Updated on 2024/10/02

Information

 

写真a

 
TAKESUE HIROAKI
 
Organization
Faculty of Medical Sciences Department of Basic Medicine Assistant Professor
School of Medicine Department of Medicine（Joint Appointment）
Title
Assistant Professor
Contact information
メールアドレス
Tel
0926426100
Profile
研究活動としては、合成ゲノミクスを中心とするゲノム科学の分野において新規方法論の開発を行っている。 教育活動としては、医学部医学科・生命科学科の生化学・基礎生物学を基幹教育科目を中心に従事している。
External link

Research Areas

  • Life Science / System genome science

Degree

  • Ph.D. (Pharmaceutical Science)

Research History

  • Kyushu University Department of Biochemistry  Assistant Professor

    2022.4 - Present

  • Kyushu University Department of Biochemistry Specially Appointed Assistant Professor

    2021.4 - 2022.3

    　 More details

    Country：Japan

  • Chugai Pharmaceutical Co., Ltd.

    2019.1 - 2021.3

  • Chugai Pharmaceutical Co., Ltd.

    2018.4 - 2018.12

Education

  • Kyushu University

    2015.4 - 2018.3

    　 More details

    Country： Japan

  • Kyushu University

    2013.4 - 2015.3

  • Kyushu University

    2009.4 - 2013.3

Research Interests・Research Keywords

  • Research theme：Knockout of RTT109 accelerates expansion of CUP1 arrays in budding yeast

    Keyword：Saccharomyces cerevisiae, CUP1, Cas9, histone modification, copy number variation

    Research period： 2022.4

  • Research theme：Understanding the expansion mechanism of tandem repeats by a novel method using Cas9 nickase

    Keyword：Saccaromyces cerevisiae, tandem repeat, CUP1, Cas9, copy number variation

    Research period： 2021.4 - 2022.4

Awards

  • 2023年度大会トピックス賞

    2023.3   公益社団法人　日本農芸化学会  

    武居　宏明、岡田　悟、土井　吾郎、杉山　友貴、藤和　思琴、伊藤隆司

    　More details

    遺伝子増幅の分子機構には未解明の部分が多く、そのため十分な制御が出来ず、偶然と選択に頼らざるを得ない状況が続いている。そこで我々は、出芽酵母をモデルに、制御可能な特定の分子機構に基づき、しかも選択圧を必要としない新規遺伝子増幅法BiTRExを開発した。BiTRExは、Cas9ニッケースで導入したニックによって縦列反復の隣接部位で進行中の複製フォークを崩壊させて単一末端からなるDNA 2本鎖切断を惹起し、それに対する修復機構break-induced replicationが縦列反復構造によって高い頻度で非アレリックに作動することに基づく。我々は、BiTRExによって16コピーのCUP1アレイ (約32 kb) を~500コピー (~1 Mb) にまで伸長させることに成功した。また、CUP1アレイのみならず、ENA1アレイやCUP1遺伝子座に挿入した~10 kbの反復単位からなる人工遺伝子アレイも伸長できたことから、BiTRExが合成ゲノミクスの様々な応用を可能にする汎用性のある手法と考えられた。当日は、上記研究結果を基に構築した、簡易的に複数遺伝子を増幅させる手法を紹介し、BiTRExによる遺伝子増幅の種々の研究への応用可能性を提示したい。

  • Global Education Seminar Presentation Award 2015

    2015.9   The Academy of Pharmaceutical Science and Technology, Japan  

    Hiroaki Takesue

    　More details

    Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

Papers

  • Strategic targeting of Cas9 nickase expands tandem gene arrays

    Hiroaki Takesue, Satoshi Okada, Goro Doi, Yuki Sugiyama, Emiko Kusumoto, and Takashi Ito

    bioRxiv   2024.9

    　More details

    Authorship：Lead author   Language：English  

    DOI： https://doi.org/10.1101/2024.09.10.612242

  • Characterizations of a neutralizing antibody broadly reactive to multiple gluten peptide:HLA-DQ2.5 complexes in the context of celiac disease Reviewed International journal

