Updated on 2024/10/07

写真a

 
SUZUKI Hiroshi
 
Organization
Graduate School of Medicine Center for Neurological Diseases and Cance Division Professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine Department of Medicine
Title
Professor

Degree 1

  1. Ph.D. (Medical Science) ( 2010.3   The University of Tokyo ) 

Research Interests 6

  1. 相分離

  2. がん

  3. 転写

  4. エンハンサー(スーパーエンハンサー)

  5. ゲノム

  6. RNA

Research Areas 4

  1. Life Science / Pathological biochemistry  / 分子腫瘍学

  2. Life Science / Molecular biology

  3. Life Science / Genome biology

  4. Life Science / Tumor biology

Research History 9

  1. Center for One Medicine Innovative Translational Research   Professor

    2023.1

  2. Institute for Glyco-core Research (iGCORE), Nagoya University   Professor

    2021

  3. Nagoya University   Professor

    2020.5

  4. Massachusetts Institute of Technology   Koch Institute for Integrative Cancer Research   Research Scientist

    2019.6 - 2020.4

  5. Massachusetts Institute of Technology   Koch Institute for Integrative Cancer Research   Visiting Scientist

    2014.4 - 2019.3

▼display all

Education 2

  1. The University of Tokyo   Graduate School, Division of Medical Sciences

    2007.4 - 2010.3

      More details

    Country: Japan

  2. The University of Tokyo   Faculty of Medicine

    1998.4 - 2004.3

      More details

    Country: Japan

Professional Memberships 6

  1. The Japanese Cancer Association

  2. The Japanese Society of Hematology

  3. The RNA Society of Japan

  4. The Japanese Association for Molecular Target Therapy of Cancer

  5. The Molecular Biology Society of Japan

▼display all

Awards 12

  1. Bioindustry Research Award, Japan Bioindustry Association

    2023  

  2. Medical Research Encouragement Prize of The Japan Medical Association

    2022  

  3. The Young Scientists’ Prize, the Ministry of Education, Culture, Sports, Science, and Technology of Japan

    2016  

  4. Japanese Biochemical Society Young Investigator Award

    2014  

  5. Incitement Award of the Japanese Cancer Association

    2013  

▼display all

 

Papers 75

  1. Phase-separated super-enhancers confer an innate radioresistance on genomic DNA. Reviewed

    Matsumoto K, Ikliptikawati DK, Makiyama K, Mochizuki K, Tobita M, Kobayashi I, Voon DC, Lim K, Ogawa K, Kashiwakura I, Suzuki HI, Yoshino H, Wong RW, Hazawa M

    Journal of radiation research   Vol. 65 ( 4 ) page: 482 - 490   2024.7

     More details

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

    DOI: 10.1093/jrr/rrae044

    PubMed

  2. Distinct microRNA signature and suppression of ZFP36L1 define ASCL1-positive lung adenocarcinoma. Reviewed

    Enokido T, Horie M, Yoshino S, Suzuki HI, Matsuki R, Brunnström H, Micke P, Nagase T, Saito A, Miyashita N

    Molecular cancer research : MCR     2023.10

     More details

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

    DOI: 10.1158/1541-7786.MCR-23-0229

    PubMed

  3. TUG1-mediated R-loop resolution at microsatellite loci as a prerequisite for cancer cell proliferation. Reviewed International journal

    Miho M Suzuki, Kenta Iijima, Koichi Ogami, Keiko Shinjo, Yoshiteru Murofushi, Jingqi Xie, Xuebing Wang, Yotaro Kitano, Akira Mamiya, Yuji Kibe, Tatsunori Nishimura, Fumiharu Ohka, Ryuta Saito, Shinya Sato, Junya Kobayashi, Ryoji Yao, Kanjiro Miyata, Kazunori Kataoka, Hiroshi I Suzuki, Yutaka Kondo

    Nature communications   Vol. 14 ( 1 ) page: 4521 - 4521   2023.8

     More details

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

    Oncogene-induced DNA replication stress (RS) and consequent pathogenic R-loop formation are known to impede S phase progression. Nonetheless, cancer cells continuously proliferate under such high-stressed conditions through incompletely understood mechanisms. Here, we report taurine upregulated gene 1 (TUG1) long noncoding RNA (lncRNA), which is highly expressed in many types of cancers, as an important regulator of intrinsic R-loop in cancer cells. Under RS conditions, TUG1 is rapidly upregulated via activation of the ATR-CHK1 signaling pathway, interacts with RPA and DHX9, and engages in resolving R-loops at certain loci, particularly at the CA repeat microsatellite loci. Depletion of TUG1 leads to overabundant R-loops and enhanced RS, leading to substantial inhibition of tumor growth. Our data reveal a role of TUG1 as molecule important for resolving R-loop accumulation in cancer cells and suggest targeting TUG1 as a potent therapeutic approach for cancer treatment.

