Details of the Researcher

PHOTO

Yuki Yoshino
Section
Tohoku University Hospital
Job title
Assistant Professor
Degree

  • Ph.D. in Medicine (Tohoku University)

Research History 4

  • 2026/07 - Present
    Tohoku University

  • 2015/09 - 2026/06
    Tohoku University　Department of Cancer Biology, Institute of Aging, Development, and Cancer　Assistant Proffessor

  • 2015/04 - 2015/08
    Tohoku University　Department of Cancer Biology, Institute of Aging, Development, and Cancer　Research associate

  • 2009/04 - 2011/03
    Tohoku University　Tohoku University Hospital　resident

Education 2

  • Tohoku University　Graduate school of Medicine　Medical Sciences

    2011/04 - 2015/03

  • Tohoku University　School of Medicine

    2003/04 - 2009/03

Professional Memberships 4

  • 日本臨床腫瘍学会

  • 日本がん治療学会

  • 日本癌学会

  • 日本内科学会

Research Areas 1

  • Life sciences / Human pathology / Molecular Oncology

Awards 8

  1. 第63回 渡辺記念特別奨励賞

    2023/06　公益財団法人 UBE学術振興財団

  2. 第20回インテリジェント・コスモス奨励賞

    2021/04　公益財団法人 インテリジェント・コスモス学術振興財団

  3. 匂坂記念賞

    2020/07　艮陵医学振興会

  4. 研究奨励賞

    2020/01　東北大学 加齢医学研究所

  5. 奨学賞A

    2020/01　東北医学会

  6. 総長賞

    2009/03　東北大学

  7. 平成20年度優秀学生顕彰事業 学術部門大賞

    2008/12　独立行政法人 日本学生支援機構

  8. 医学部学生奨学賞

    2007/01　東北大学医学部

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Papers 34

  1. Evaluating homologous recombination activity in tissues to predict the risk of hereditary breast and ovarian cancer and olaparib sensitivity. Peer-reviewed

    Motonari T, Yoshino Y, Haruta M, Endo S, Sasaki S, Miyashita M, Tada H, Watanabe G, Kaneko T, Ishida T, Chiba N

    Scientific Reports　14　7519　2024/04

    DOI： 10.1038/s41598-024-57367-6 　

  2. Knockout of Brca1-interacting factor Ola1 in female mice induces tumors with estrogen suppressible centrosome amplification. International-journal Peer-reviewed

    Yuki Yoshino, Honami Ogoh, Yudai Iichi, Tomohiro Sasaki, Takahiro Yoshida, Shiori Ichimura, Masahiro Nakayama, Wu Xi, Hiroki Fujita, Megumi Kikuchi, Zhenzhou Fang, Xingming Li, Takaya Abe, Mitsuru Futakuchi, Yasuhiro Nakamura, Toshio Watanabe, Natsuko Chiba

    Biochimica et biophysica acta. Molecular basis of disease　167138-167138　2024/03/25

    DOI： 10.1016/j.bbadis.2024.167138 　

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    Obg-like ATPase 1 (OLA1) is a binding protein of Breast cancer gene 1 (BRCA1), germline pathogenic variants of which cause hereditary breast cancer. Cancer-associated variants of BRCA1 and OLA1 are deficient in the regulation of centrosome number. Although OLA1 might function as a tumor suppressor, the relevance of OLA1 deficiency to carcinogenesis is unclear. Here, we generated Ola1 knockout mice. Aged female Ola1+/- mice developed lymphoproliferative diseases, including malignant lymphoma. The lymphoma tissues had low expression of Ola1 and an increase in the number of cells with centrosome amplification. Interestingly, the proportion of cells with centrosome amplification in normal spleen from Ola1+/- mice was higher in male mice than in female mice. In human cells, estrogen stimulation attenuated centrosome amplification induced by OLA1 knockdown. Previous reports indicate that prominent centrosome amplification causes cell death but does not promote tumorigenesis. Thus, in the current study, the mild centrosome amplification observed under estrogen stimulation in Ola1+/- female mice is likely more tumorigenic than the prominent centrosome amplification observed in Ola1+/- male mice. Our findings provide a possible sex-dependent mechanism of the tumor suppressor function of OLA1.

  3. Aurora A polyubiquitinates the BRCA1-interacting protein OLA1 to promote centrosome maturation. International-journal Peer-reviewed

    Zhenzhou Fang, Xingming Li, Yuki Yoshino, Moe Suzuki, Huicheng Qi, Hinari Murooka, Riko Katakai, Matsuyuki Shirota, Thi Anh Mai Pham, Ayako Matsuzawa, Kei Otsuka, Chikashi Ishioka, Takahiro Mori, Natsuko Chiba

    Cell reports　42　(8)　112850-112850　2023/07/21

    DOI： 10.1016/j.celrep.2023.112850 　

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    The BRCA1-interacting protein Obg-like ATPase 1 (OLA1) functions in centriole duplication. In this study, we show the role of the mitotic kinase Aurora A in the reduction of centrosomal OLA1. Aurora A binds to and polyubiquitinates OLA1, targeting it for proteasomal degradation. NIMA-related kinase 2 (NEK2) phosphorylates the T124 residue of OLA1, increases binding of OLA1 to Aurora A and OLA1 polyubiquitination by Aurora A, and reduces centrosomal OLA1 in G2 phase. The kinase activity of Aurora A suppresses OLA1 polyubiquitination. The decrease in centrosomal OLA1 caused by Aurora A-mediated polyubiquitination promotes the recruitment of pericentriolar material proteins in G2 phase. The E3 ligase activity of Aurora A is critical for centrosome amplification induced by its overexpression. The results suggest a dual function of Aurora A as an E3 ubiquitin ligase and a kinase in the regulation of centrosomal OLA1, which is essential for proper centrosome maturation in G2 phase.

  4. BRCA1 transports the DNA damage signal for CDDP-induced centrosome amplification through the centrosomal Aurora A. International-journal Peer-reviewed

    Huicheng Qi, Megumi Kikuchi, Yuki Yoshino, Zhenzhou Fang, Kazune Ohashi, Takato Gotoh, Ryo Ideta, Ayako Ui, Shino Endo, Kei Otsuka, Norihisa Shindo, Kohsuke Gonda, Chikashi Ishioka, Yoshio Miki, Tokuro Iwabuchi, Natsuko Chiba

    Cancer science　113　(12)　4230-4243　2022/09/09

    DOI： 10.1111/cas.15573 　

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    Breast cancer gene 1 (BRCA1) plays roles in DNA repair and centrosome regulation and is involved in DNA damage-induced centrosome amplification (DDICA). Here, the centrosomal localization of BRCA1 and the kinases involved in centrosome duplication were analyzed in each cell cycle phase after treatment with DNA crosslinker cisplatin (CDDP). CDDP treatment increased the centrosomal localization of BRCA1 in early S-G2 phase. BRCA1 contributed to the increased centrosomal localization of Aurora A in S phase and that of phosphorylated Polo-like kinase 1 (PLK1) in late S phase after CDDP treatment, resulting in centriole disengagement and overduplication. The increased centrosomal localization of BRCA1 and Aurora A induced by CDDP treatment involved the nuclear export of BRCA1 and BRCA1 phosphorylation by ataxia telangiectasia mutated (ATM). Patient-derived variants and mutations at phosphorylated residues of BRCA1 suppressed the interaction between BRCA1 and Aurora A, as well as the CDDP-induced increase in the centrosomal localization of BRCA1 and Aurora A. These results suggest that CDDP induces the phosphorylation of BRCA1 by ATM in the nucleus and its transport to the cytoplasm, thereby promoting the centrosomal localization Aurora A, which phosphorylates PLK1. The function of BRCA1 in the translocation of the DNA damage signal from the nucleus to the centrosome to induce centrosome amplification after CDDP treatment might support its role as a tumor suppressor.