    Okura, Y., Ikawa-Teranishi, Y., Mizoroki, A., Takahashi, N., Tsushima, T., Irie, M., Harfuddin, Z., Miura-Okuda, M., Ito, S., Nakamura, G., @Takesue, H., Ozono, Y., Nishihara, M., Yamada, K., Gan, S. W., Hayasaka, A., Ishii, S., Wakabayashi, T., Muraoka, M., Nagaya, N., Hino, H., Nemoto, T., Kuramochi, T., Torizawa, T., Shimada, H., Kitazawa, T., Okazaki, M., Nezu, J., Sollid, L. M., Igawa, T.

    Nature communications   2023.12

    　More details

    Language：Japanese   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41467-023-44083-4

    researchmap

  • Nucleosome positioning and gene regulation of the SGLT2 gene in the renal proximal tubular epithelial cells Reviewed International journal

    Hiroaki Takesue, Takeshi Hirota, Mami Tachimura, Ayane Tokashiki, Ichiro Ieiri

    Molecular Pharmacology   94 ( 3 )   953 - 962   2018.9

    　More details

    Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)  

    DOI： 10.1124/mol.118.111807

  • Epigenetic regulation of drug transporter expression in human tissues. Invited Reviewed International journal

    Takeshi Hirota, Toshihiro Tanaka, Hiroaki Takesue, ICHIRO IEIRI

    Expert Opin Drug Metab Toxicol   13 ( 1 )   19 - 30   2017.1

    　More details

    Language：Japanese   Publishing type：Research paper (scientific journal)  

  • Exploiting mechanisms for hierarchical branching structure of lung airway Reviewed International journal

    Hisako Takigawa-Imamura, Katsumi Fumoto, Hiroaki Takesue, Takashi Miura

    PLoS ONE   2024.8

    　More details

    Language：English  

    The lung airways are characterized by long and wide proximal branches and short and thin distal branches. In this study, we investigated the emergence of this hierarchical structure through experimental observations and computational models. We focused on the branch formation in the pseudoglandular stage and examined the response of mouse lung epithelium to fibroblast growth factor 10 (FGF10) by monitoring extracellular signal-regulated kinase (ERK) activity. The ERK activity increased depending on the epithelial tissue curvature. This curvature-dependent response decreased as the development progressed. Therefore, to understand how these epithelial changes affect branching morphology, we constructed a computational model of curvature-dependent epithelial growth. We demonstrated that branch length was controlled by the curvature dependence of growth that was consistent with the experimental observations and lung morphology. However, the branching of the thin branches is suppressed in this model, which is inconsistent with the fact that thin branches in the lung are short. Thus, we introduced branch formation by apical constriction, which was shown to be regulated by Wnt signaling in our previous studies. Mathematical analysis indicated that the effect of apical constriction is cell shape-dependent, suggesting that apical constriction ameliorates the branching of thin branches. Finally, we were able to provide clarity on the hierarchical branching structure through an integrated computational model of curvature-dependent growth and cell shape regulation. We proposed that curvature-dependent growth involving FGF and Wnt-mediated cell shape regulation coordinate to control the spatial scale and frequency of branch formation.

    DOI： 10.1101/2023.03.23.533381

    researchmap

  • A cell based assay for evaluating binding and uptake of an antibody using hepatic nonparenchymal cells Reviewed

    Yuki Noguchi, Kazuhisa Ozeki, Hiroaki Takesue, Hidetaka Akita

    Scientific Reports   2021.12

    　More details

    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： https://doi.org/10.1038/s41598-021-87912-6

  • Prediction of Human Pharmacokinetics Profile of Monoclonal Antibody Using hFcRn Transgenic Mouse Model Reviewed International journal

    Genki Nakamura, Kazuhisa Ozeki, Hiroaki Takesue, Mitsuyasu Tabo, Ken-ichi Hosoya

    Biological and Pharmaceutical Bulletin   44 ( 3 )   389 - 395   2021.3

    　More details

    Language：Japanese   Publishing type：Research paper (scientific journal)  

