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大瀧　みちる (オオタキ　ミチル)

先端生命科学研究院　先端融合科学研究部門　新薬探索研究分野特任助教

研究者基本情報

■ 学位
  • 博士（環境科学）, 北海道大学, 2016年09月
■ URL
researchmap URLホームページURL■ ID 各種
研究者番号
  • 10978703
ORCID IDJ-Global ID

研究活動情報

■ 論文
  • Nanosomal Irinotecan Targeting Pancreatic Cancer Cell Surface Neuraminidase-1 Sialidase.
    Ken Murakami; Yasuhiro Yokoi; Nozomi Hirane; Michiru Otaki; Shin-Ichiro Nishimura
    Advanced healthcare materials, 14, 28, e01673, 2025年11月, ［国際誌］
    英語, 研究論文（学術雑誌）
  • Site-Specific O-Glycosylation in Oncofetal Fibronectin IIICS Domain Creates Cancer Stage-Specific Biomarkers.
    Nozomi Hirane; Yasuhiro Yokoi; Aiko Kobayashi; Misaki Yamada; Taiki Konno; Hiroyuki Kumeta; Hajime Wakui; Michiru Otaki; Yoshiaki Miura; Tatsuhiko Kakisaka; Toshiya Kamiyama; Akinobu Taketomi; Kazuhiro Nouso; Satoshi Kimura; Shin-Ichiro Nishimura
    Journal of the American Chemical Society, 147, 14, 12170, 12184, 2025年04月09日, ［国際誌］
    英語, 研究論文（学術雑誌）, Despite the pathological importance of oncofetal fibronectin isoforms associated with cancer cell progression and metastasis, our understanding of the structural and molecular details that occurred in this abundant and ubiquitous extracellular matrix component remains largely unknown. Here, we communicate that site-specific O-glycosylation in the oncofetal fibronectin creates cancer stage-specific serum biomarkers for hepatocellular carcinoma (HCC) by quantitative MS-based glycoproteomic approach. Selective reaction monitoring (SRM) using a structure-defined synthetic glycopeptide library enabled absolute quantitation of the targeted label-free tryptic fragments bearing cancer-relevant O-glycans derived from the type III homology connective segment (IIICS) domain of the oncofetal fibronectin (onfFN) in the sera of HCC patients and healthy controls. We found site-specific O-glycoform alteration from T/sialyl T antigens to Tn/sialyl Tn antigens at the consecutive threonine residues 2155Thr-Thr-Ala2157 within this fragment during cancer progression. Surprisingly, this dynamic glycoform alteration is observed specifically in the patient sera diagnosed newly as stage 2-4 groups not in the normal control and stage 1 patient groups. Our results provide compelling evidence that site-specific glycoform changes observed in the onfFN IIICS domain during the tumor proliferation elaborate new class cancer stage-relevant "dynamic epitopes" as highly potential cancer diagnostic and therapeutic targets.
  • Smart Nanomedicine Targeting Endocytosis Mediated by Cancer Cell Surface Neuraminidase-1
    Ken Murakami; Daiki Kambe; Yasuhiro Yokoi; Hajime Wakui; Shun Hayakawa; Nozomi Hirane; Ryosuke Koide; Michiru Otaki; Noriko Nagahori; Shin-Ichiro Nishimura
    ADVANCED NANOBIOMED RESEARCH, 3, 12, 2023年12月
    英語, 研究論文（学術雑誌）
  • Changes in Litter Decomposition Across Succession in a Post-mined Peatland, Northern Japan
    Fumiko Takeuchi; Michiru Otaki; Shiro Tsuyuzaki
    WETLANDS, 43, 5, 2023年06月
    英語, 研究論文（学術雑誌）
  • Mouse tissue glycome atlas 2022 highlights inter-organ variation in major N-glycan profiles.
    Michiru Otaki; Nozomi Hirane; Yayoi Natsume-Kitatani; Mari Nogami Itoh; Masanori Shindo; Yoichi Kurebayashi; Shin-Ichiro Nishimura
    Scientific reports, 12, 1, 17804, 17804, 2022年10月24日, ［国際誌］
