwasaki, H., Togayachi, A., Nishihara, S., Abe, K., Narimatsu. H.: Normal embryonic and germ cell development in mice lacking α1,3-fucosyltransferase IX (Fut9) which show disappearance of stage-specific embryonic antigen 1.
    Mol Cell Biol, 24, 4221-4228(2004).
  56. Tanaka, T, Tsuda, C., Miura, T., Inazu, T., Tsuji, S., Nishihara, S., Hisamatsu, M., Kajimoto, T.: Design and synthesis of peptide mimetics of GDP-Fucose: Targeting Inhibitors of fucosyltransferases.
    Synlett, 2004, 243-246 (2004).
  57. Kamiyama, S., Suda, T., Ueda, R., Suzuki, M., Okubo, R., Kikuchi, N., Chiba, Y., Goto, S., Toyoda, H., Saigo, K., Watanabe, M., Narimatsu, H., Jigami, Y., Nishihara, S.*: Molecular cloning and identification of 3'-phosphoadenosine 5'-phosphosulfate transporter.
    J. Biol. Chem., 278, 25958-25963 (2003).

Takemae, H., Ueda, R., Ohkubo, R., Nakato, H., Izumi, S., Saigo, K., Nishihara, S.*: Proteoglycan UDP-galactose: β-xylose β1,4galactosyltransferase I is essential for viability in Drosophila melanogaster.
J. Biol. Chem., 278, 15571-15578 (2003).

