Education 【 display / non-display 】

Education 【 display / non-display 】

• 2007

  -

  2010

  Akita University   Graduate School of Engineering and Resource Science   Department of Advanced Materials Engineering  

• 2005

  -

  2007

  Akita University   Graduate School of Engineering and Resource Science   Department of Materials-process Engineering and Applied Chemistry for Environments  

• 2001

  -

  2005

  Akita University   Faculty of Engineering and Resource Science   環境物質工学科  

Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2016.04

  -

  2018.03

  Northwestern大学   Department of Cell and Molecular Biology   客員研究員

  客員研究員

• 2011.06

  -

  Now

  Sapporo Medical University   School of Medicine   助教

  助教

• 2010.04

  -

  2011.05

  Akita University   博士研究員

  博士研究員

Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Virology   RNAウィルス

• Life sciences   Pharmaceuticals - health and biochemistry  

• Life sciences   Immunology   自然免疫

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   医学部   助教  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• 分子シャペロン

• 自然免疫

• 炎症

• ミトコンドリア

• Toll-like receptor

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Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Bacillaceae serine proteases and Streptomyces epsilon-poly-l-lysine synergistically inactivate Caliciviridae by inhibiting RNA genome release

  Soh Yamamoto, Noriko Ogasawara, Yuka Sudo-Yokoyama, Sachiko Sato, Nozomu Takata, Nana Yokota, Tomomi Nakano, Kyoko Hayashi, Akira Takasawa, Mayumi Endo, Masako Hinatsu, Keitaro Yoshida, Toyotaka Sato, Satoshi Takahashi, Kenichi Takano, Takashi Kojima, Jun Hiraki, Shin-ich Yokota

  Scientific Reports ( Springer Science and Business Media LLC )  14 ( 1 )  2024.07  [Refereed]

  Authorship：   Lead author

  　View Summary

  Abstract Human norovirus (HuNoV) is an enteric infectious pathogen belonging to the Caliciviridae family that causes occasional epidemics. Circulating alcohol-tolerant viral particles that are readily transmitted via food-borne routes significantly contribute to the global burden of HuNoV-induced gastroenteritis. Moreover, contact with enzymes secreted by other microorganisms in the environment can impact the infectivity of viruses. Hence, understanding the circulation dynamics of Caliciviridae is critical to mitigating epidemics. Accordingly, in this study, we screened whether environmentally abundant secretase components, particularly proteases, affect Caliciviridae infectivity. Results showed that combining Bacillaceae serine proteases with epsilon-poly-l-lysine (EPL) produced by Streptomyces—a natural antimicrobial—elicited anti-Caliciviridae properties, including against the epidemic HuNoV GII.4_Sydney_2012 strain. In vitro and in vivo biochemical and virological analyses revealed that EPL has two unique synergistic viral inactivation functions. First, it maintains an optimal pH to promote viral surface conformational changes to the protease-sensitive structure. Subsequently, it inhibits viral RNA genome release via partial protease digestion at the P2 and S domains in the VP1 capsid. This study provides new insights regarding the high-dimensional environmental interactions between bacteria and Caliciviridae, while promoting the development of protease-based anti-viral disinfectants.

  DOI

• Multilayered proteomics reveals that JAM-A promotes breast cancer progression via regulation of amino acid transporter LAT1.

  Kazufumi Magara, Akira Takasawa, Kumi Takasawa, Tomoyuki Aoyama, Misaki Ota, Daisuke Kyuno, Yusuke Ono, Taro Murakami, Soh Yamamoto, Yuna Nakamori, Naoya Nakahashi, Goro Kutomi, Ichiro Takemasa, Tadashi Hasegawa, Makoto Osanai

  Cancer science    2024.06  [Refereed]  [International journal]

  　View Summary

  Recent studies have shown that transmembrane-type tight junction proteins are upregulated in various cancers compared with their levels in normal tissues and are involved in cancer progression, suggesting that they are potential therapeutic targets. Here, we demonstrated the expression profile and a novel role of junctional adhesion molecule-A (JAM-A) in breast cancer. Immunohistochemistry of surgical specimens showed that JAM-A was highly expressed from carcinoma in situ lesions, as in other adenocarcinomas, with higher expression in invasive carcinomas. High expression of JAM-A contributed to malignant aspects such as lymph node metastasis and lymphatic involvement positivity. In breast cancer cells, JAM-A expression status affects malignant potentials including proliferation and migration. Multilayered proteomics revealed that JAM-A interacts with the amino acid transporter LAT1 in breast cancer cells. JAM-A regulates the expression of LAT1 and interacts with it on the whole cell membrane, leading to enhanced amino acid uptake to promote tumor growth. Double high expression of JAM-A and LAT1 predicts poor prognosis in patients with breast cancer. Of note, an antibody against an extracellular domain of JAM-A suppressed the proliferation of breast cancer cells. Our findings indicate the possibility of JAM-A-targeted therapy ideally combined with LAT1-targeted therapy as a new therapeutic strategy against breast cancer.