  5. BRCA1/ATF1-mediated transactivation is involved in resistance to PARP inhibitors and cisplatin International-journal Peer-reviewed

    Shino Endo, Yuki Yoshino, Matsuyuki Shirota, Gou Watanabe, Natsuko Chiba

    Cancer Research Communications　1　(2)　90-105　2021/11

    DOI： 10.1158/2767-9764.CRC-21-0064 　

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    UNLABELLED: Homologous recombination (HR)-deficient cells are sensitive to PARP inhibitors through a synthetic lethal effect. We previously developed an HR activity assay named Assay of Site-Specific HR Activity (ASHRA). Here, we evaluated the HR activity of 30 missense variants of BRCA1 by ASHRA and found that several BRCA1 variants showed intermediate HR activity, which was not clearly discerned by our previous analyses using a conventional method. HR activity measured by ASHRA was significantly correlated with sensitivity to olaparib. However, cells expressing the severely HR-deficient BRCA1-C61G variant were resistant to olaparib, and resistance was dependent on high expression of activating transcription factor 1 (ATF1), which binds to BRCA1 and activates the transcription of target genes to regulate cell proliferation. The BRCA1-C61G variant bound to ATF1 and stimulated ATF1-mediated transactivation similar to wild-type BRCA1. High expression of ATF1 conferred resistance to olaparib and cisplatin activating BRCA1/ATF1-mediated transcription without affecting HR activity in BRCA2-knockdown or RAD51-knockdown cells, but not in BRCA1-knockdown cells. These results suggest that ASHRA is a useful method to evaluate HR activity in cells and to predict the sensitivity to PARP inhibitors. The expression level of ATF1 might be an important biomarker of the effect of PARP inhibitors and platinum agents on HR-deficient tumors with the BRCA1-C61G variant or alteration of non-BRCA1 HR factors such as BRCA2 and RAD51. SIGNIFICANCE: ASHRA could evaluate HR activity in cells and predict the sensitivity to PARP inhibitors. High expression level of ATF1 may predict the resistance of BRCAness tumors with alterations of non-BRCA1 HR factors to PARP inhibitors and platinum agents.

  6. RACK1 regulates centriole duplication through promoting the activation of polo-like kinase 1 by Aurora A. International-journal Peer-reviewed

    Yuki Yoshino, Akihiro Kobayashi, Huicheng Qi, Shino Endo, Zhenzhou Fang, Kazuha Shindo, Ryo Kanazawa, Natsuko Chiba

    Journal of cell science　133　(17)　2020/09/01

    DOI： 10.1242/jcs.238931 　

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    Breast cancer gene 1 (BRCA1) contributes to the regulation of centrosome number. We previously identified receptor for activated C kinase 1 (RACK1) as a BRCA1-interacting partner. RACK1, a scaffold protein that interacts with multiple proteins through its seven WD40 domains, directly binds to BRCA1 and localizes to centrosomes. RACK1 knockdown suppresses centriole duplication, whereas RACK1 overexpression causes centriole overduplication in a subset of mammary gland-derived cells. In this study, we showed that RACK1 binds directly to polo-like kinase 1 (PLK1) and Aurora A, and promotes the Aurora A-PLK1 interaction. RACK1 knockdown decreased phosphorylated PLK1 (p-PLK1) levels and the centrosomal localization of Aurora A and p-PLK1 in S phase, whereas RACK1 overexpression increased p-PLK1 level and the centrosomal localization of Aurora A and p-PLK1 in interphase, resulting in an increase of cells with abnormal centriole disengagement. Overexpression of cancer-derived RACK1 variants failed to enhance the Aurora A-PLK1 interaction, PLK1 phosphorylation and the centrosomal localization of p-PLK1. These results suggest that RACK1 functions as a scaffold protein that promotes the activation of PLK1 by Aurora A in order to promote centriole duplication.This article has an associated First Person interview with the first author of the paper.

  7. RACK1 regulates centriole duplication by controlling localization of BRCA1 to the centrosome in mammary tissue-derived cells. International-journal Peer-reviewed

    Yuki Yoshino, Huicheng Qi, Ryo Kanazawa, Mami Sugamata, Kenta Suzuki, Akihiro Kobayashi, Kazuha Shindo, Ayako Matsuzawa, Shun Shibata, Shino Endo, Yutaro Miyanishi, Tatsuro Shimaoka, Chikashi Ishioka, Shin-Ichiro Kanno, Akira Yasui, Natsuko Chiba

    Oncogene　38　(16)　3077-3092　2019/04

    DOI： 10.1038/s41388-018-0647-8 　

    ISSN： 0950-9232

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    Breast cancer gene 1 (BRCA1) is a tumor suppressor that is associated with hereditary breast and ovarian cancer. BRCA1 functions in DNA repair and centrosome regulation together with BRCA1-associated RING domain protein (BARD1), a heterodimer partner of BRCA1. Obg-like ATPase 1 (OLA1) was identified as a protein that interacts with BARD1. OLA1 regulates the centrosome by binding to and collaborating with BRCA1 and BARD1. We identified receptor for activated C kinase (RACK1) as a protein that interacts with OLA1. RACK1 directly bound to OLA1, the N-terminal region of BRCA1, and γ-tubulin, associated with BARD1, and localized the centrosomes throughout the cell cycle. Knockdown of RACK1 caused abnormal centrosomal localization of BRCA1 and abrogated centriole duplication. Overexpression of RACK1 increased the centrosomal localization of BRCA1 and caused centrosome amplification due to centriole overduplication. The number of centrioles in cells with two γ-tubulin spots was higher in cell lines derived from mammary tissue compared to those derived from other tissues. The effects of aberrant RACK1 expression level on centriole duplication were observed in cell lines derived from mammary tissue, but not in those derived from other tissues. Two BRCA1 variants, R133H and E143K, and a RACK1 variant, K280E, associated with cancer, which weakened the BRCA1-RACK1 interaction, interfered with the centrosomal localization of BRCA1 and reduced centrosome amplification induced by overexpression of RACK1. These results suggest that RACK1 regulates centriole duplication by controlling the centrosomal localization of BRCA1 in mammary tissue-derived cells and that this is dependent on the BRCA1-RACK1 interaction.

