分子細胞マルチオミクス研究グループ

研究課題

タンパク質の立体構造や細胞内局在、他分子との相互作用等を変化させることで、タンパク質機能を制御しています。タンパク質修飾の生体機能を理解するためには、疾患や生理状態の変化に伴い、どのような修飾機構の変化が生じ、その結果どのようなタンパク質のどの部位にどのような構造の修飾がどの程度発現するのかを、統合的に理解することが重要です。この重要課題に多角的に取り組むための技術開発を進めてきました。近年ではレクチンアレイを全自動化したGlycoBISTを開発し、現在、医療用の診断機器としての実用を目指しています。また、質量分析用データから、タンパク質上の結合糖鎖の情報を網羅的に探索するソフトウェアGrableを開発しました。これらの開発技術により取得したデータを糖鎖科学コミュニティで広く活用できるよう、データベース開発・公開にも積極的に取り組んでいます。

細胞が正常なコントロールから外れて、がんなどの疾患状態になると、糖鎖構造が変化することが知られています。産総研では、疾患における特定のタンパク質上の糖鎖変化を疾患バイオマーカーや創薬標的として活用する研究開発を行い、肝繊維化マーカーM2BPGiなどを開発・上市してきました。しかしながら、変化した糖鎖がどのような機能を持つのかは、ほとんど解明されていません。そこで、正常状態と疾患状態の個体、組織、細胞、分子における糖鎖変化を、臨床試料やモデル動物などを対象として、多様な網羅的解析技術を用いて多角的に解析を行います。マルチオミクス解析（糖鎖、遺伝子、糖タンパク質、タンパク質、分解物など）から得られるデータと、細胞機能（増殖、転移、分化、細胞死など）の病態表現型解析の結果を統合することにより、糖鎖の構造と機能の関係を統合的に理解することを目指しています。

業績リスト

• Miyashita, SI; Ogura, T; Matsuura, SI; Fukuda, E.
  Quantitative Evaluation of Iron-Containing Proteins Bound to Mesoporous Silica Microspheres by Inductively Coupled Plasma Mass Spectrometry and Confocal Laser Raman Microscopy.
  MOLECULES. 2025 Mar 11;30(6):1252. doi:10.3390/molecules30061252
• Takada, N; Ishikawa, M; Sato, K; Kunikata, H; Ninomiya, T; Hanyuda, A; Fukuda, E; Yamaguchi, K; Ono, C; Kirihara, T; Shintani, C; Tsusu, C; Osanai, A; Goshima, N; Izumi, Y; Zorumski, CF; Nakazawa, T.
  Proteome-Wide Analysis of Autoantibodies in Open-Angle Glaucoma in Japanese Population: A Pilot Study.
  BIOMEDICINES. 2025 Mar 14;13(3):718. doi:10.3390/biomedicines13030718
• Boottanun, P; Fuseya, S; Kuno, A.
  Toward spatial glycomics and glycoproteomics: Innovations and applications.
  BBA ADV. 2025 Feb. doi:10.1016/j.bbadva.2025.100146
• Sato, T; Sugiyama, D; Koseki, J; Kojima, Y; Hattori, S; Sone, K; Nishinakamura, H; Ishikawa, T; Ishikawa, Y; Kato, T; Kiyoi, H; Nishikawa, H.
  Sustained inhibition of CSF1R signaling augments antitumor immunity through inhibiting tumor-associated macrophages.
  JCI INSIGHT. 2025 JAN 9. doi:10.1172/jci.insight.178146
• Shimazaki, H; Uojima, H; Yamasaki, K; Obayashi, T;Fuseya, S; Sato, T; Mizokami, M; Kuno, A.
  M2BPgs-HCC: An Automated Multilectin Bead Array Indicating Aberrant Glycosylation Signatures Toward Hepatitis C Virus-Associated Hepatocellular Carcinoma Prognosis.
  MOLECULES. 2024 Nov 28;29(23):5640. doi:10.3390/molecules29235640
• Nagai-Okatani, C; Tomioka, A; Tominaga, D; Sakaue, H; Kuno, A; Kaji, H.
  Inter-tissue glycan heterogeneity: site-specific glycoform analysis of mouse tissue N-glycoproteomes using MS1-based glycopeptide detection method assisted by lectin microarray.