  DOI PubMed

• The clarithromycin-binding proteins NIPSNAP1 and 2 regulate cytokine production through mitochondrial quality control.

  Soh Yamamoto, Noriko Ogasawara, Yukari Mitsuhashi, Kenichi Takano, Shin-Ichi Yokota

  Scientific reports   14 ( 1 ) 2354 - 2354  2024.01  [Refereed]  [International journal]

  Authorship：   Lead author

  　View Summary

  The mechanism underlying the anti-inflammatory effect of macrolide antibiotics, such as clarithromycin (CAM), remains to be clarified. The CAM-binding proteins 4-nitrophenylphosphatase domain and non-neuronal synaptosomal associated protein 25 (SNAP25)-like protein homolog (NIPSNAP) 1 and 2 are involved in the immune response and mitochondrial homeostasis. However, the axis between CAM-NIPSNAP-mitochondria and Toll-like receptor (TLR) and their molecular mechanisms remain unknown. In this study, we sought to elucidate the relationship between mitochondrial homeostasis mediated by NIPSNAP1 and 2 and the immunomodulatory effect of CAM. NIPSNAP1 or 2 knockdown (KD) by RNA interference impaired TLR4-mediated interleukin-8 (IL-8) production. Similar impairment was observed upon treatment with mitochondrial function inhibitors. However, IL-8 secretion was not impaired in NIPSNAP1 and 2 individual knockout (KO) and double KO (DKO) cells. Moreover, the oxygen consumption rate (OCR) in mitochondria measured using a flex analyzer was significantly reduced in NIPSNAP1 or 2 KD cells, but not in DKO cells. CAM also dose-dependently reduced the OCR. These results indicate that CAM suppresses the IL-8 production via the mitochondrial quality control regulated by temporary functional inhibition of NIPSNAP1 and 2. Our findings provide new insight into the mechanisms underlying cytokine production, including the TLR-mitochondria axis, and the immunomodulatory effects of macrolides.

  DOI PubMed

• Affinity of β-Lactam Antibiotics for Neisseria gonorrhoeae Penicillin-Binding Protein 2 Having Wild, Cefixime-Reduced-Susceptible, and Cephalosporin (Ceftriaxone)-Resistant penA Alleles.

  Yoshiki Hiyama, Soh Yamamoto, Toyotaka Sato, Noriko Ogasawara, Naoya Masumori, Satoshi Takahashi, Shin-Ichi Yokota

  Microbial drug resistance (Larchmont, N.Y.)    2024.01  [Refereed]  [International journal]

  Authorship：   Lead author

  　View Summary

  Multidrug-resistant Neisseria gonorrhoeae is a serious concern worldwide. Resistance to β-lactam antibiotics occurs through mutations in penicillin-binding proteins (PBPs), acquisition of β-lactamases, and alteration of antibiotic penetration. Mosaic structures of penA, which encodes PBP2, play a major role in resistance to β-lactams, especially cephalosporins. Ceftriaxone (CRO) is recognized as the only satisfiable antibiotic for the treatment of gonococcal infections; however, CRO-resistant isolates have emerged in the community. Here, we examined the affinity of β-lactam antibiotics for recombinant PBP2 in a competition assay using fluorescence-labeled penicillin. We found no or little difference in the affinities of penicillins and meropenem (MEM) for PBP2 from cefixime (CFM)-reduced-susceptible strain and cephalosporin-resistant strain. However, the affinity of cephalosporins, including CRO, for PBP2 from the cephalosporin-resistant strain was markedly lower than that for PBP2 from the CFM-reduced-susceptible-resistant strain. Notably, piperacillin (PIP) showed almost the same affinity for PBP2 from penicillin-susceptible, CFM-reduced-susceptible, and cephalosporin (including CRO)-resistant strains. Thus, PIP/tazobactam and MEM are candidate antibiotics for the treatment of CRO-resistant/multidrug-resistant N. gonorrhoeae.