    DOI： 10.1248/bpb.b20-00775

  • Identification and Functional Characterization of Novel Nonsynonymous Variants in the Human Multidrug and Toxin Extrusion 2-K Reviewed International journal

    Kenta Nishimura, Ryosuke Ide, Takeshi Hirota, Kana Kawazu, Shou Kodama, Hiroaki Takesue, ICHIRO IEIRI

    DRUG METABOLISM AND DISPOSITION   42 ( 9 )   2014.9

    　More details

    Language：Japanese   Publishing type：Research paper (scientific journal)  

    DOI： 10.1124/dmd.114.056887

▼display all

Presentations

  • Considering the application of BiTREx, a method for tandem repeat expansion by strategic targeting of Cas9 nickase

    2023.12 

    　More details

    Event date： 2023.12

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Country：Japan  

  • 出芽酵母を用いたCas9ニッケースの戦略的配置による縦列反復構造の伸長

    武居 宏明、岡田 悟、伊藤 隆司

    酵母遺伝学フォーラム第57回研究報告会  2024.9 

    　More details

    Event date： 2024.9

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：香川県民ホール　レグザムホール   Country：Japan  

  • 相同配列を利用して必死に生きようとする出芽酵母

    武居 宏明

    第10回酵母研究若手の会  2024.8 

    　More details

    Event date： 2024.8

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：基礎生物研究所   Country：Japan  

  • Effective sgRNA search method for Cas9 nickase-based tandem repeat expansion and its application to HEK293T cells

    Hiroaki Takesue, Satoshi Okada, Takashi Ito

    2024.6 

    　More details

    Event date： 2024.6

    Language：Japanese   Presentation type：Poster presentation  

    Country：Japan  

  • Parallel BITREx to generate a population of cells diversified in copy number ratios between target genes

    Hiroaki Takesue, Satoshi Okada, Takashi Ito

    2024.3 

    　More details

    Event date： 2024.3

    Language：Japanese   Presentation type：Oral presentation (general)  

    Country：Japan  

  • Tandem repeat expansion by strategic targeting of Cas9 nickase

    2023.11 

    　More details

    Event date： 2023.10 - 2023.11

    Language：Japanese  

    Country：Japan  

  • Parallel BiTREx to generate a population of cells diversified in copy number ratios between target genes.

    Hiroaki Takesue

    2023.10 

    　More details

    Event date： 2023.10

    Language：English  

  • 縦列反復伸長法BiTRExの展望：生産系や多重遺伝子族の創生に

    @武居 宏明

    第9回酵母研究若手の会  2023.8 

    　More details

    Event date： 2023.8

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：基礎生物研究所   Country：Japan  

  • Tandem repeat expansion by strategic targeting of Cas9 nickase

    2023.6 

    　More details

    Event date： 2023.6

    Language：Japanese  

    Country：Japan  

  • Cas9ニッケースの戦略的配置による汎用的な遺伝子増幅法の開発

    @武居 宏明、@岡田 悟、#土井 吾郎、#杉山 友貴、@藤和 思琴、@伊藤 隆司

    日本農芸化学会2023年度大会  2023.3 

    　More details

    Event date： 2023.3

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：オンライン   Country：Japan  

  • Tandem repeat expansion by strategic targeting of Cas9 nickase

    2022.12 

    　More details

    Event date： 2022.12

    Language：Japanese   Presentation type：Oral presentation (general)  