  ANALYTICAL AND BIOANALYTICAL CHEMISTRY. 2024 Dec 16. doi:10.1007/s00216-024-05686-y
• Okamura, Y; Gochi, K; Ishikawa, T; Hayashi, T; Fuseya, S; Suzuki, R; Kanai, M; Inoue, Y; Murakami, Y; Sadaki, S; Jeon, H; Hayama, M; Ishii, H; Tsunakawa, Y; Ochi, H; Sato, S; Hamada, M; Abe, C; Morita, H; Okada, R; Shiba, D; Muratani, M; Shinohara, M; Akiyama, T; Kudo, T; Takahashi, S.
  Impact of microgravity and lunar gravity on murine skeletal and immune systems during space travel.
  SCI REP. 2024 Nov 20;14(1):28774. doi:10.1038/s41598-024-79315-0
• Yamaguchi, Y; Ishii, K; Koizumi, S; Sakaue, H; Maruno, T; Fukuhara, M; Shibuya, R; Tsunaka, Y; Matsushita, A; Bandoh, K; Torisu, T; Murata-Kishimoto, C; Tomioka, A; Mizukado, S; Kaji, H; Kashiwakura, Y; Ohmori, T; Kuno, A; Uchiyama, S.
  Mucin-Type O-Glycosylation in Viral Protein 2 Indirectly Affects the Transduction Efficiency of Recombinant Adeno-Associated Virus Serotype 6.
  MOLECULAR THERAPY. Vol 32 No 4S1, 688-689. 22 APR 2024. doi:
• Sakaue, H; Kuno, A.
  isoAsp-Quest: Workflow development for isoAsp identification using database searches.
  J BIOCHEM. 2024 Oct 23:mvae071. doi: 10.1093/jb/mvae071
• Shimazaki, H; Fuseya, S; Ono, A; Ootani, H; Mizukado, S; Obayashi, T; Tanaka, N; Kajiyama, K; Ashitomi, M; Yamauchi, K; Yasuda, S; Miyabe, T; Nakamura, K; Segawa, O; Kuno, A; Sawakami, K.
  Benchtop glyco-analyzer: from development of biomarker to potential use in clinical setting.
  CLINICAL CHEMISTRY. 2024 Oct 1. doi: 10.1093/clinchem/hvae106.381
• Hayashi, Y; Tajiri, K; Ozawa, T; Angata, K; Sato, T; Togayachi, A; Nagashima, I; Shimizu, H; Murayama, A; Muraishi, N; Narimatsu, H; Yasuda, I.
  Impact of preS1 Evaluation in the Management of Chronic Hepatitis B Virus Infection.
  MEDICINA (Kaunas). 2024 Aug 16;60(8):1334. doi: 10.3390/medicina60081334
• Nagai-Okatani, C; Tominaga, D; Tomioka, A; Sakaue, H; Goda, N; Ko, S; Kuno, A; Kaji, H.
  GRable version 1.0: A software tool for site-specific glycoform analysis with improved MS1-based glycopeptide detection with parallel clustering and confidence evaluation with MS2 information.
  MOL CELL PROTEOMICS. 2024 Aug 22:100833. doi: 10.1016/j.mcpro.2024.100833
• Xu, Z; Zhang, H; Tian, J; Ku, X; Wei, R; Hou, J; Zhang, C; Yang, F; Zou, X; Li, Y; Kaji, H; Tao, SC; Kuno, A; Yan, W; Da, LT; Zhang, Y.
  O-glycosylation of SARS-CoV-2 spike protein by host O-glycosyltransferase strengthens its trimeric structure.
  ACTA BIOCHIM BIOPHYS SIN (Shanghai). 2024 Jul 26. doi: 10.3724/abbs.2024127
• Fuseya, S; Ono, A; Ootani, H; Mizukado, S; Obayashi, T; Tanaka, N; Shimazaki, H; Kajiyama, K; Ashitomi, M; Yasuda, S; Miyabe, T; Nakamura, K; Segawa, O; Sawakami, K; Kuno, A.
  Rapid Glyco-Qualitative Assessment of Recombinant Proteins Using a Fully Automated System.
  J VIS EXP. 2024 Jun 28;(208). doi: 10.3791/66571
• Hayashi, T; Sadaki, S; Tsuji, R; Okada, R; Fuseya, S; Kanai, M; Nakamura, A; Okamura, Y; Muratani, M; Wenchao, G; Sugasawa, T; Mizuno, S; Warabi, E; Kudo, T; Takahashi, S; Fujita, R.
  Dual-specificity phosphatases 13 and 27 as key switches in muscle stem cell transition from proliferation to differentiation.
