Researcher Profile and Settings

Master

Affiliation (Master)

• Faculty of Advanced Life Science

Affiliation (Master)

• Faculty of Advanced Life Science

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Profile and Settings

Affiliation

• Hokkaido University, Faculty of Advanced Life Science Division of Advanced Transdisciplinary Sciences, Assistant Professor

Degree

• Doctor of Life Science（2020/12 Hokkaido University）

Profile and Settings

• Name (Japanese)

  Yokoi

• Name (Kana)

  Yasuhiro

• Name

  J-5103-2017, 202401016345809715

Affiliation

• Hokkaido University, Faculty of Advanced Life Science Division of Advanced Transdisciplinary Sciences, Assistant Professor

Achievement

Research Interests

• Organic Chemistry   Glycotechnology   Glycobiology   Bioorganic Chemistry   Chemical Biology   Medicinal Chemistry   Glycopeptide   Antibody   Drug Delivery System   

Research Areas

• Life sciences / Bioorganic chemistry
• Life sciences / Structural biochemistry
• Life sciences / Pharmaceuticals - chemistry and drug development
• Nanotechnology/Materials / Chemical biology
• Nanotechnology/Materials / Synthetic organic chemistry
• Nanotechnology/Materials / Biochemistry
• Nanotechnology/Materials / Nanobioscience

Research Experience

• 2024/02 - Today Hokkaido University Faculty of Advanced Life Science Division of Advanced Transdisciplinary Sciences Assistant Professor
• 2020/10 - 2024/01 enU Pharma, Inc. Research and Development Department Chief Researcher

Education

• 2015/04 - 2020/09  Hokkaido University  Graduate School of Life Science  Division of Life Science
• 2011/04 - 2015/03  Hokkaido University  School of Science  Biological Sciences

Published Papers

• 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) 2699-9307 2023/11/08 [Refereed]
   

  Human neuraminidase‐1 (NEU1) plays a much more profound function in human cancers than previously considered. It is demonstrated that cancer cell surface NEU1 is a desired gatekeeper for an innovative anticancer therapeutic nanomedicine enabling active drug‐targeting delivery by specific endocytosis into the cytoplasm. Nanosome, an antiadhesive nanoparticular shuttle, carrying multiple suicide substrates for NEU1 confers potent and universal inhibitory effects on the proliferation of human cancer cells, such as hepatocellular carcinoma (HCC) (HepG2, IC₅₀ = 13.5 nM), lung cancer (A549, IC₅₀ = 9.57 nM), and colon cancer (HT‐29, IC₅₀ = 11.1 nM), in which irreversible inactivation of cell surface NEU1 is essential for the intracellular trafficking and subsequent lysosomal membrane permeabilization by nanosomal aggregation due to the formation of “sialidase corona” through irreversible inactivation of NEU1–NEU4 residing in lysosome. Nanomedicine targeting membrane‐tethered NEU1 allows efficient delivery of hydrophobic sorafenib (Nexavar), a RAF family kinase inhibitor for the treatment of advanced renal cell carcinoma and unresectable HCC at the recommended dose of 400 mg orally twice daily, into endolysosome, resulting in a potent and sustainable inhibition (IC₅₀ = 3.1–6.2 nM at 24–96 h after coincubation) against HepG2 cell growth.
• Structural and molecular insight into antibody recognition of dynamic neoepitopes in membrane tethered MUC1 of pancreatic cancer cells and secreted exosomes

  Hajime Wakui, Yasuhiro Yokoi, Chieko Horidome, Toyoyuki Ose, Min Yao, Yoshikazu Tanaka, Hiroshi Hinou, Shin-Ichiro Nishimura

  RSC Chemical Biology 4 (8) 564 - 572 2023/05/24 [Refereed]
   

  We unveil for the first time that pancreatic cancer cells (PANC-1) and secreted exosomes express MUC1 bearing cancer-relevant dynamic epitopes recognized specifically by an anti-MUC1 antibody (SN-131).
• 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 2022/08/03 [Refereed]
   

  Structure-defined synthetic glycopeptides allow the validation of glycopeptide biomarkers pre-determined from bottom-up glycoproteomics based on the selective reaction monitoring approach.
• 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 0142-9612 2021/12/09 [Refereed]
  