  DOI PubMed

• Serotype replacement and an increase in non-encapsulated isolates among community-acquired infections of Streptococcus pneumoniae during post-vaccine era in Japan.

  Shin-Ichi Yokota, Naoyuki Tsukamoto, Toyotaka Sato, Yasuo Ohkoshi, Soh Yamamoto, Noriko Ogasawara

  IJID regions   8   105 - 110  2023.09  [Refereed]  [International journal]

  　View Summary

  OBJECTIVES: It is feared that the serotype replacement of Streptococcus pneumoniae occurred by the introduction of pneumococcal vaccines as periodical inoculation leads to reduced efficacy of the approved vaccines and altered antimicrobial susceptibility. METHODS: We determined serotypes of 351 S. pneumoniae isolates collected at a commercial clinical laboratory in Hokkaido prefecture, Japan, from December 2018 to February 2019 by using the polymerase chain reaction procedure of the US Centers for Disease Control and Prevention. Antimicrobial susceptibility and resistance gene profiles were also examined. RESULTS: Vaccine coverage rates were 7.9% for 13-valent conjugate vaccine, and 32.5% for 23-valent polysaccharide vaccine, respectively. Non-typable strains were 19.7%. cpsA-positive isolates (group I), and null capsule clade (NCC)1, NCC2 and NCC3 (group II) comprised 31.3%, 28.4%, 32.8%, and 7.5% of the 69 non-typable strains, respectively. No penicillin-resistant/intermediate isolates were found; however, serotypes 35B and 15A/F showed low susceptibility to β-lactams. Only five strains (1.4%) were levofloxacin-resistant, and all were from the older persons, and three strains were serotype 35B. CONCLUSION: The progression of serotype replacement in non-invasive pneumococcal infections has occurred during the post-vaccine era in Japan, and non-encapsulated isolates, such as NCC, have increased. Antimicrobial susceptibility is not worsened.

  DOI PubMed

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Books and Other Publications 【 display / non-display 】

Books and Other Publications 【 display / non-display 】

• 14, 15員環マクロライド系抗菌薬の免疫調節作用とミトコンドリア代謝機能

  山本 聡, 小笠原 徳子, 三橋 由佳梨, 高野 賢一, 横田 伸一( Part： Joint author)

  エンドトキシン・自然免疫研究  2024.05

Misc 【 display / non-display 】

Misc 【 display / non-display 】

• Novel antimicrobial activities of a peptide derived from a Japanese soy-bean fermented food, Natto

  北川学, 北川学, 白石宗, 山本聡, 久富亮佑, 佐藤豊孝, 小笠原徳子, 宮本篤, 横田伸一

  日本細菌学雑誌(Web)   72 ( 1 )  2017

  J-GLOBAL

• 納豆由来ペプチドの特異な殺菌効果とその作用機序

  白石宗, 北川学, 山本聡, 久富亮佑, 佐藤豊孝, 涌井秀樹, 伊藤英晃, 宮本篤, 横田伸一

  エンドトキシン・自然免疫研究20－自然免疫における化学生物学の貢献－ ( 日本エンドトキシン・自然免疫研究会 )  20   39 - 42  2017

  Article, review, commentary, editorial, etc. (other)  

• タゾバクタム/ピペラシリン耐性大腸菌の耐性機構の解析

  鈴木裕樹, 佐藤豊孝, 山本聡, 小笠原徳子, 白石宗, 品川雅明, 高橋聡, 高橋聡, 横田伸一

  日本細菌学雑誌(Web)   72 ( 1 )  2017

  J-GLOBAL

• 対数期におけるLactobacillus gasseri JCM1131^Tのリポテイコ酸の局在

  白石宗, 横田伸一, 佐藤耶舞羽, 伊藤利章, 吹谷智, 山本聡, 小笠原徳子, 佐藤豊孝, 横田篤

  日本農芸化学会大会講演要旨集(Web)   2016  2016

  J-GLOBAL

• 哺乳類HSP60の新規基質であるNIP-SNAP2タンパク質の機能

  山本聡, 小笠原徳子, 白石宗, 佐藤豊孝, 氷見徹夫, 伊藤英晃, 横田伸一

  臨床ストレス応答学会大会抄録集   10th  2015

  J-GLOBAL

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Awards 【 display / non-display 】

Awards 【 display / non-display 】

• United Japanese Researchers Around the World paper award

  2020.03   United Japanese Reserchers Around the World   Differential roles of chronic autophagy in insulin production and sensitivity., Cell Reports, 2018, 23, 3286-3299.