  8. Evaluation of site-specific homologous recombination activity of BRCA1 by direct quantitation of gene editing efficiency. International-journal Peer-reviewed

    Yuki Yoshino, Shino Endo, Zhenghao Chen, Huicheng Qi, Gou Watanabe, Natsuko Chiba

    Scientific reports　9　(1)　1644-1644　2019/02/07

    DOI： 10.1038/s41598-018-38311-x 　

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    Homologous recombination (HR) contributes to the repair of DNA double-strand breaks (DSBs) and inter-strand crosslinks. The HR activity in cancer cells can be used to predict their sensitivity to DNA-damaging agents that cause these damages. To evaluate HR activity, we developed a system called Assay for Site-specific HR Activity (ASHRA), in which cells are transiently transfected with an expression vector for CRISPR/Cas9 and a HR donor sequence containing a marker gene. DSBs are created by Cas9 and then repaired by HR using donor vector sequences homologous to the target gene. The level of genomic integration of the marker gene is quantified by Western blotting, flowcytometry, or quantitative PCR (qPCR). ASHRA detected HR deficiency caused by BRCA1, BARD1, or RAD51 knockdown or introduction of BRCA1 variants. The influence of BRCA1 variants on HR, as determined by qPCR, was consistent with the chemosensitivities of the transfected cells. The qPCR format of ASHRA could measure HR activity in both transcribed and un-transcribed regions. Knockdown of BRCA1 nor BARD1 did not affect HR activity in a transcriptionally inactive site. ASHRA can evaluate HR activity and will be useful for predicting sensitivity to chemotherapy, screening drugs that affect HR, and investigating the mechanisms of HR.

  9. BRCA1-Interacting Protein OLA1 Requires Interaction with BARD1 to Regulate Centrosome Number. International-journal Peer-reviewed

    Yuki Yoshino, Huicheng Qi, Hiroki Fujita, Matsuyuki Shirota, Shun Abe, Yuhei Komiyama, Kazuha Shindo, Masahiro Nakayama, Ayako Matsuzawa, Akihiro Kobayashi, Honami Ogoh, Toshio Watanabe, Chikashi Ishioka, Natsuko Chiba

    Molecular cancer research : MCR　16　(10)　1499-1511　2018/10

    DOI： 10.1158/1541-7786.MCR-18-0269 　

    ISSN： 1541-7786

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    BRCA1 functions as a tumor suppressor in DNA repair and centrosome regulation. Previously, Obg-like ATPase 1 (OLA1) was shown to interact with BARD1, a heterodimer partner of BRCA1. OLA1 binds to BRCA1, BARD1, and γ-tubulin and functions in centrosome regulation. This study determined that overexpression of wild-type OLA1 (OLA1-WT) caused centrosome amplification due to centriole overduplication in mammary tissue-derived cells. Centrosome amplification induced by overexpression of the cancer-derived OLA1 mutant, which is deficient at regulating centrosome number, occurred in significantly fewer cells than in that induced by overexpression of OLA1-WT. Thus, it was hypothesized that overexpression of OLA1 with normal function efficiently induces centrosome amplification, but not that of OLA1 mutants, which are deficient at regulating centrosome number. We analyzed whether overexpression of OLA1 missense mutants of nine candidate phosphorylation residues, three residues modified with acetylation, and two ATP-binding residues caused centrosome amplification and identified five missense mutants that are deficient in the regulation of centrosome number. Three of them did not bind to BARD1. Two phosphomimetic mutations restored the binding to BARD1 and the efficient centrosome amplification by their overexpression. Knockdown and overexpression of BARD1 also caused centrosome amplification. BARD1 mutant reported in cancer failed to bind to OLA1 and rescue the BARD1 knockdown-induced centrosome amplification and reduced its centrosomal localization. Combined, these data reveal that the OLA1-BARD1 interaction is important for the regulation of centrosome number.Implications: Regulation of centrosome number by BRCA1/BARD1 together with OLA1 is important for the genome integrity to prevent tumor development. Mol Cancer Res; 16(10); 1499-511. ©2018 AACR.

  10. Inhibition of glycogen synthase kinase-3 beta induces apoptosis and mitotic catastrophe by disrupting centrosome regulation in cancer cells. International-journal Peer-reviewed

    Yuki Yoshino, Chikashi Ishioka

    Scientific reports　5　13249-13249　2015/08/21

    DOI： 10.1038/srep13249 　

    ISSN： 2045-2322

  11. BET family BRD3 initiates DSB-induced chromatin remodeling with TIP60 to promote R-loop-mediated HR. International-journal Peer-reviewed

    Jianghao Qian, Tomoko Watanabe, Reiko Watanabe, Shin-Ichiro Kanno, Akiko Takahashi, Shinji Kohsaka, Yuki Yoshino, Natsuko Chiba, Kozo Tanaka, Takashi Kohno, Akira Yasui, Ayako Ui

    Cell reports　44　(11)　116461-116461　2025/10/22

    DOI： 10.1016/j.celrep.2025.116461 　

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    Mechanisms for genome stability in actively transcribed regions are essential for cellular homeostasis; however, these mechanisms are poorly understood. Herein, we identify the bromodomain and extraterminal domain (BET) family BRD3 as the genome caretaker in actively transcribed chromatin. We identify the protein network between BRD3 and chromatin remodeler TIP60. During transcription, BRD3 localizes to actively transcribed chromatin through its N-terminal bromodomains. Following DNA double-strand breaks (DSBs) at the actively transcribed chromatin, the C-terminal extraterminal (ET) domain of BRD3 recruits CHD4 via its KIKL-like motifs to replace HP1 with the TIP60 (Tat-interactive protein, 60 kDa) complex, promoting H4K16 acetylation and MBTD1 recruitment, which creates chromatin barriers to 53BP1. This process recruits BRCA1 and R-loop-processing factors to promote R-loop-mediated homologous recombination (HR) and suppress 53BP1 and mutagenic non-homologous end-joining. Our study elucidates the mechanism by which BRD3 initiates DSB-induced chromatin remodeling by CHD4 and TIP60 to promote R-loop-mediated HR on actively transcribed chromatin to maintain genome stability.

  12. Assay for Site-specific Homologous Recombination Activity in adherent cells, suspension cells, and tumor tissues Peer-reviewed

    Yoshino Y., Kikuta S., Chiba N.