• Effect of Site‐Specific O‐Glycosylation on the Structural Behavior of NOTCH1 Receptor Extracellular EGF‐like Domains 11 and 10

  Yasuhiro Yokoi, Shin‐Ichiro Nishimura

  Chemistry – A European Journal 26 (54) 12363 - 12372 0947-6539 2020/08/28 [Refereed]
   

  Abstract Human NOTCH1 receptor contains 36 epidermal growth factor (EGF)‐like repeating domains, in which O‐glycosylation status of EGF12 domain regulates the interaction with Notch ligands. Our interest is focused on the effect of specific O‐glycosylation states on the structural behavior of EGF11 and EGF10, because they appeared to affect molecular mechanism in receptor–ligand interactions by inducing some conformational alterations in these domains and/or the regions connecting two domains. To understand the structural impact of various O‐glycosylation patterns on the pivotal EGF‐like repeats 10, 11, and 12, we performed chemical synthesis and NMR studies of site‐specifically O‐glycosylated EGF11 and EGF10. Our strategy enabled us to synthesize four EGF11 and five EGF10 modules. The specific O‐glycosylation states affected in vitro folding of EGF10 more than EGF11, while calcium ion had a larger effect on EGF11 folding. Comprehensive NMR studies shed light on the new type “sugar bridges” crosslinking Thr‐O‐GlcNAc in the consensus sequence C5‐X‐X‐G‐X‐(T/S)‐G‐X‐X‐C6 and an amino acid in the hinge region between the domains, 445Thr‐O‐GlcNAc—IIe451 in domain 11 and 405Thr‐O‐GlcNAc—Gln411 in domain 10, respectively.
• Impaired O-Glycosylation at Consecutive Threonine TTX Motifs in Mucins Generates Conformationally Restricted Cancer Neoepitopes

  Shun Hayakawa, Takahiko Matsushita, Yasuhiro Yokoi, Hajime Wakui, Fayna Garcia-Martin, Hiroshi Hinou, Koji Matsuoka, Kazuhiro Nouso, Toshiya Kamiyama, Akinobu Taketomi, Shin-Ichiro Nishimura

  Biochemistry 59 (12) 1221 - 1241 0006-2960 2020/03/10 [Refereed]
  
• Synthetic Glycopeptides Allow for the Quantitation of Scarce Nonfucosylated IgG Fc N-Glycans of Therapeutic Antibody

  Kazuki Hammura, Akari Ishikawa, Ravi Kumar H. V., Risho Miyoshi, Yasuhiro Yokoi, Masakazu Tanaka, Hiroshi Hinou, Shin-Ichiro Nishimura

  ACS Medicinal Chemistry Letters 9 (9) 889 - 894 1948-5875 2018/08/10 [Refereed]
  
• Chemical Synthesis Demonstrates That Dynamic O-Glycosylation Regulates the Folding and Functional Conformation of a Pivotal EGF12 Domain of the Human NOTCH1 Receptor

  Shun Hayakawa, Yasuhiro Yokoi, Hiroshi Hinou, Shin-Ichiro Nishimura

  Biochemistry 56 (33) 4379 - 4391 0006-2960 2017/08/09 [Refereed]
  
• Convergent Solid-Phase Synthesis of Macromolecular MUC1 Models Truly Mimicking Serum Glycoprotein Biomarkers of Interstitial Lung Diseases

  Naoki Ohyabu, Kiyoshi Kakiya, Yasuhiro Yokoi, Hiroshi Hinou, Shin-Ichiro Nishimura

  Journal of the American Chemical Society 138 (27) 8392 - 8395 0002-7863 2016/06/29 [Refereed]
  
• Effects of the multiple O-glycosylation states on antibody recognition of the immunodominant motif in MUC1 extracellular tandem repeats

  Shobith Rangappa, Gerard Artigas, Risho Miyoshi, Yasuhiro Yokoi, Shun Hayakawa, Fayna Garcia-Martin, Hiroshi Hinou, Shin-Ichiro Nishimura

  MedChemComm 7 (6) 1102 - 1122 2040-2503 2016/03/30 [Refereed]
   

  The conformational impact of the clusteredO-glycans strongly influences recognition by antibodies of the cancer-relevant epitope in the MUC1 extracellular tandem repeat domain.