• 海外留学助成金

  2016.03   上原記念生命科学財団  

  Winner： 山本聡

• 海外留学助成金

  2016.03   伊藤医薬学術交流財団  

  Winner： 山本聡

Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• 納豆菌が分泌するRSウイルス不活化物質の同定と作用機序の解明

  Project Year :

  2024.04

  -

  2025.03

   

  Authorship： Principal investigator

• 納豆菌が分泌するRSウイルス不活化物質の同定と作用機序の解明

  Project Year :

  2024.04

  -

  2025.03

   

  Authorship： Principal investigator

• 深在性真菌症のFFPE組織を用いた分子形態学的な同定および解析方法の確立

  基盤研究(C)

  Project Year :

  2022.04

  -

  2025.03

   

  青山 智志, 高澤 啓, 山本 聡

• Identification of host factors for Respiratory syncytial virus

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2022.04

  -

  2025.03

   

  山本 聡, 小笠原 徳子, 高澤 啓

• 次世代の耐性菌対策を考慮した、国際的ハイリスク病原性細菌の市中内定着様式の解明

  基盤研究(B)

  Project Year :

  2021.04

  -

  2024.03

   

  佐藤 豊孝, 浦野 恵美子, 青木 弘太郎, 中島 千絵, 臼井 優, 鈴木 仁人, 大久保 寅彦, 福田 昭, 小笠原 徳子, 山本 聡

  　View Summary

  本研究では、フルオロキノロン耐性大腸菌ST131をモデルに、『院内』で問題となるAMR感染症を『院外(市中)』からのプローチでその伝播・定着様式を明らかにすることで、現行のAMR対策が報われない国際的なAMR問題の根本的解決に繋がる次世代型(院内-市中一体型)AMR対策に資する科学的知見を提供することが本研究の目的である。本目的達成の為、本年度は、ST131の伝播状況と伝播様式および定着メカニズム(定着因子の同定)を行なった。具体的には、同一地域（札幌市内）から同一時期に院内及び市中の各サンプル群(患者、健常者、動物、環境)から大腸菌を一斉に分離した。その後、シプロフロキサシンに耐性だった株を対象にST131の検出PCRおよび次世代シーケンス解析により行なった。その結果、ヒトの臨床検体(大学病院)からは25%, ヒトの臨床検体(市中クリニック)からは19.2%, ヒトの健常者の便検体からは16.1%, 伴侶動物(犬や猫)の直腸スワブからは18.3%, 家畜の牛、豚、鶏の便検体からはそれぞれ9.5%, 0%, 6.7%のフルオロキノロン耐性率であった。分離大腸菌全体に占めるST131の割合は、ヒトの臨床検体(大学病院)からは12.5%, ヒトの臨床検体(市中クリニック)からは5.7%, ヒトの健常者の便検体からは8.2%, 伴侶動物(犬や猫)の直腸スワブからは15.9%, 家畜の牛、豚、鶏の便検体からは1株も分離されなかった。

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Presentations 【 display / non-display 】

Presentations 【 display / non-display 】

• Syntaxin17とVAMP8は感染性ヒトRSウイルス粒子の産生に関与する

  山本聡, 小笠原徳子, 横田伸一

  日本ウイルス学会 

  Presentation date： 2024.11

  Event date：

  2024.11

  　

  　

• カリシウイルス科に対するウイルスタンパク質不活化酵素としての天然物由来セリンプロ テアーゼとイプシロン-ポリ-L-リジンの組み合わせ

  日本ウイルス学会北海道支部会 第56回 夏季シンポジウム 

  Presentation date： 2023.07

• Syntaxin17 and VAMP8 are involved in generating human respiratory syncytial viral particles.

  日本ウイルス学会北海道支部 第57回 夏季シンポジウム 

  Presentation date： 2024.07

Teaching Experience 【 display / non-display 】

Teaching Experience 【 display / non-display 】

• ウイルス学  

  西野学園 (臨床検査科)  

  2018.04

  -

  Now

   

• ウイルス学  

  札幌医科大学  

  2018.04

  　

  　

   

• 微生物学実習  

  札幌医科大学  

  2010.04