    DOI: 10.1038/s41467-023-40243-8

    Web of Science

    PubMed

  4. Roles of MicroRNAs in Disease Biology. Reviewed

    Hiroshi I Suzuki

    JMA journal   Vol. 6 ( 2 ) page: 104 - 113   2023.4

     More details

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

    Gene regulation by microRNAs (miRNAs) plays important roles in development, physiology, and disease. miRNAs are an abundant class of noncoding RNAs that are generated through multistep biosynthetic pathways and typically repress gene expression through target destabilization and translational inhibition. Complex interactions between miRNAs and target mRNAs are associated with characteristic molecular mechanisms, including miRNA cotargeting, target-directed miRNA degradation, and crosstalk with various RNA-binding proteins. Consistent with the broad influence on cellular function, miRNA deregulation is commonly observed in various diseases, particularly cancer, with both tumor-suppressive and oncogenic roles. Mutations in the miRNA biosynthetic pathway and several miRNA genes have been linked to diverse types of cancer and a subset of genetic diseases, respectively. Additionally, super-enhancers play important roles in the regulation of cell type-specific and disease-associated miRNAs. This review summarizes the molecular features of miRNA biogenesis and target regulation along with the roles of miRNAs in disease biology, with recent examples expanding the pathophysiological roles of miRNAs.

    DOI: 10.31662/jmaj.2023-0009

    PubMed

  5. Optimization of Cas9 activity through the addition of cytosine extensions to single-guide RNAs. Reviewed International journal

    Masaki Kawamata, Hiroshi I Suzuki, Ryota Kimura, Atsushi Suzuki

    Nature biomedical engineering   Vol. 7 ( 5 ) page: 672 - +   2023.4

     More details

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

    The precise regulation of the activity of Cas9 is crucial for safe and efficient editing. Here we show that the genome-editing activity of Cas9 can be constrained by the addition of cytosine stretches to the 5'-end of conventional single-guide RNAs (sgRNAs). Such a 'safeguard sgRNA' strategy, which is compatible with Cas12a and with systems for gene activation and interference via CRISPR (clustered regularly interspaced short palindromic repeats), leads to the length-dependent inhibition of the formation of functional Cas9 complexes. Short cytosine extensions reduced p53 activation and cytotoxicity in human pluripotent stem cells, and enhanced homology-directed repair while maintaining bi-allelic editing. Longer extensions further decreased on-target activity yet improved the specificity and precision of mono-allelic editing. By monitoring indels through a fluorescence-based allele-specific system and computational simulations, we identified optimal windows of Cas9 activity for a number of genome-editing applications, including bi-allelic and mono-allelic editing, and the generation and correction of disease-associated single-nucleotide substitutions via homology-directed repair. The safeguard-sgRNA strategy may improve the safety and applicability of genome editing.

    DOI: 10.1038/s41551-023-01011-7

    Web of Science

    PubMed

▼display all

MISC 44

  1. 生体分子凝集体と染色体外環状DNA

    芳野 聖子, 鈴木 洋

    細胞   Vol. 56 ( 6 ) page: 43 - 47   2024.6

     More details

    Authorship:Last author, Corresponding author  

  2. Biomolecular condensates and eccDNA

    Seiko Yoshino, Hiroshi I. Suzuki

    Bio Clinica   Vol. 38 ( 7 ) page: 66 - 71   2023.7

     More details

    Authorship:Last author, Corresponding author   Language:Japanese  

  3. RNA in liquid-liquid phase separation-mediated genome regulation

      Vol. 54 ( 8 ) page: 756 - 762   2022.7

     More details

    Authorship:Lead author, Last author, Corresponding author  

  4. Targeting RNA modification machineries in hematological malignancies.

      Vol. 84 ( 5 ) page: 756 - 762   2022.5

     More details

    Authorship:Lead author, Last author, Corresponding author  

  5. Now and then 〜研究の日々〜

    鈴木洋

    実験医学   Vol. 40 ( 4 ) page: 580 - 582   2022.3

     More details

    Authorship:Lead author, Last author, Corresponding author  

▼display all

KAKENHI (Grants-in-Aid for Scientific Research) 14

  1. Inhibition of microRNA functions by novel nucleic acids, iMIR

    Grant number:25640090  2013.4 - 2015.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    EGUCHI Yutaka, MURAKAMI Yoshiki, SUZUKI Hiroshi, OCHIYA Takahiro, KURODA Masahiko