    Country：Japan  

  • Challenge to constructing stable gene over-expression system using BiTREx

    武居 宏明

    第5回さきがけCREST合同領域会議  2022.12 

    　More details

    Event date： 2022.12

    Language：Japanese  

    Venue：神戸市産業振興センター   Country：Japan  

    researchmap

  • Tandem repeat expansion by strategic targeting of Cas9 nickase

    2022.11 

    　More details

    Event date： 2022.11 - 2022.12

    Language：Japanese  

    Country：Japan  

  • Cas9 ニッケースの戦略的配置による縦列反復構造の伸長

    @武居 宏明

    第8回酵母研究若手の会  2022.10 

    　More details

    Event date： 2022.10

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：オンライン   Country：Japan  

  • Deletion of RTT109 accelerates expansion of CUP1 array in budding yeast

    2022.6 

    　More details

    Event date： 2022.6

    Language：Japanese  

    Country：Japan  

▼display all

MISC

  • Epigenetic regulation of drug transporter expression in human tissues Reviewed

    Takeshi Hirota, Toshihiro Tanaka, Hiroaki Takesue, Ichiro Ieiri

    Expert Opinion on Drug Metabolism and Toxicology   2017.1

    　More details

    Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    DOI： https://doi.org/10.1080/17425255.2017.1230199

Professional Memberships

Committee Memberships

  • Steering committee chair   Domestic

    2024.10 - 2025.9   

  • 九州大学   准教授・講師・助教候補者選考委員会  

    2024.4 - 2025.3   

    　 More details

    Committee type：Other

    researchmap

  • Steering committee member   Domestic

    2023.10 - 2024.9   

Academic Activities

  • 第15回エピジェネティクス研究会

    Role(s)： Planning, management, etc.

    （ 九州大学医学部百年講堂 Japan ） 2022.6

    　More details

    Type：Competition, symposium, etc. 

    researchmap

Research Projects

  • 構造多型への構成的アプローチ：Cas9ニッケースとスプリントDNAによる誘導

    Grant number：24K02015  2024 - 2026

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    伊藤 隆司, 岡田 悟, 武居 宏明

    　 More details

    Authorship：Coinvestigator(s)  Grant type：Scientific research funding

    本研究の目的は、任意のゲノム座位において複製フォークの崩壊を導くことによって、企図する構造多型（SV）を選択的かつ効率的に誘導することにある。先に開発したCas9ニッケース(nCas9)の戦略的配置とスプリントDNAによる縦列反復誘導法を基盤に、逆位・相互転座・クロモスリプシス様の複雑SVを相同性配列に依存せずに自在に誘導する方法論を確立し、「SVの構成生物学」とも呼ぶべき新分野の開拓を目指す。

    CiNii Research

  • 二倍体細胞におけるBITRExの検討：interchromatid vs. interhomolog BIR

    2024

    科学技術振興機構  令和6年度CREST「ゲノム合成」若手チャレンジ 

    武居　宏明

    　 More details

    Authorship：Principal investigator  Grant type：Contract research

  • Challenge to create multigene families by simultaneous induction of tandem repeat expansion and mutation

    Grant number：23K14172  2023 - 2024

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Early-Career Scientists

    　 More details

    Authorship：Principal investigator  Grant type：Scientific research funding

    CiNii Research

  • Cas9ニッケースの複数遺伝子座への同時誘導による高度な遺伝子増幅系の構築

    2023

    科学技術振興機構  令和5年度CREST「ゲノム合成」若手チャレンジ 

    武居　宏明

    　 More details

    Authorship：Principal investigator  Grant type：Contract research

  • Cas9ニッケースを用いた新手法によって遺伝子の安定な高発現系を構築する

    2022

    科学技術振興機構  令和4年度CREST「ゲノム合成」若手チャレンジ 

    武居　宏明

    　 More details

    Authorship：Principal investigator  Grant type：Contract research

Class subject

  • 薬学系キャリアデザイン

    2024.7  

  • 総合医学Ⅱ：３年次研究室配属

    2024.4 - 2025.3   Full year

  • 系統生命科学Ⅱ：生体情報機能学Ⅰ

    2023.10 - 2024.3   Second semester

  • 総合医学Ⅱ：３年次研究室配属

    2023.4 - 2024.3   Full year

  • 系統医学Ⅰ：生化学

    2023.4 - 2024.3   Full year

  • 系統医学Ⅰ：生化学

    2022.4 - 2023.3   Full year

  • 総合医学Ⅱ：３年次研究室配属

    2022.4 - 2023.3   Full year

▼display all