MISC

• Does glycocalyx of cancer-derived exosomes determine the future organotropism in cancer metastasis?

  大瀧みちる, 平根望巳, 村上賢, 涌井初, 西村紳一郎, 横井康広, 長堀紀子  月刊腎臓内科  18-  (1)  2023
• スパイクタンパク質の「動的エピトープ」は新型コロナウイルスの弱点?

  西村紳一郎, 涌井初, 横井康広  臨床化学  50-  (4)  2021
• NOTCH1EGFドメインにおけるO-結合型糖鎖修飾の構造および機能

  横井康広, 西村紳一郎  日本化学会春季年会講演予稿集(CD-ROM)  97th-  2017
• タウタンパクフラグメントの合成および立体構造解析

  横井康広, 早川瞬, 比能洋, 西村紳一郎  高分子学会予稿集(CD-ROM)  64-  (1)  2015

Presentations

• エクソソーム模倣ナノ粒子 "ナノソーム" によるがん細胞表面ノイラミニダーゼ-1をターゲットとした新規抗がんナノ医薬  [Not invited]

  村上賢, 横井康広, 平根望巳, 大瀧みちる, 長堀紀子, 西村紳一郎

  第10回日本細胞外小胞学会学術集会  2023/10
• がん細胞のノイラミニダーゼ1 (シアリダーゼ) を標的とするナノ医薬の創出  [Not invited]

  村上賢, 神部大貴, 横井康広, 涌井初, 平根望巳, 小出亮介, 大瀧みちる, 西村紳一郎

  第71回高分子討論会  2022/09
• Synthesis of Nanosomal Anticancer Drug Targeting Lysosomal Glycosidase  [Not invited]

  Yasuhiro Yokoi, Daiki Kambe, Shin-Ichiro Nishimura

  The 2021 International Chemical Congress of Pacific Basin Societies  2021/12
• Dynamic O-glycosylation States Regulate the Conformational Characteristics of Individual Human NOTCH1 EGF Domains  [Not invited]

  Yasuhiro Yokoi, Shin-Ichiro Nishimura

  The 2021 International Chemical Congress of Pacific Basin Societies  2021/12
• Structural Significance of Dynamic O-glycosylations in Human NOTCH1 EGF Domains  [Not invited]

  Yasuhiro Yokoi, Shin-Ichiro Nishimura

  7th International Life-Science Symposium  2019/11
• Conformational and Functional Impacts of Dynamic O-glycosylation States on Human NOTCH1 EGF Domains  [Not invited]

  Yasuhiro Yokoi, Shin-Ichiro Nishimura

  25th International Symposium on Glycoconjugates  2019/08
• NOTCH1 EGFドメインにおけるO-結合型糖鎖修飾の構造および機能  [Not invited]

  横井康広, 西村紳一郎

  日本化学会第97春季年会  2017/03
• Synthesis and Structural Analysis of Tau Glycoprotein Fragments  [Not invited]

  Yasuhiro Yokoi, Shun Hayakawa, Hiroshi Hinou, Shin-Ichiro Nishimura

  15th International Conference on Chiroptical Spectroscopy  2015/09
• タウタンパクフラグメントの合成および立体構造解析  [Not invited]

  横井康広, 早川瞬, 比能洋, 西村紳一郎

  第64回高分子学会年次大会  2015/05

Association Memberships

• The Society of Polymer Science, Japan   The Chemical Society of Japan   

Research Projects

• 免疫細胞への新規抗原提示法による疾患特異的抗体の効率的創出

  ノーステック財団：札幌バイオシーズ事業化支援事業 札幌バイオシーズ事業化支援補助金 (健康・医療・バイオ分野)

  Date (from‐to) : 2023/08 -2024/03 

  Author : 西村紳一郎, 横井康広
• 高性能ナノ微粒子「ナノソーム」へのsiRNA搭載法の確立

  ノーステック財団：若手研究人材育成事業 若手研究人材・ネットワーク育成補助金

  Date (from‐to) : 2021/08 -2022/03 

  Author : 横井康広