    Bio-protocol　15　(7)　e5260　2025/04

    DOI： 10.21769/BioProtoc.5260 　

  13. Nicaraven enhances the cytotoxicity of X-ray irradiation in cancer cells with homologous recombination deficiency. International-journal Peer-reviewed

    Yuki Yoshino, Kazuko Ichimiya, Keiichi Jingu, Yuhzo Fujita, Natsuko Chiba

    Biochemical and biophysical research communications　742　151153-151153　2025/01

    DOI： 10.1016/j.bbrc.2024.151153 　

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    Poly (ADP-ribose) polymerase (PARP) is involved in the repair of DNA single-strand breaks. PARP inhibitors are cytotoxic to cancer cells with homologous recombination (HR) deficiency through a synthetic lethality mechanism. Nicaraven is a hydroxyl radical scavenger that has been investigated for the treatment of organ ischemia such as brain infarction. Nicaraven also shows PARP inhibitory and anti-cancer activity in vitro and in vivo. In this study, we investigated the potential synthetic lethality of nicaraven in cells with HR deficiency and whether the PARP inhibitory and radical scavenger activities of nicaraven contributes to its anti-cancer effects, especially in combination with exposure to ionizing radiation. The results showed that nicaraven was cytotoxic against cancer cells after knockdown of the HR factors BRCA1 or RAD51, indicating that nicaraven exerted synthetic lethal effects on cells with HR deficiency. X-ray irradiation-induced DNA double-strand breaks (DSBs) increased at 2 h and were largely repaired after 24 h in control cells, whereas nicaraven significantly increased the amounts of residual DSBs 24 h after X-ray irradiation, especially in HR-deficient cells. Nicaraven treatment enhanced the cytotoxicity of X-ray irradiation in HR-deficient cells, but not that in HR-proficient cells. These data suggest that the combination of nicaraven with X-ray irradiation selectively increases the cytotoxic effects of X-ray irradiation on HR-deficient cancer cells. Thus, nicaraven might be a valuable agent for cancer therapy, particularly in combination with radiotherapy.

  14. Protocol to detect OLA1 polyubiquitination by Aurora A in vivo and in vitro. International-journal Peer-reviewed

    Zhenzhou Fang, Xingming Li, Yuki Yoshino, Natsuko Chiba

    STAR protocols　5　(2)　103008-103008　2024/04/10

    DOI： 10.1016/j.xpro.2024.103008 　

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    Aurora A is a critical kinase that functions in centrosome maturation and bipolar spindle assembly. On the other hand, Aurora A has E3 ubiquitin ligase activity and polyubiquitinates Breast cancer gene 1 (BRCA1)-interacting protein Obg-like ATPase 1 (OLA1), targeting it for proteasomal degradation. Here, we present a protocol to detect OLA1 ubiquitination. We describe steps for recovering frozen cells and protein purification. We then detail assays for both in vivo and in vitro ubiquitination of OLA1 by Aurora A. For complete details on the use and execution of this protocol, please refer to Fang et al.1.

  15. The centrosome: a critical hub for cell cycle regulation Invited

    Yuki Yoshino, Zhenzhou Fang, Natsuko Chiba

    Trends in Cell Biology　2024/04

    Publisher: Elsevier BV

    DOI： 10.1016/j.tcb.2024.04.003 　

    ISSN： 0962-8924

  16. Bevacizumab increases the sensitivity of olaparib to homologous recombination-proficient ovarian cancer by suppressing CRY1 via PI3K/AKT pathway

    Yoshino Yuki

    FRONTIERS IN ONCOLOGY　2024

    DOI： 10.3389/FONC.2024.1302850 　

  17. Paclitaxel sensitizes homologous recombination-proficient ovarian cancer cells to PARP inhibitor via the CDK1/BRCA1 pathway. International-journal Peer-reviewed

    Nozomu Yanaihara, Yuki Yoshino, Daito Noguchi, Junya Tabata, Masataka Takenaka, Yasushi Iida, Misato Saito, Satoshi Yanagida, Masami Iwamoto, Takako Kiyokawa, Natsuko Chiba, Aikou Okamoto

    Gynecologic oncology　168　83-91　2023/01

    DOI： 10.1016/j.ygyno.2022.11.006 　

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    OBJECTIVE: An effective treatment strategy for epithelial ovarian cancer (EOC) with homologous recombination (HR)-proficient (HRP) phenotype has not been established, although poly (ADP-ribose) polymerase inhibitors (PARPi) impact the disease course with HR-deficient (HRD) phenotype. Here, we aimed to clarify the cellular effects of paclitaxel (PTX) on the DNA damage response and the therapeutic application of PTX with PARPi in HRP ovarian cancer. METHODS: Two models with different PTX dosing schedules were established in HRP ovarian cancer OVISE cells. Growth inhibition and HR activity were analyzed in these models with or without PARPi. BRCA1 phosphorylation status was examined in OVISE cells by inhibiting CDK1, which was reduced by PTX treatment. CDK1 expression was evaluated in EOC patients treated with PTX-based neoadjuvant chemotherapy. RESULTS: PTX suppressed CDK1 expression resulting in impaired BRCA1 phosphorylation in OVISE cells. The reduced CDK1 activity by PTX could decrease HR activity in response to DNA damage and therefore increase the sensitivity to PARPi. Immunohistochemistry showed that CDK1 expression was attenuated in samples collected after PTX-based chemotherapy compared to those collected before chemotherapy. The decrease in CDK1 expression was greater with dose-dense PTX schedule than with the conventional PTX schedule. CONCULSIONS: PTX could act synergistically with PARPi in HRP ovarian cancer cells, suggesting that the combination of PTX with PARPi may be a novel treatment strategy extending the utility of PARPi to EOC. Our findings provide cules for future translational clinical trials evaluating the efficacy of PTX in combination with PARPi in HRP ovarian cancer.

  18. Roles of RACK1 in centrosome regulation and carcinogenesis. International-journal Invited Peer-reviewed

    Yuki Yoshino, Natsuko Chiba

    Cellular signalling　90　110207-110207　2022/02

    DOI： 10.1016/j.cellsig.2021.110207 　

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    Receptor for activated C kinase 1 (RACK1) regulates various cellular functions and signaling pathways by interacting with different proteins. Recently, we showed that RACK1 interacts with breast cancer gene 1 (BRCA1), which regulates centrosome duplication. RACK1 localizes to centrosomes and spindle poles and is involved in the proper centrosomal localization of BRCA1. The interaction between RACK1 and BRCA1 is critical for the regulation of centrosome number. In addition, RACK1 contributes to centriole duplication by regulating polo-like kinase 1 (PLK1) activity in S phase. RACK1 binds directly to PLK1 and Aurora A, promoting the phosphorylation of PLK1 and activating the Aurora A/PLK1 signaling axis. Overexpression of RACK1 causes centrosome amplification, especially in mammary gland epithelial cells, inducing overactivation of PLK1 followed by premature centriole disengagement and centriole re-duplication. Other proteins, including hypoxia-inducible factor α, von Hippel-Lindau protein, heat-shock protein 90, β-catenin, and glycogen synthase kinase-3β, interact with RACK1 and play roles in centrosome regulation. In this review, we focus on the roles and underlying molecular mechanisms of RACK1 in centrosome regulation mediated by its interaction with different proteins and the modulation of their functions.