  STEM CELLS. 2024 Jul 8:sxae045. doi: 10.1093/stmcls/sxae045
• Yamaguchi, Y; Ishii, K; Koizumi, S; Sakaue, H; Maruno, T; Fukuhara, M; Shibuya, R; Tsunaka, Y; Matsushita, A; Bandoh, K; Torisu, T; Murata-Kishimoto, C; Tomioka, A; Mizukado, S; Kaji, H; Kashiwakura, Y; Ohmori, T; Kuno, A;; Uchiyama, S.
  Glycosylation of recombinant adeno-associated virus serotype 6.
  MOL THER METHODS CLIN DEV. 2024 Apr 25;32(2):101256. doi: 10.1016/j.omtm.2024.101256
• Hiono, T; Sakaue, H; Tomioka, A; Kaji, H; Sasaki, M; Orba, Y; Sawa, H; Kuno, A.
  Combinatorial Approach with Mass Spectrometry and Lectin Microarray Dissected Site-Specific Glycostem and Glycoleaf Features of the Virion-Derived Spike Protein of Ancestral and γ Variant SARS-CoV-2 Strains.
  J PROTEOME RES. 2024 Mar 27. doi: 10.1021/acs.jproteome.3c00874
• Miyashita, S; Ogura, T; Matsuura, S; Fukuda, E.
  Particle Size Measurement and Detection of Bound Proteins of Non-Porous/Mesoporous Silica Microspheres by Single-Particle Inductively Coupled Plasma Mass Spectrometry.
  MOLECULES. 2024 Feb 6. 29(5):1086. doi: 10.3390/molecules29051086
• Phuyathip, W; Putthisen, S; Panawan O, Ma-In P; Teeravirote, K; Sintusen, P; Udomkitkosol, S; Detarya, M; Luang. S; Mahalapbutr, P; Sato, T; Kuno, A; Chuangchaiya, S; Silsirivanit, A.
  Role of Wisteria floribunda agglutinin binding glycans in carcinogenesis and metastasis of cholangiocarcinoma.
  HISTOCHEM CELL BIOL. 2024 Feb 23. doi: 10.1007/s00418-024-02270-4
• Matsuda, A; Boottanun, P; Koizumi, S; Nagai, M; Kuno, A.
  Differential Glycoform Analysis of MUC1 Derived from Biological Specimens Using an Antibody-Overlay Lectin Microarray.
  METHODS MOL BIOL. 2024;2763:223-236. doi: 10.1007/978-1-0716-3670-1_19
• Niibori-Nambu, A; Yamasaki, Y; Kobayashi, D; Angata, K; Kuno, A; Panawan, O; Silsilivanit, A; Narimatsu, H; Araki, N.
  Chondroitin sulfate modification of CSPG4 regulates the maintenance and differentiation of glioma initiating cells via integrin-associated signaling.
  J BIOL CHEM. 2024 Feb 1:105706. doi: 10.1016/j.jbc.2024.105706
• Shimazaki, H; Nakamura, K; Ono, A; Segawa, O; Sawakami, K; Koizuka, M; Hirayama, M; Hori, K; Tajima, H; Kuno, A.
  Auto-Lectin Dotcoding by Two Octopuses: Rapid Analysis of Fluorescence-Labeled Glycoproteins by an 8-channel Fully-Automatic Bead Array Scanner with a Rolling-Circle Detector.
  ANAL CHEM. 2023 Aug 3. doi: 10.1021/acs.analchem.3c01395
• Boottanun, P; Nagai-Okatani, C; Nagai, M; Ungkulpasvich, U; Yamane, S; Yamada, M; Kuno, A.
  An improved evanescent fluorescence scanner suitable for high-resolution glycome mapping of formalin-fixed paraffin-embedded tissue sections.
  ANALYTICAL AND BIOANALYTICAL CHEMISTRY. 2023 JUL 3. doi: 10.1007/s00216-023-04824-2
• Tanaka, S; Sakaue, H, Koiwai, T; Okuda, N; Okuyama, K; Horioka, Y; Hiramatsu, Y; Kawashima, M; Ishiguro, N; Sato, T.
  Near-infrared radiation causes sebaceous gland enlargement along with an ROS-dependent augmentation of epidermal growth factor receptor expression in hamsters.
  EXPERIMENTAL DERMATOLOGY. 2023 JUL 4. doi: 10.1111/exd.14878
• Fuseya, S; Izumi, H; Hamano, A; Murakami, Y; Suzuki, R; Koiwai, R; Hayashi, T; Kuno, A, Takahashi, S; Kudo, T.
  Reduction in disialyl-T antigen levels in mice deficient for both St6galnac3 and St6galnac4 results in blood filling of lymph nodes.