Reviews and Publications

  1. Pecori, F., Hanamatsu, H., Furukawa, J.I.*, Nishihara, S.*: Comprehensive and comparative structural glycome analysis in mouse epiblast-like cells.
    Methods Mol Biol. 2490, 179-193 (2022).
  2. Egawa H, Nishihara, S.*: Analysis of 3'-phosphoadenosine 5'-phosphosulfate transporters: Transporter activity assay, real-time reverse transcription polymeraschain reaction, and immunohistochemistry.
    Methods Mol Biol. 2303, 675-685 (2022).
  3. Ota H, Nishihara, S.*: Regulation of 3-O-sulfation of heparan sulfate during transition from the naïve to the primed state in mouse embryonic stem cells.
    Methods Mol Biol. 2303, 443-452 (2022).
  4. Itoh K, Nishihara, S.*: Mucin-type O-glycosylation in the Drosophila nervous system.
    Front Neuroanat. 15, 767126 (2021) .
  5. Pecori, F., Nishihara, S.*: Transient induction and characterization of mouse epiblast-like cells from mouse embryonic stem cells.
    Methods Mol Biol. 2021 May 5. doi: 10.1007/7651_2021_403. Online ahead of print.
  6. Itoh, K., Nishihara, S.*: Drosophila melanogaster in glycobiology: Their mutants are excellent models for human diseases. Comprehensive Glycoscience, 2nd edition. Barchi Jr., Joseph (ed.). Oxford: Elsevier, vol.5, 1-35 (2021).
  7. Nishihara, S.*: From structure and function of glycans in stem cells to application in regenerative medicine.
    Glycoforum. 2020 Vol.24 (4), A9 DOI: https://doi.org/10.32285/glycoforum.24A9 Aug 01, 2021.
  8. Nishihara, S.*: Functional analysis of glycosylation using Drosophila melanogaster.
    Glycoconj J. 37, 1-14 (2020).
  9. Nishihara, Sachiko*: Glycans that control stem cells.
    Biochemistry, Journal of Japanese Biochemical Society, 92, 94-106 (2020).
  10. Nishihara, S.*: Drosophila melanogaster.
    Glycoscience: Basic Science to Applications. Insights from the Japan Consortium for Glycobiology and Glycotechnology (JCGG). Taniguchi, N. (ed.). Springer, Chapter 4, 4-7, 100-101(2019)
  11. Nishihara, S.*: Roles of glycans in development, evolution and stem cells.
    Glycoscience: Basic Science to Applications. Insights from the Japan Consortium for Glycobiology and Glycotechnology (JCGG). Taniguchi, N. (ed.). Springer, Chapter 11, 11-1, 191-193 (2019).
  12. Nishihara, S.*: Posttranscriptional regulation of glycan expression by microRNA.
    Glycoscience: Basic Science to Applications. Insights from the Japan Consortium for Glycobiology and Glycotechnology (JCGG). Taniguchi, N. (ed.), Springer, Chapter 11, 11-5, 200-201 (2019).
  13. Nishihara, S.*: Influenza drug formulation.
    Glycoscience: Basic Science to Applications. Insights from the Japan Consortium for Glycobiology and Glycotechnology (JCGG). Taniguchi, N. (ed.), Springer, Chapter 14, Box 14.1, 232 (2019).
  14. Taichi Miura, Shoko Nishihara*: Function of O-GlcNAc in pluripotent stem cells.
    TIGG, 31, E69–E75 (2019).
  15. Nishihara, S.*: Glycans in stem cell regulation: from Drosophila tissue stem cells to mammalian pluripotent stem cells.
    FEBS Letters, 592, 3773-3790 (2018).
  16. Nishihara, S.*, Hamaguchi, S.: Molecular dissection of biological effects for mouse embryonic stem cells differentiation treated by low-temperature atmospheric-pressure plasma (APP).
    Plasma Medical Science. 1st ed. Hori, M. (eds). Academic Press, Chapter 6.6, 353-359 (2018).
  17. Kinoshita, T., Itoh, K., Nishihara, S.*: Functions of mucin-type O-glycans in the nervous system.
    TIGG, 30, E103-E108 (2018).
  18. Nishihara, Sachiko*, Ito, Kazuyoshi: The role of glycans in stem cells - from Drosophila models to ES cells - Glycans functioning in stem cells.
    Chemistry and Biology, 55, 750-758 (2017).
  19. Sato, C., Kinoshita, T., Memtily, N., Sato, M., Nishihara, S., Yamazawa, T., Sugimoto, S.: Correlative light-electcron micoscopy in liquids using an inverted SEM.
    Methods in Cell Biology, 140, 187-213 (2017).
  20. Nishihara, Sachiko*: Functions of glycans in pluripotent stem cells: glycans involved in naive and primed states.
    Bio Clinica, 32, 412-418 (2017) New developments in glycobiology, edited by Hidetomo Miyoshi
  21. Nishihara, S.*, Ota, H., Miura T.: Atmospheric pressure plasma irradiation on embryonic stem cells: Signals and differentiation.
    Plasma Medicine, 7, 215–225 (2017).
  22. Nishihara, S.*: Glycans define the stemness of naïve and primed pluripotent stem cells.
    Glycoconj J., 34, 737-747(2017).
  23. Hisashi Fuwa and Sachiko Nishihara*: Glycan-mediated control of development and signal transduction revealed by Drosophila.
    Handbook of New Glycan Function Development and Application– From Drug Discovery and Medical Treatment to Food Development – , edited by Kazunari Akiyoshi, NTS, Chapter 5, Section 1, pp. 226-229 (2015) .
  24. Nishihara, S.*: Glycan functions and signals in embryonic stem cells.
    Glycoscience: Biology and Medicine, edited by Taniguchi N et al., Springer, 2, Part IX, Chapter 180, 1465-1473 (2015).
  25. Nishihara, S.*: Members of the nucleotide-sugar transporter family and their functions.
    Glycoscience: Biology and Medicine, edited by Taniguchi N et al., Springer, 2, Part X, Chapter 154, 1253-1266 (2015).
  26. Fuwa, T.J., Nishihara, S.*: Functional analysis of glycans using Drosophila mutants and RNAi.
    Glycoscience: Biology and Medicine, edited by Taniguchi N et al., Springer, 2, Part IX, Chapter 107, 891-900 (2015).
  27. Nishihara, S.*: Adenosine 3′-phospho 5′-phosphosulfate transporter 1,2 (PAPST1,2) (SLC35B2,3).