      More details

    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid) 

    We developed novel nucleic acid iMIR (Inhibitor of miRNA). We constructed various iMIRs targeting miR-16 and miR-21 by joining 3 miRNA-binding sequences (MBS) containing bulge-type imperfect complementarity with amino acid amidites, and found that Gly-Gly-type iMIR and TPA-type iMIR showed strong activity to inhibit miRNA functions, assessed by luciferase reporter assay. We also found that Gly-Gly-type RNA-iMIR and TPA-type RNA-iMIR targeting miR-122 strongly inhibited replication of hepatitis C virus (HCV), and 10-fold more effective than LNAs in inhibiting HCV replication. iMIR treatment of OR6 cells reduced HCV replication without inducing interferon responses or cellular toxicity, suggesting that iMIRs are promising as novel antiviral agents. These results were published in Molecular Therapy-Nucleic Acids (2015, 4, e219).

  2. 低分子RNAネットワークのシステム的理解と新たな癌制御アプローチへの応用

    Grant number:24689018  2012.4 - 2014.3

    科学研究費助成事業  若手研究(A)

    鈴木 洋

      More details

    Authorship:Principal investigator 

    Grant amount:\26520000 ( Direct Cost: \20400000 、 Indirect Cost:\6120000 )

    本研究では、様々な病態における低分子RNAの発現異常の分子基盤となる低分子RNA生合成経路の新規調節機構、および悪性腫瘍との関係を明らかにすることを目的とする。また、低分子RNAの作動機構をネットワークレベルでシステム的に理解することを目的とする。平成24年度では、まず、miRNAによる標的mRNAの抑制効果を複数の内在性miRNAの発現量が変動する状況に外挿することが可能であるかを検討した。このために、GSEA-FAME analysis(GFA)という新規解析手法を開発し、癌のトランスクリプトームにおいてmiRNAがmRNA発現に与える負の影響が広範囲に観察されること、この原理を応用して、より頑健な新規バイオマーカーや新規治療標的をゲノムワイド発現解析から抽出できる可能性を明らかにした(Nucleic Acid Res, 41, e62)。また、これまでにMCPIP1と呼ばれるribonucleaseがmiRNAの生合成を抑制することを見出しているが、平成24年度では、MCPIP1によるmiRNA前駆体の分解を抑制するRNA結合タンパクLaとMCPIP1の関係について、乳癌の遺伝子発現データを解析し、DicerおよびLaとMCPIP1が拮抗関係にあることを見出した(J Biol Chem, 288, 723-736)。平成25年度では、GFA解析をT細胞リンパ腫の網羅的遺伝子発現解析データに拡張し、各リンパ腫サブタイプが特徴的なmiRNA活性パターンを示すことを明らかにするとともに、NPM-ALK陽性の悪性リンパ腫(未分化大細胞型リンパ腫)で発現異常が認められる複数のmiRNAの同定に成功し、mRNA発現データの解析からmiRNA―mRNAネットワークを類推できる可能性を新たに見出した(Leukemia, 27, 2107-2111)。
    25年度が最終年度であるため、記入しない。
    25年度が最終年度であるため、記入しない。
    25年度が最終年度であるため、記入しない。

  3. 低分子RNAの生合成機構の多様性と病態形成での役割に関する研究

    Grant number:23112702  2011.4 - 2013.3

    科学研究費助成事業  新学術領域研究(研究領域提案型)

    鈴木 洋

      More details

    Authorship:Principal investigator 

    Grant amount:\9360000 ( Direct Cost: \7200000 、 Indirect Cost:\2160000 )