  SCI REP. 2023 Jun 29;13(1):10582. doi: 10.1038/s41598-023-37363-y
• Matsuda, KM; Kotani, H; Yamaguchi, K; Okumura, T; Fukuda, E; Kono, M; Hisamoto, T; Kawanabe, R; Norimatsu, Y; Kuzumi, A; Fukayama, M; Fukasawa, T; Ebata, S; Yoshizaki-Ogawa, A; Okamura, T; Shoda, H; Fujio, K; Goshima, N; Sato, S; Yoshizaki, A.
  Significance of anti-transcobalamin receptor antibodies in cutaneous arteritis revealed by proteome-wide autoantibody screening.
  J AUTOIMMUN. 2023 Jan 30;135:102995. doi: 10.1016/j.jaut.2023.102995
• Itakura, Y; Hasegawa, Y; Kikkawa, Y; Murakami, Y; Sugiura, K; Nagai-Okatani, C; Sasaki, N; Umemura, M; Takahashi, Y; Kimura, T; Kuno, A; Ishiwata, T; Toyoda, M.
  Spatiotemporal changes of tissue glycans depending on localization in cardiac aging.
  REGEN THER. 2023 Jan 7;22:68-78. doi: 10.1016/j.reth.2022.12.009
• Zou, X; Lu, J; Deng, Y; Liu, Q; Yan, X; Cui, Y; Xiao, X; Fang, M; Yang, F; Sawaki, H; Sato, T; Tan, B; Lu, X; Feng, B; Kuno, A; Narimatsu, H; Gao, C; Zhang, Y.
  ST6GAL1 inhibits metastasis of hepatocellular carcinoma via modulating sialylation of MCAM on cell surface.
  ONCOGENE. 2022 Dec 17. doi: 10.1038/s41388-022-02571-9
• Tasaki, M; Tateno, H; Sato, T; Narimatsu, H; Saito, K; Nakagawa, Y; Aoki, T; Kamimura, M; Ushiki, T; Takahashi, K; Tomita, Y.
  Hyporesponsiveness against donors ABO antigens of renal grafts after ABO-incompatible kidney transplantation.
  CLIN EXP NEPHROL. 2022 Oct 8. doi: 10.1007/s10157-022-02280-3
• Hiono, T; Kuno, A.
  Glycan Profiling of Viral Glycoproteins with the Lectin Microarray.
  METHODS MOL BIOL. 2022;2556:59-68. doi: 10.1007/978-1-0716-2635-1_6
• Matsuda, KM; Yoshizaki, A; Yamaguchi, K; Fukuda, E; Okumura, T; Ogawa, K; Ono, C; Norimatsu, Y; Kotani, H; Hisamoto, T; Kawanabe, R; Kuzumi, A; Fukasawa, T; Ebata, S; Miyagawa, T; Yoshizaki-Ogawa, A; Goshima, N; Sato, S.
  Autoantibody Landscape Revealed by Wet Protein Array: Sum of Autoantibody Levels Reflects Disease Status.
  FRONT IMMUNOL. 2022 May 4;13:893086. doi: 10.3389/fimmu.2022.893086
• Kuroda, T; Hattori, Y; Kagami, A; Fukuda, E; Tamura, G.
  Genetic modification in the body to make friends with cancer cells?! Dreaming of cancer treatment in 100 years.
  CANCER SCIENCE. 113 1517-1517; FEB
• Fujimoto, M; Arai, E; Nishiyama, N; Maeshima, A; Fujimoto, H; Kitamura, H; Kuno, A; Yoshida, T; Kanai, Y.
  Lectin staining analysis of protein glycosylation in urothelial carcinomas.
  CANCER SCIENCE. 113 378-378; FEB
• Kitazume, Y; Arai, E; Matsuda, A; Kakuda, S; Ohara, K; Maeshima, A; Kuno, A; Yoshida, T; Kanai, Y.
  Alteration of protein glycosylation in renal carcinogenesis.
  CANCER SCIENCE. 113 1284-1284; FEB
• Nagata, Y; Kageyama, S; Ishikawa, T; Kokura, S; Okayama, T; Abe, T; Murakami, M; Otsuka, K; Ariyoshi, T; Kojima, T; Taniguchi, K; Kobayashi, S; Shimada, H; Yajima, S; Suzuki, T; Hirano, S; Tsuchikawa, T; Shichinohe, T; Ueda, S; Kanetaka, K; Yoneda, A; Wada, H; Doki, Y; Yamaue, H; Katsuda, M; Ohi, M; Yasuda, H; Kondo, K; Kataoka, M; Kodera, Y; Koike, M; Shiraishi, T; Miyahara, Y; Goshima,N;Fukuda, E; Yamaguchi, K; Sato, E; Ikeda, H; Yamada, T; Osako, M; Hirai, K; Miyamoto, H; Watanabe, T; Shiku, H.