    英語, 研究論文（学術雑誌）, This study presents "mouse tissue glycome atlas" representing the profiles of major N-glycans of mouse glycoproteins that may define their essential functions in the surface glycocalyx of mouse organs/tissues and serum-derived extracellular vesicles (exosomes). Cell surface glycocalyx composed of a variety of N-glycans attached covalently to the membrane proteins, notably characteristic "N-glycosylation patterns" of the glycocalyx, plays a critical role for the regulation of cell differentiation, cell adhesion, homeostatic immune response, and biodistribution of secreted exosomes. Given that the integrity of cell surface glycocalyx correlates significantly with maintenance of the cellular morphology and homeostatic immune functions, dynamic alterations of N-glycosylation patterns in the normal glycocalyx caused by cellular abnormalities may serve as highly sensitive and promising biomarkers. Although it is believed that inter-organs variations in N-glycosylation patterns exist, information of the glycan diversity in mouse organs/tissues remains to be elusive. Here we communicate for the first-time N-glycosylation patterns of 16 mouse organs/tissues, serum, and serum-derived exosomes of Slc:ddY mice using an established solid-phase glycoblotting platform for the rapid, easy, and high throughput MALDI-TOFMS-based quantitative glycomics. The present results elicited occurrence of the organ/tissue-characteristic N-glycosylation patterns that can be discriminated to each other. Basic machine learning analysis using this N-glycome dataset enabled classification between 16 mouse organs/tissues with the highest F1 score (69.7-100%) when neural network algorithm was used. A preliminary examination demonstrated that machine learning analysis of mouse lung N-glycome dataset by random forest algorithm allows for the discrimination of lungs among the different mouse strains such as the outbred mouse Slc:ddY, inbred mouse DBA/2Crslc, and systemic lupus erythematosus model mouse MRL-lpr/lpr with the highest F1 score (74.5-83.8%). Our results strongly implicate importance of "human organ/tissue glycome atlas" for understanding the crucial and diversified roles of glycocalyx determined by the organ/tissue-characteristic N-glycosylation patterns and the discovery research for N-glycome-based disease-specific biomarkers and therapeutic targets.
  • Differences in C, N, δ13C, and δ15N among plant functional types after a wildfire in a black spruce forest, interior Alaska
    Shiro Tsuyuzaki; TaeOh Kwon; Fumiko Takeuchi; Michiru Otaki; Yuki Sawada
    Canadian Journal of Forest Research, 52, 3, 357, 364, Canadian Science Publishing, 2022年03月, ［国際誌］
    英語, 研究論文（学術雑誌）, We measured differences in %C, %N, δ13C, and δ15N of plant functional types (PFTs) between burned and unburned ground surfaces soon after a wildfire on a north-facing slope in interior Alaska. The C and N were measured for 16 species and Sphagnum litter. δ13C differed among the PFTs and was low for trees and shrubs, suggesting that woody stems slowed C dynamics or showed low water use efficiency. δ15N concentrations suggested that the herbaceous plants depended less on the mycorrhizal associations that became weak on the burned surfaces. The shrub leaves showed the lowest δ15N of PFTs and showed higher δ15N on the burned surface, showing that N transfer from the soils to the leaves in the shrubs was slowed by the wildfire. Mosses showed the highest C/N ratio. Sphagnum litter decomposed faster on the burned surface, and %N and δ15N in the litter increased from the second to third year on both burned and unburned surfaces, while %C changed little. In conclusion, the responses to the wildfire differed among the PFTs as characterized by their C and N dynamics.
  • Antiadhesive nanosome elicits role of glycocalyx of tumor cell-derived exosomes in the organotropic cancer metastasis.
    Ryosuke Koide; Nozomi Hirane; Daiki Kambe; Yasuhiro Yokoi; Michiru Otaki; Shin-Ichiro Nishimura
    Biomaterials, 280, 121314, 121314, 2022年01月, ［国際誌］