    本研究では、マイクロRNA(miRNA)などの低分子RNAプログラムの品質管理機構の分子基盤を明らかにし、その機構の悪性腫瘍およびウイルス感染における役割を解析し、病態把握への応用の可能性を検討することを目的とする。本研究にて、MCPIP1と呼ばれる遺伝子をmiRNAによるRNAサイレンシングの負の調節因子として同定し、MCPIP1が細胞質でribonucleaseとしてmiRNA前駆体のループ部分を切断しmiRNAの生合成を終息させること、MCPIP1がmiRNAの生合成における中心的なribonucleaseであるDicerと拮抗することなどを見出し、これまで未知であったmiRNA産生を負に調節する経路を新たに発見した(Molecular Cell, 44, 424-436)。平成24年度には、MCPIP1によるmiRNA前駆体の分解を抑制するRNA結合タンパクLaとMCPIP1の関係について、乳癌の遺伝子発現データを解析し、結果として、DicerおよびLaとMCPIP1の発現量が乳癌の予後に与える影響が拮抗関係にあることを見出した(J Biol Chem, 288, 723-736)。また、癌における遺伝子発現調節ネットワークにおいて、miRNAによるネットワーク制御の意義を解明し、新規バイオマーカーや新規治療標的を見出すことを目的とし、GSEA-FAME analysis(GFA)という新規解析手法を開発した(Nucleic Acid Res, 41, e62)。
    24年度が最終年度であるため、記入しない。
    24年度が最終年度であるため、記入しない。

  4. マイクロRNAによる癌微小環境の制御・維持機構の解明

    Grant number:22890038  2010 - 2011

    科学研究費助成事業  研究活動スタート支援

    鈴木 洋

      More details

    Authorship:Principal investigator 

    Grant amount:\3146000 ( Direct Cost: \2420000 、 Indirect Cost:\726000 )

    本研究では、癌の進展を有利に導く癌微小環境の各側面(血管新生、免疫制御など)に関与するマイクロRNA(miRNA)の異常を同定し、それらのmiRNA群による癌微小環境の制御・維持機構を明らかとすることを目的とする。まず、造血器悪性腫瘍において、特徴的な染色体異常に起因する癌遺伝子の異常を伴う悪性リンパ腫に注目し、これらの腫瘍細胞で発現異常が認められるmiRNAの同定、および、その発現異常のメカニズム解析を行った。この結果、悪性リンパ腫において高発現を示すmiRNA-Xを同定し、miRNA-Xがこの癌遺伝子的異常、およびその下流の細胞内シグナル伝達経路の活性化に伴って誘導されることが明らかとなった。また、レンチウイルスを用いて特定のmiRNAの機能を阻害するシステムを樹立した。次に、このシステムとin silicoにおけるmiRNAの標的予測を組み合わせて詳細な検討を行った結果、miRNA-Xが様々な癌抑制因子を標的とすること、さらにリンパ腫細胞においてヘルハーT細胞サブセット特異的な転写因子を調節することで、リンパ腫細胞の免疫表現型を制御していることが明らかとなった。これらの結果は、悪性リンパ腫の臨床サンプルにおけるDNAマイクロアレイを用いたトランスクリプトーム解析の結果ともよく合致することをin silico解析により検討し確認した。現所沢、このmiRNA-Xが腫瘍細胞の免疫表現型に与える影響の、in vivoの腫瘍形成における意義(血管新生の促進など)、および、その修飾による治療応以下への可能性を検討している。

  5. Analysis of the mechanism of L-asparaginase to suppress the highly expressed eIF4E in NK-cell lymphoma

    Grant number:21591222  2009 - 2011

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    SUGIMOTO Koichi, SUZUKI Hiroshi, FUJIMURA Tsutomu, TAKAGI Masatoshi

      More details

    Authorship:Collaborating Investigator(s) (not designated on Grant-in-Aid) 

    We have shown two new mechanism of L-asparaginase(L-ASP), which is efficient even for chemotherapy-resistant NK-cell lymphoma. First, L-ASP decreased expression levels of various translation initiation factors including eIF4E, which in turn suppressed the translation of MYC, BCL-2 and eIF4E itself with tumor promoting and apoptosis inhibiting activities. Second, L-ASP depleted glutamine, induced TCA cycle depletion and insufficiency, and finally caused apoptosis. The result showed glutamine addiction of various lymphoid malignancies including acute lymphoblastic leukemia and the central role of TCA cycle in the suppression of apoptosis.

▼display all