  Prognostic significance of NY-ESO-1 antigen and PIGR expression in esophageal tumors of CHP-NY-ESO-1-vaccinated patients as adjuvant therapy.
  CANCER IMMUNOL IMMUNOTHER. 2022 Apr 16. doi: 10.1007/s00262-022-03194-5
• Tasaki, M; Tateno, H; Sato, T; Tomioka, A; Kaji, H; Narimatsu, H; Saito, K; Nakagawa, Y; Aoki, T; Kamimura, M; Ushiki, T; Okada, M; Miwa, Y; Hotta, K; Yoshida, Y; Takahashi, K; Tomita, Y.
  A Novel Method of CD31-Combined ABO Carbohydrate Antigen Microarray Predicts Acute Antibody-Mediated Rejection in ABO-Incompatible Kidney Transplantation.
  TRANSPL INT. 2022 Mar 23;35:10248. doi: 10.3389/ti.2022.10248
• Suzuki, R; Nakamura, Y; Koiwai, R; Fuseya, S; Murakami, Y; Hagiwara, K; Sato, T; Takahashi, S; Kudo, T.
  Global Loss of Core 1-Derived O-Glycans in Mice Leads to High Mortality Due to Acute Kidney Failure and Gastric Ulcers.
  INT J MOL SCI. 2022 Jan 24;23(3):1273. doi: 10.3390/ijms23031273
• Sogabe, M; Kojima, S; Kaya, T; Tomioka, A; Kaji, H; Sato, T; Chiba, Y; Shimizu, A; Tanaka, N; Suzuki, N; Hayashi, I; Mikami, M; Togayachi, A; Narimatsu, H.
  Sensitive New Assay System for Serum Wisteria floribunda Agglutinin-Reactive Ceruloplasmin That Distinguishes Ovarian Clear Cell Carcinoma from Endometrioma.
  ANALYTICAL CHEMISTRY; doi:10.1021/acs.analchem.1c04302
• Nagai-Okatani, C; Zou, X; Matsuda, A; Itakura, Y; Toyoda, M; Zhang, Y; Kuno, A.
  Tissue Glycome Mapping: Lectin Microarray-Based Differential Glycomic Analysis of Formalin-Fixed Paraffin-Embedded Tissue Sections.
  METHODS MOL BIOL. 2022;2460:161-180. doi: 10.1007/978-1-0716-2148-6_10
• Angata, K; Wagatsuma, T; Togayachi, A; Sato, T; Sogabe, M; Tajiri, K; Ozawa, T; Nagashima, I; Shimizu, H; Iijima, S; Korenaga, M; Kuno, A; Kaji, H; Mizokami, M; Narimatsu, H.
  O-glycosylated HBsAg peptide can induce specific antibody neutralizing HBV infection.
  BIOCHIM BIOPHYS ACTA GEN SUBJ. 2021 Sep 25:130020. doi: 10.1016/j.bbagen.2021.130020
• Funakoshi, Y; Ohji, G; Yakushijin, K; Ebisawa, K; Arakawa, Y; Saegusa, J; Matsumoto, H; Imanishi, T; Fukuda, E; Matsutani, T; Mori, Y; Iwata, K; Minami, H.
  Massive surge of mRNA expression of clonal B-cell receptor in patients with COVID-19.
  HELIYON. 2021 Aug;7(8):e07748. doi: 10.1016/j.heliyon.2021.e07748. Epub 2021 Aug 10
• Noro, E; Matsuda,A; Kyoutou,T; Sato, T; Tomioka,A; Nagai,M; Sogabe,M; Tsuruno,C; Takahama,Y; Kuno, A; Tanaka,Y; Kaji, H; Narimatsu, H.
  N-glycan structures of Wisteria floribunda agglutinin-positive Mac2 binding protein in the serum of patients with liver fibrosis.
  GLYCOBIOLOGY. 2021 Jun 29:cwab060. doi: 10.1093/glycob/cwab060
• Sakata-Matsuzawa, M; Denda-Nagai, K; Fujihira, H; Noji, M; Ishii-Schrade, KB; Matsuda, A; Kuno, A; Okazaki, M; Nakai, K; Horimoto, Y; Saito, M; Irimura, T
  Glycans unique to the relapse-prone subset within triple-negative breast cancer as revealed by lectin array-based analysis of surgical specimens
  PLoS One. 2021 May 11;16(5):e0250747. doi: 10.1371/journal.pone.0250747. eCollection