  19. Dysregulation of the centrosome induced by BRCA1 deficiency contributes to tissue‐specific carcinogenesis International-journal Peer-reviewed

    Yuki Yoshino, Zhenzhou Fang, Huicheng Qi, Akihiro Kobayashi, Natsuko Chiba

    Cancer Science　112　(5)　1679-1687　2021/05

    Publisher: Wiley

    DOI： 10.1111/cas.14859 　

    ISSN： 1347-9032

    eISSN： 1349-7006

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    Alterations in breast cancer gene 1 (BRCA1), a tumor suppressor gene, increase the risk of breast and ovarian cancers. BRCA1 forms a heterodimer with BRCA1-associated RING domain protein 1 (BARD1) and functions in multiple cellular processes, including DNA repair and centrosome regulation. BRCA1 acts as a tumor suppressor by promoting homologous recombination (HR) repair, and alterations in BRCA1 cause HR deficiency, not only in breast and ovarian tissues but also in other tissues. The molecular mechanisms underlying BRCA1 alteration-induced carcinogenesis remain unclear. Centrosomes are the major microtubule-organizing centers and function in bipolar spindle formation. The regulation of centrosome number is critical for chromosome segregation in mitosis, which maintains genomic stability. BRCA1/BARD1 function in centrosome regulation together with Obg-like ATPase (OLA1) and receptor for activating protein C kinase 1 (RACK1). Cancer-derived variants of BRCA1, BARD1, OLA1, and RACK1 do not interact, and aberrant expression of these proteins results in abnormal centrosome duplication in mammary-derived cells, and rarely in other cell types. RACK1 is involved in centriole duplication in the S phase by promoting polo-like kinase 1 activation by Aurora A, which is critical for centrosome duplication. Centriole number is higher in cells derived from mammary tissues compared with in those derived from other tissues, suggesting that tissue-specific centrosome characterization may shed light on the tissue specificity of BRCA1-associated carcinogenesis. Here, we explored the role of the BRCA1-containing complex in centrosome regulation and the effect of its deficiency on tissue-specific carcinogenesis.

  20. The Function of BARD1 in Centrosome Regulation in Cooperation with BRCA1/OLA1/RACK1. International-journal Peer-reviewed

    Kei Otsuka, Yuki Yoshino, Huicheng Qi, Natsuko Chiba

    Genes　11　(8)　2020/07/24

    DOI： 10.3390/genes11080842 　

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    Breast cancer gene 1 (BRCA1)-associated RING domain protein 1 (BARD1) forms a heterodimer with BRCA1, a tumor suppressor associated with hereditary breast and ovarian cancer. BRCA1/BARD1 functions in multiple cellular processes including DNA repair and centrosome regulation. Centrosomes are the major microtubule-organizing centers in animal cells and are critical for the formation of a bipolar mitotic spindle. BRCA1 and BARD1 localize to the centrosome during the cell cycle, and the BRCA1/BARD1 dimer ubiquitinates centrosomal proteins to regulate centrosome function. We identified Obg-like ATPase 1 (OLA1) and receptor for activated C kinase (RACK1) as BRCA1/BARD1-interating proteins that bind to BARD1 and BRCA1 and localize the centrosomes during the cell cycle. Cancer-derived variants of BRCA1, BARD1, OLA1, and RACK1 failed to interact, and aberrant expression of these proteins caused centrosome amplification due to centriole overduplication only in mammary tissue-derived cells. In S-G2 phase, the number of centrioles was higher in mammary tissue-derived cells than in cells from other tissues, suggesting their involvement in tissue-specific carcinogenesis by BRCA1 and BARD1 germline mutations. We described the function of BARD1 in centrosome regulation in cooperation with BRCA1/OLA1/RACK1, as well as the effect of their dysfunction on carcinogenesis.

  21. First person - Yuki Yoshino

    Yoshino Yuki

    JOURNAL OF CELL SCIENCE　2020

    DOI： 10.1242/JCS.253153 　

  22. 抗がん剤感受性を予測するDNA修復能の測定法の開発 Invited

    吉野 優樹, 遠藤栞乃, 千葉奈津子

    化学工業　70　(10)　709-715　2019/10

  23. microRNA-193a-3p is specifically down-regulated and acts as a tumor suppressor in BRAF-mutated colorectal cancer. International-journal Peer-reviewed

    Hidekazu Takahashi, Masanobu Takahashi, Shinobu Ohnuma, Michiaki Unno, Yuki Yoshino, Kota Ouchi, Shin Takahashi, Yasuhide Yamada, Hideki Shimodaira, Chikashi Ishioka

    BMC cancer　17　(1)　723-723　2017/11/07

    DOI： 10.1186/s12885-017-3739-x 　

    ISSN： 1471-2407

    eISSN： 1471-2407

  24. OLA1 gene sequencing in patients with BRCA1/2 mutation-negative suspected hereditary breast and ovarian cancer. Peer-reviewed

    Masanobu Takahashi, Natsuko Chiba, Hideki Shimodaira, Yuki Yoshino, Takahiro Mori, Makiko Sumii, Tadashi Nomizu, Chikashi Ishioka

    Breast cancer (Tokyo, Japan)　24　(2)　336-340　2017/03

    DOI： 10.1007/s12282-016-0709-0 　

    ISSN： 1340-6868

    eISSN： 1880-4233

  25. Regulation of the centrosome cycle. International-journal Peer-reviewed

    Hiroki Fujita, Yuki Yoshino, Natsuko Chiba

    Molecular & cellular oncology　3　(2)　e1075643　2016/03

    DOI： 10.1080/23723556.2015.1075643 　

    More details Close

    The centrosome, consisting of mother and daughter centrioles surrounded by the pericentriolar matrix (PCM), functions primarily as a microtubule organizing center (MTOC) in most animal cells. In dividing cells the centrosome duplicates once per cell cycle and its number and structure are highly regulated during each cell cycle to organize an effective bipolar spindle in the mitotic phase. Defects in the regulation of centrosome duplication lead to a variety of human diseases, including cancer, through abnormal cell division and inappropriate chromosome segregation. At the end of mitosis the daughter centriole disengages from the mother centriole. This centriole disengagement is an important licensing step for centrosome duplication. In S phase, one new daughter centriole forms perpendicular to each centriole. The centrosome recruits further PCM proteins in the late G2 phase and the two centrosomes separate at mitotic entry to form a bipolar spindle. Here, we summarize research findings in the field of centrosome biology, focusing on the mechanisms of regulation of the centrosome cycle in human cells.

  26. A Curcumin Analog, GO-Y078, Effectively Inhibits Angiogenesis through Actin Disorganization. International-journal Peer-reviewed

    Shunsuke Sugiyama, Yuki Yoshino, Sei Kuriyama, Masahiro Inoue, Keigo Komine, Kazunori Otsuka, Aki Kohyama, Hiroyuki Yamakoshi, Chikashi Ishioka, Masamitsu Tanaka, Yoshiharu Iwabuchi, Hiroyuki Shibata

    Anti-cancer agents in medicinal chemistry　16　(5)　633-47　2016

    DOI： 10.2174/1871520615666151013125559 　

    ISSN： 1871-5206

    eISSN： 1875-5992

  27. Inhibition of invasion by glycogen synthase kinase-3 beta inhibitors through dysregulation of actin re-organisation via down-regulation of WAVE2. International-journal Peer-reviewed

    Yuki Yoshino, Manami Suzuki, Hidekazu Takahashi, Chikashi Ishioka

    Biochemical and biophysical research communications　464　(1)　275-80　2015/08/14

    DOI： 10.1016/j.bbrc.2015.06.142 　

    ISSN： 0006-291X

    eISSN： 1090-2104

  28. 分子標的薬の耐性機序 Invited

    吉野 優樹, 石岡千加史

    がん分子標的治療　12　(2)　122-128　2014/06

  29. 転移性肺腫瘍に対する分子標的治療・消化器癌 Invited

    吉野 優樹, 石岡千加史

    日本胸部臨床　73　(2)　146-164　2014/02

  30. Acute exacerbation of paraneoplastic neurological syndrome after massive tumor lysis of neuroendocrine carcinoma by chemoradiotherapy Peer-reviewed