    Handbook of Glycosyltransferases and Related Genes (2nd edition), edited by Taniguchi N., Springer, 3, Section XIV, Chapter 122, 1379-1392 (2014).
  28. Nishihara, S.*: UDP-N-acetylglucosamine/UDP-glucose/GDP-mannose transporter (HFRC1) (SLC35D2).
    Handbook of Glycosyltransferases and Related Genes (2nd edition), edited by Taniguchi N., Springer, 3, Section XIV, Chapter 125, 1413-1422 (2014).
  29. Nishihara, S.*: CMP-sialic acid transporter (CST)(SLC35A1).
    Handbook of Glycosyltransferases and Related Genes (2nd edition) edited by Taniguchi N., Springer, 3, Section XIV, Chapter 121, 1369-1378 (2014).
  30. Nishihara, S.*: Self-renewal of naïve state mouse embryonic stem cells: role of LacdiNAc in LIF/STAT signaling.
    Stem cells and cancer stem cells, Therapeutic applications in disease and injury, edited by Hayat M. A., Springer, 11, Part 1, Chapter 4, 41-50 (2014).
  31. Nishihara, Sachiko*: Glycan structures and functional mechanisms involved in the maintenance of undifferentiated state and differentiation of pluripotent stem cells
    Experimental Medicine, 31, 574-1582 (2013).
  32. Nishihara, S.*: Accelerated neural differentiation of human induced pluripotent stem cells using chlorate treatment.
    Stem cells and cancer stem cells, Therapeutic applications in disease and injury edited by Hayat M. A., Springer, 7, Part 4, Chapter 24, 249-257 (2012).
  33. Sasaki, N., Nishihara, S.*: Gene silencing in mouse embryonic stem cells.
    Methods Mol. Biol., Proteoglycans edited by Françoise R, Springer, 836, Part I, Chapter 4, 53-61(2012).
  34. Norihiko Sasaki, Sachiko Nishihara*: Significance of glycan expression in pluripotent stem cells.
    Medical Progress, 239, 1277-1282 (2011).
  35. Nishihara, S.*: The function of glycan structures for the maintenance and differentiation of embryonic stem cells.
    Embryonic Stem Cells: The hormonal regulation of pluripotency and embryogenesis, edited by Craig S. Atowood, INTECH, Part 1, Chapter 6, 101-124 (2011).
  36. Nishihara, S.*: Glycosyltransferases and transporters that contribute to proteoglycan synthesis in Drosophila: Identification and functional analyses using the heritable and inducible RNAi system.
    Method in Enzymnology, 480, 323-351 (2010).
  37. Nishihara, S.*: The function of glycan structures expressed on embryonic stem cells.
    TIGG, 21, 207-218 (2009).
  38. Nishihara, Sachiko*: Drosophila RNAi system.
    The lung perspective, 17, 202-205 (2009).
  39. Nishihara, Sachiko*: Role of glycans elucidated by Drosophila.
    The third chain of life: The mystery of glycans is now solved. Edited by Koichi Furukawa, Chapter E, 138-144 (2009).
  40. Nishihara, Sachiko*: Sulfated glycans involved in maintaining the undifferentiated and pluripotent state of ES cells.
    Chemical Industry, 59, 947-954 (2008).
  41. Shin Kamiyama, Shoko Nishihara*: Regulation of glycan synthesis by nucleotide sugar transporters and PAPS transporters.
    Protein Nucleic Acid Enzyme, 53, 1486-1494 (2008).
  42. Nishihara, S.*: Nucleotide sugar transporter genes and their functional analysis.
    Experimental Glycoscience - Glycobiology, edited by Taniguchi et al., Springer, Part1, Section III, 103-107 (2008).
  43. Nishihara, S.*: Functional analysis of sugar chains using a genome-wide RNAi system in Drosophila.
    Experimental Glycoscience - Glycobiology, edited by Taniguchi et al., Springer, Part2, Section XIV, 285-89 (2008).
  44. Nishihara, S.*: Drosophila development, RNAi, and glycobiology.
    Comprehensive Glycoscience - From Chemistry to Systems Biology, edited by Johannis P Kamerling et al., Elsevier, section E. Cell Glycobiology and Development, 4.05, 49-79 (2007).
  45. Nishihara, Sachiko*: Genome-wide analysis of glycan functions using the Drosophila RNAi system.
    Glycoscience for the Future, edited by K. Nagai, Chapter 4, Section 9-1, 323-325 (2005).
  46. Nishihara, Sachiko*: Identification and functional analysis of sugar nucleotide transporter genes.
    Glycoscience for the Future, edited by Katsutaka Nagai, Chapter 3, Section 3, 191-193 (2005).
  47. Morio Kamiyama, Sachiko Nishihara*: Glycosylation and development of Drosophila.
    New developments in glycoscience, edited by Naoyuki Taniguchi and Yukinari Ito, Chapter 12, Section 2, 318-324 (2005) .
  48. Hideki Yoshida, Sachiko Nishihara*: Role of glycans in Drosophila neurogenesis.
    Protein Nucleic Acid Fermentation, 49, 2319-2326 (2004).
  49. Nishihara Sachiko*: RNAi .
    Biology for studying medicine, edited by Naoyuki Taniguchi and Yoshihiro Yoneda, Chapter 6, Section E, 444-451 (2004) .
  50. Nishihara, S.*, Ueda, R., Goto, S., Toyoda, H., Ishida, H., Nakamura, M.: Approach for functional analysis of glycan using RNA interference.
    Glycoconj J., 21, 63-68 (2004).
  51. Kamiyama, S., Nishihara, S.*: The subcellular PAPS synthesis pathway responsible for the sulfation of proteoglycans: a comparison between humans and Drosophila melanogaster.
    TIGG, 16, 109-123 (2004).
  52. Nishihara, Sachiko*: Drosophila glycome: an approach to functional analysis using fruit flies.
    J. Electrophoresis, 48, 19-25 (2004).
  53. Nishihara, Sachiko*, Ueda, Ryu: Analysis of glycan functions using RNAi system.
    Chemical Industry, 54, 760-765 (2003).
  54. Nishihara, S.*, Ueda, R.: Glycobiology of Drosophila.
    Protein Nucleic Acid Enzyme, 48, 1064-1071 (2003).
Specialized field