    英語, 研究論文（学術雑誌）, Despite emerging importance of tumor cells-derived exosomes in cancer metastasis, the heterogeneity of exosome populations has largely hampered systemic characterization of their molecular composition, biogenesis, and functions. This study communicates a novel method for predicting and targeting pre-metastatic sites based on an exosome model "fluorescent cancer glyconanosomes" displaying N-glycans of cultured tumor cells. Glycoblotting by antiadhesive quantum dots provides a nice tool to shed light on the pivotal functions of the glycocalyx reconstructed from four cancer cell types without bias due to other compositions of exosomes. In vivo imaging revealed that circulation, clearance, and organotropic biodistribution of cancer glyconanosomes in mice depend strongly on cancer cell-type-specific N-glycosylation patterns, the compositions of key glycotypes, particularly dominant abundances of high mannose-type N-glycans and the position-specific sialylation. Notably, organ biodistribution of cancer glyconanosomes is reproducible artificially by mimicking cancer cell-type-specific N-glycosylation patterns, demonstrating that nanosomal glycoblotting method serves as promising tools for predicting and targeting pre-metastatic sites determined by the glycocalyx of extracellular vesicles disseminated from the primary cancer site.
  • Selective reaction monitoring approach using structure-defined synthetic glycopeptides for validating glycopeptide biomarkers pre-determined by bottom-up glycoproteomics
    Kouta Shiratori; Yasuhiro Yokoi; Hajime Wakui; Nozomi Hirane; Michiru Otaki; Hiroshi Hinou; Tohru Yoneyama; Shingo Hatakeyama; Satoshi Kimura; Chikara Ohyama; Shin-Ichiro Nishimura
    RSC Advances, 12, 33, 21385, 21393, 2022年, ［国際誌］
    英語, 研究論文（学術雑誌）, Clusterin is a heavily glycosylated protein that is upregulated in various cancer and neurological diseases. The findings by the Hancock and Iliopoulos group that levels of the tryptic glycopeptide derived from plasma clusterin, 372Leu-Ala-Asn-Leu-Thr-Gln-Gly-Glu-Asp-Gln-Tyr-Tyr-Leu-Arg385 with a biantennary disialyl N-glycan (A2G2S2 or FA2G2S2) at Asn374 differed significantly prior to and after curative nephrectomy for clear cell renal cell carcinoma (RCC) patients motivated us to verify the feasibility of this glycopeptide as a novel biomarker of RCC. To determine the precise N-glycan structure attached to Asn374, whether A2G2S2 is composed of the Neu5Acα2,3Gal or/and the Neu5Acα2,6Gal moiety, we synthesized key glycopeptides having one of the two putative isomers. Selective reaction monitoring assay using synthetic glycopeptides as calibration standards allowed "top-down glycopeptidomics" for the absolute quantitation of targeted label-free glycopeptides in a range from 313.3 to 697.5 nM in the complex tryptic digests derived from serum samples of RCC patients and healthy controls. Our results provided evidence that the Asn374 residue of human clusterin is modified dominantly with the Neu5Acα2,6Gal structure and the levels of clusterin bearing an A2G2S2 with homo Neu5Acα2,6Gal terminals at Asn374 decrease significantly in RCC patients as compared with healthy controls. The present study elicits that a new strategy integrating the bottom-up glycoproteomics with top-down glycopeptidomics using structure-defined synthetic glycopeptides enables the confident identification and quantitation of the glycopeptide targets pre-determined by the existing methods for intact glycopeptide profiling.
  • Succession of litter-decomposing microbial organisms in deciduous birch and oak forests, northern Japan
    Michiru Otaki; Shiro Tsuyuzaki
    Acta Oecologica, 101, 103485, 103485, Elsevier {BV}, 2019年11月
    英語, 研究論文（学術雑誌）
  • Changes in microbial community composition in the leaf litter of successional communities after volcanic eruptions of Mount Usu, northern Japan
    Otaki, M.; Takeuchi, F.; Tsuyuzaki, S.
    Journal of Mountain Science, 13, 9, 2016年
    研究論文（学術雑誌）
■ その他活動・業績