    Yoshino Y, Akiyama S, Ouchi K, Oishi T, Takahashi H, Lee J, Takahashi S, Shimodaira H, Kato S, Ishioka C

    International Cancer Conference Journal　2　(4)　247-250　2013/10

    DOI： 10.1007/s13691-013-0100-3 　

  31. 分子標的治療薬の進歩 ~特徴と将来の展望~ Invited

    吉野 優樹, 石岡千加史

    耳鼻咽喉科・頭頸部外科　85　(7)　472-478　2013/06

  32. S100A4, frequently overexpressed in various human cancers, accelerates cell motility in pancreatic cancer cells. International-journal Peer-reviewed

    Hitoshi Sekine, Na Chen, Keisuke Sato, Yuriko Saiki, Yuki Yoshino, Yukiko Umetsu, Guo Jin, Hiroki Nagase, Zhaodi Gu, Shinichi Fukushige, Makoto Sunamura, Akira Horii

    Biochemical and biophysical research communications　429　(3-4)　214-9　2012/12/14

    DOI： 10.1016/j.bbrc.2012.10.048 　

    ISSN： 0006-291X

  33. DCK is frequently inactivated in acquired gemcitabine-resistant human cancer cells. International-journal Peer-reviewed

    Yuriko Saiki, Yuki Yoshino, Hiroko Fujimura, Tatsuya Manabe, Yuki Kudo, Miki Shimada, Nariyasu Mano, Tomohiro Nakano, Yoonha Lee, Shinjiro Shimizu, Shinya Oba, Sho Fujiwara, Hideyuki Shimizu, Na Chen, Zhaleh Kashkouli Nezhad, Guo Jin, Shinichi Fukushige, Makoto Sunamura, Masaharu Ishida, Fuyuhiko Motoi, Shinichi Egawa, Michiaki Unno, Akira Horii

    Biochemical and biophysical research communications　421　(1)　98-104　2012/04/27

    DOI： 10.1016/j.bbrc.2012.03.122 　

    ISSN： 0006-291X

  34. A new 10-min ligation method using a modified buffer system with a very low amount of T4 DNA ligase: the "Coffee Break Ligation" technique. International-journal Peer-reviewed

    Yuki Yoshino, Masaharu Ishida, Akira Horii

    Biotechnology letters　29　(10)　1557-60　2007/10

    DOI： 10.1007/s10529-007-9429-z 　

    ISSN： 0141-5492

Show all ︎Show first 5

Misc. 49

  1. Aurora A has a dual function in polyubiquitination of BRCA1-interacting protein OLA1 to promote centrosome maturation

    Yoshino Yuki

    CANCER SCIENCE　2025

  2. An assay for evaluation of homologous recombination activity in tumor tissues to predict sensitivity to PARP inhibitors

    Yoshino Yuki

    CANCER SCIENCE　2025

  3. BRCA1-binding factor deficiency induces tumorigenesis dependent on estrogen-regulated centrosome amplification

    Natsuko Chiba, Honami Ogoh, Yudai Iichi, Tomohiro Sasaki, Takahiro Yoshida, Shiori Ichimura, Zhenzhou Fang, Xingming Li, Mitsuru Futakuchi, Yasuhiro Nakamura, Toshio Watanabe, Yuki Yoshino

    CANCER SCIENCE　116　1275-1275　2025/01

    ISSN： 1347-9032

    eISSN： 1349-7006

  4. PP1AはAurora AによるOLA1のユビキチン化を亢進して中心体成熟を促進する(PP1A increases the OLA1 polyubiquitination by Aurora A to promote centrosome maturation)

    李 星明, 方 震宙, 太谷 凜, 渡邉 みのり, 諸岡 麻衣, 吉野 優樹, 森 隆弘, 千葉 奈津子, 千葉 奈津子

    日本癌学会総会記事　83回　P-1061　2024/09

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  5. がんの進展とともに加速するゲノム不安定性 BRCA1結合分子の欠損はエストロゲンで制御される中心体増幅に依存した悪性化を示す腫瘍を誘導する(Genomic instability: a cogwheel promoting cancer development and progression BRCA1-binding factor deficiency induces tumorigenesis dependent on estrogen-regulated centrosome amplification)

    千葉 奈津子, 小河 穂波, 飯地 雄大, 佐々木 伯大, 吉田 貴大, 市村 志織, 方 震宙, 李 星明, 二口 充, 中村 保宏, 渡邊 利雄, 吉野 優樹

    日本癌学会総会記事　83回　S15-3　2024/09

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  6. The direct evaluation of homologous recombination activity in tissues to predict the risk of hereditary breast and ovarian cancer and the sensitivity to PARP inhibitor

    Yoshino Yuki

    EUROPEAN JOURNAL OF CANCER　2024

    DOI： 10.1016/J.EJCA.2024.114714 　

  7. BRCA1-interacting protein OLA1 promotes DNA damage-induced centrosome amplification through the activation of PLK1

    Yoshino Yuki

    CANCER SCIENCE　2024

  8. BARD1 suppresses the OLA1 polyubiquitination by Aurora A to regulate centrosome maturation

    Yoshino Yuki

    CANCER SCIENCE　2024

  9. BRCA1-associated protein RACK1 regulates centrosome duplication in breast cancer cells

    Yoshino Yuki

    CANCER SCIENCE　2024

  10. BRCA1-binding factor deficiency induces tumorigenesis dependent on estrogen-regulated centrosome amplification

    千葉奈津子, 小河穂波, 飯地雄大, 佐々木伯大, 吉田貴大, 市村志織, 方震宙, 李星明, 二口充, 中村保宏, 渡邊利雄, 吉野優樹

    日本癌学会学術総会抄録集(Web)　83rd　2024

  11. Development of a method to directly evaluate homologous recombination activity in cancer tissues

    Yoshino Yuki

    CANCER SCIENCE　2023

  12. BRCA1 is involved in the ubiquitination of OLA1 by Aurora A to promote centrosome maturation

    Yoshino Yuki

    CANCER SCIENCE　2023

  13. NEK2 regulates centrosome number through promoting OLA1 ubiquitination by Aurora A

    Yoshino Yuki

    CANCER SCIENCE　2023

  14. Effects of functional changes in hereditary breast cancer gene products on carcinogenesis and drug resistance

    Yoshino Yuki

    CANCER SCIENCE　2023

  15. Alteration of BRCA1-asscociated proteins causes centrosome aberration resulting in genome instability

    Yoshino Yuki

    CANCER SCIENCE　2023

  16. BRCA1 transports DNA-damaging signal to centrosome through its phosphorylation by ATM

    Natsuko Chiba, Megumi Kikuchi, Zhenzhou Fang, Takato Goto, Yuki Yoshino, Chikashi Ishioka, Huicheng Qi