Functional biochemistry, cell biology, developmental biology, general medical chemistry, glycobiology, stem cell biology, biochemistry, molecular biology

Research theme

We are conducting research with the aim of clarifying the role of glycans in living organisms. We use various genetic engineering techniques to regulate the expression of glycan-related genes in Drosophila individuals, ES cells, iPS cells, cancer cells, cancer stem cells, human model cells, and organoids to clarify glycan functions. We also create knockout mice for some genes and conduct analysis.

(1) Analysis of glycan-related genes in Drosophila; elucidation of physiological functions of glycans conserved across species
Drosophila is the most advanced model animal in genetics. We focus on the "physiological activity of glycans conserved across biological species" and elucidate the role of glycans in the development of organisms through phenotypic analysis of mutants and knockdowns of glycan-related genes in Drosophila, as well as biochemical and molecular biological analysis. In particular, we are currently analyzing glycosyltransferases required for the maintenance and differentiation of blood stem cells, and glycan structures required for the formation of nerve axons.

(2) Elucidation of glycan functions in human and mammalian pluripotent stem cells (ES cells, iPS cells) and organoids
(1) We will use cultured cells, mainly embryonic stem cells, to examine whether the glycan functions revealed in the previous study are common to humans and other mammals. Specifically, we aim to "elucidate the role of glycans in stem cell maintenance and differentiation" by targeting ES cells and iPS cells. In this project, we first revealed in 2008 that glycans (heparan sulfate) are involved in the maintenance of ES cells. We have further developed this to reveal that the four glycan structures mentioned above are necessary for maintaining the naive pluripotent state. We are currently expanding the scope of our analysis to include various other glycans. There are still not many examples of functional analysis of glycans in embryonic stem cells, and we are playing a pioneering role in this field.

(3) Functional analysis of PAPS transporter knockout mice
PAPS transporters are essential for the sulfation of glycans and proteins, and without them, each molecule cannot be modified by sulfation. We first isolated and identified them in 2003. Currently, we are creating knockout mice and analyzing them. We have found that these mice develop various diseases, and we are currently analyzing the mechanisms of their onset.

(4) Functional analysis of glycan-related genes involved in undiagnosed diseases
Based on the analysis conducted so far, it has been predicted that glycans are involved in many rare undiagnosed diseases, so we have begun analyzing these as well. We will analyze the loss of function of glycan-related genes with mutations that have been found to be associated with diseases using model organisms, stem cell differentiation systems, organoids, etc., to clarify the relationship with diseases.