    CANCER SCIENCE　113　2022/02

    ISSN： 1347-9032

    eISSN： 1349-7006

  17. Regulatory mechanism of precise localization of BRCA1 in centrosome

    Yoshino Yuki

    CANCER SCIENCE　2022

  18. Transcriptional activation by BRCA1/ATF1 contributes to resistance to Olaparib.

    Yoshino Yuki

    CANCER SCIENCE　2022

  19. Aurora A-dependent ubiquitination of OLA1 regulates centrosome number via controlling the recruitment of PCM proteins

    Yoshino Yuki

    CANCER SCIENCE　2022

  20. 患者層別化のためのがん組織におけるDNA損傷修復活性測定法の開発

    吉野優樹

    中谷医工計測技術振興財団年報　(35)　2022

    ISSN： 0914-2487

  21. BRCA1のリン酸化の時空間的動態の解析

    吉野優樹

    上原記念生命科学財団研究報告集(CD-ROM)　36　2022

    ISSN： 2433-3441

  22. Dual activities of Aurora A regulate OLA1 ubiquitination to control centrosome number

    Yoshino Yuki

    CANCER SCIENCE　2021

  23. BRCA1-interacting transcription factor ATF1 is involved in novel mechanism of olaparib resistance

    Yoshino Yuki

    CANCER SCIENCE　2021

  24. Phosphorylated BRCA1 contributes DNA damage-induced centrosome amplification via centrosomal localization of Aurora A

    Yoshino Yuki

    CANCER SCIENCE　2021

  25. Acetylsalicylic acid suppresses centrosome amplification induced by BRCA1 deficiency

    Yoshino Yuki

    CANCER SCIENCE　2021

  26. Functional Analysis of a Tumor Suppressor Gene, BRCA1

    吉野優樹

    東北医学雑誌　133　(1)　2021

    ISSN： 0040-8700

  27. Over-expression of BRCA1-interacting protein BIP2 causes centrosome amplification by activating PLK1 and Aurora A.

    Yoshino Yuki

    CANCER SCIENCE　2018

  28. BRCA1-interacting protein OLA1 regulates centrosome amplification induced by DNA damage

    Yoshino Yuki

    CANCER SCIENCE　2018

  29. BRCA1 suppresses centrosome amplification induced by BIP2 over-expression in mammary epithelial cells

    Yoshino Yuki

    CANCER SCIENCE　2018

  30. A novel CRISPR-based assay can evaluate homologous recombination activity of BRCA1 mutants more accurately

    Yoshino Yuki

    CANCER SCIENCE　2018

  31. 新規乳がん関連分子のがんの診断・治療のバイオマーカーとしての有用性の検討

    千葉奈津子, 吉野優樹

    大和証券ヘルス財団研究業績集　40　2017

  32. 中心体制御因子としての新規BRCA1結合因子BIP2の同定

    吉野 優樹, 齋 匯成, 石岡 千加史, 安井 明, 千葉 奈津子

    日本癌学会総会記事　75回　P-3034　2016/10

    Publisher: 日本癌学会

    ISSN： 0546-0476

  33. 新規中心体タンパク質BIP2はBRCA1の中心体局在と発がん機構に関与する

    齋 匯成, 吉野 優樹, 石岡 千加史, 千葉 奈津子

    日本癌学会総会記事　75回　P-3033　2016/10

    Publisher: 日本癌学会

    ISSN： 0546-0476

  34. 中心体制御因子としての新規BRCA1結合因子BIP2の同定

    吉野 優樹, 齋 匯成, 石岡 千加史, 安井 明, 千葉 奈津子

    日本癌学会総会記事　75回　P-3034　2016/10

    Publisher: 日本癌学会

    ISSN： 0546-0476

  35. 新規中心体タンパク質BIP2はBRCA1の中心体局在と発がん機構に関与する

    齋 匯成, 吉野 優樹, 石岡 千加史, 千葉 奈津子

    日本癌学会総会記事　75回　P-3033　2016/10

    Publisher: 日本癌学会

    ISSN： 0546-0476

  36. OLA1とBRCA1/BARD1二量体の協調的な中心体制御と発がん機構

    藤田 拡樹, 吉野 優樹, 阿部 舜, 齋 匯成, 小宮山 裕平, 石岡 千加史, 千葉 奈津子

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　88回・38回　[2LBA059]-[2LBA059]　2015/12

    Publisher: (公社)日本生化学会

  37. Glycogen synthase kinase-3β阻害薬による中心体異常と分裂期細胞死の誘導

    吉野 優樹, 千葉 奈津子, 石岡 千加史

    日本癌学会総会記事　74回　J-1086　2015/10

    Publisher: 日本癌学会

    ISSN： 0546-0476

  38. OLA1はBRCA1、BARD1とともに中心体数を制御する

    藤田 拡樹, 吉野 優樹, 石岡 千加史, 千葉 奈津子

    日本癌学会総会記事　74回　P-1171　2015/10

    Publisher: 日本癌学会

    ISSN： 0546-0476

  39. 進行再発大腸癌14例に対するレゴラフェニブの有効性と安全性に関する後方視的検討

    大石 隆之, 高橋 雅信, 吉野 優樹, 李 仁, 塩野 雅俊, 高橋 昌宏, 城田 英和, 下平 秀樹, 加藤 俊介, 石岡 千加史

    日本癌治療学会誌　49　(3)　2417-2417　2014/06

    Publisher: (一社)日本癌治療学会

    ISSN： 0021-4671

  40. Molecular targeted agents for gastrointestinal malignancies

    Yuki Yoshino, Chikashi Ishioka

    Japanese Journal of Chest Diseases　73　(2)　146-164　2014/02/01

    Publisher: 克誠堂出版

    ISSN： 0385-3667

  41. 標準治療抵抗性の進行再発大腸癌14例に対するレゴラフェニブの効果と安全性に関する後ろ向き検討

    大石隆之, 高橋雅信, 吉野優樹, LEE Jin, 塩野雅俊, 高橋昌宏, 城田英和, 下平秀樹, 加藤俊介, 石岡千加史

    日本臨床腫瘍学会学術集会(CD-ROM)　12th　2014

  42. 新規クルクミン類縁体を用いた血管新生抑制効果の検討(Anti-angiogenic potential of newly synthesized curcumin analog)

    杉山 俊輔, 吉野 優樹, 田中 正光, 栗山 正, 岩渕 好治, 石岡 千加史, 柴田 浩行

    日本癌学会総会記事　72回　315-315　2013/10

    Publisher: 日本癌学会

    ISSN： 0546-0476

  43. Progress in development of molecular targeted drugs, its characteristics and perspectives

    Yuki Yoshino, Chikashi Ishioka

    Otolaryngology - Head and Neck Surgery (Japan)　85　472-478　2013/07/01

    ISSN： 0914-3491

  44. 神経線維腫症1型に併発した悪性末梢神経鞘腫瘍に対し化学療法を行った3例

    下平 秀樹, 西條 憲, 大内 康太, 高橋 秀和, 吉野 優樹, 李 仁, 佐藤 悠子, 塩野 雅俊, 加藤 俊介, 石岡 千加史

    日本内科学会雑誌　102　(Suppl.)　243-243　2013/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

  45. がん治療における腫瘍内科医による上腕CVポート留置術の有用性 約600症例での検討を基に

    塩野 雅俊, 高橋 信, 角道 祐一, 高橋 雅信, 坂本 康寛, 添田 大司, 吉野 優樹, 下平 秀樹, 加藤 俊介, 石岡 千加史

    日本内科学会雑誌　102　(Suppl.)　283-283　2013/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

  46. ゲムシタビン耐性ヒト癌細胞株におけるdeoxycytidine kinaseの不活化(Deoxycytidine kinase is frequently inactivated in acquired gemcitabine-resistant human cancer cells)

    齋木 由利子, 吉野 優樹, 福重 真一, 砂村 真琴, 石田 晶玄, 元井 冬彦, 江川 新一, 海野 倫明, 堀井 明

    日本癌学会総会記事　71回　237-237　2012/08

    Publisher: 日本癌学会

    ISSN： 0546-0476

  47. Clinical outcome of recombinant human soluble thrombomodulin (rTM) for patients with disseminated intravascular coagulation (DIC) complicating advanced solid cancer: Retrospective analysis Peer-reviewed

    Shin Takahashi, Kohta Ohuchi, Shunsuke Kato, Hideki Shimodaira, Yuichi Kakudo, Shoko Akiyama, Kozue Yoshida, Masatoshi Shiono, Yoshinari Okada, Shunsuke Sugiyama, Naoko Saito, Jin Lee, Takayuki Oishi, Hidekazu Takahashi, Yuki Yoshino, Chikashi Ishioka

    JOURNAL OF CLINICAL ONCOLOGY　30　(15)　2012/05

    ISSN： 0732-183X

    eISSN： 1527-7755

  48. 進行・再発悪性腫瘍に対する塩酸イリノテカンを含む薬物療法におけるUGT1A1遺伝子多型と有害事象発現との関連に対する後方視的検討

    李 仁, 秋山 聖子, 吉野 優樹, 大石 隆之, 齋藤 菜穂子, 高橋 秀和, 加藤 俊介, 角道 祐一, 下平 秀樹, 石岡 千加史

    日本内科学会雑誌　101　(Suppl.)　259-259　2012/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

  49. 進行再発大腸癌においてセツキシマブ不応後にパニツムマブを施行した治療成績

    李 仁, 加藤 俊介, 高橋 昌宏, 高橋 秀和, 大内 康太, 吉野 優樹, 大石 隆之, 斎藤 菜穂子, 杉山 俊輔, 岡田 佳也, 小峰 啓吾, 西條 憲, 河合 貞幸, 井上 正広, 今井 源, 塩野 雅俊, 吉田 こず恵, 秋山 聖子, 高橋 信, 角道 祐一, 下平 秀樹, 森 隆弘, 石岡 千加史

    東北医学雑誌　123　(2)　210-210　2011/12

    Publisher: 東北医学会

    ISSN： 0040-8700

Show all ︎Show first 5

Books and Other Publications 1

  1. インフォームドコンセントのための図説シリーズ 抗悪性腫瘍薬-分子標的治療薬-改訂版

    吉野 優樹, 千葉奈津子

    医薬ジャーナル社　2015

Presentations 79

  1. 治療感受性予測のための腫瘍組織の相同組み換え活性測定法開発の基礎研究

    本成登貴和, 吉野優樹, 佐藤未来, 宮下穣, 濱中洋平, 江幡明子, 原田成美, 多田寛, 千葉奈津子, 石田孝宣

    日本外科学会定期学術集会(Web)　2024

  2. 乳癌発症リスク評価/治療効果予測を目指した臨床検体の相同組み換え修復活性評価法開発の基礎的検討

    本成 登貴和, 吉野 優樹, 春田 萌, 宮下 穣, 濱中 洋平, 江幡 明子, 原田 成美, 多田 寛, 千葉 奈津子, 石田 孝宣

    日本乳癌学会総会プログラム抄録集　2023/06

  3. BARD1 suppresses the OLA1 polyubiquitination by Aurora A to regulate centrosome maturation

    李星明, 方震宙, 室岡妃南里, 渡邉みのり, 吉野優樹, 森隆弘, 千葉奈津子

    日本癌学会学術総会抄録集(Web)　2023

  4. BRCA1-interacting protein OLA1 promotes DNA damage-induced centrosome amplification through the activation of PLK1

    方震宙, 小林利咲, 蕭澤欽, 吉野優樹, 斉匯成, 千葉奈津子

    日本癌学会学術総会抄録集(Web)　2023

  5. BRCA1-associated protein RACK1 regulates centrosome duplication in breast cancer cells

    吉野優樹, 方震宙, 千葉奈津子

    日本癌学会学術総会抄録集(Web)　2023

  6. がんにおけるゲノム不安定性 BRCA1とその関連分子の変化による中心体制御異常とゲノム不安定性(Alteration of BRCA1-asscociated proteins causes centrosome aberration resulting in genome instability)

    千葉 奈津子, 吉野 優樹, 方 震宙

    日本癌学会総会記事　2022/09

  7. NEK2はAurora AによるOLA1のユビキチン化を促進して中心体数を制御する(NEK2 regulates centrosome number through promoting OLA1 ubiquitination by Aurora A)

    方 震宙, 李 星明, 吉野 優樹, 石岡 千加史, 森 隆弘, 千葉 奈津子

    日本癌学会総会記事　2022/09

  8. BRCA1はAurora AによるOLA1のユビキチン化に作用して中心体成熟を促進する(BRCA1 is involved in the ubiquitination of OLA1 by Aurora A to promote centrosome maturation)

    李 星明, 方 震宙, 吉野 優樹, 石岡 千加史, 森 隆弘, 千葉 奈津子

    日本癌学会総会記事　2022/09

  9. 臨床検体での相同組み換え修復活性評価を目指したDNA二本鎖切断定量法の開発

    本成 登貴和, 吉野 優樹, 角掛 聡子, 進藤 晴彦, 小坂 真吉, 柳垣 美歌, 宮下 穣, 濱中 洋平, 江幡 明子, 原田 成美, 多田 寛, 千葉 奈津子, 石田 孝宣

    日本乳癌学会総会プログラム抄録集　2022/06

  10. BRCA1 transports DNA-damaging signal to centrosome through its phosphorylation by ATM

    Natsuko Chiba, Megumi Kikuchi, Zhenzhou Fang, Takato Goto, Yuki Yoshino, Chikashi Ishioka, Huicheng Qi

    CANCER SCIENCE　2022/02

  11. Aurora A-dependent ubiquitination of OLA1 regulates centrosome number via controlling the recruitment of PCM proteins

    Zhenzhou Fang, Xingming Li, Moe Suzuki, Yuki Yoshino, Huicheng Qi, Takahiro Mori, Natsuko Chiba

    CANCER SCIENCE　2022/02

  12. Alteration of BRCA1-asscociated proteins causes centrosome aberration resulting in genome instability

    千葉奈津子, 吉野優樹, 方震宙

    日本癌学会学術総会抄録集(Web)　2022

  13. BRCA1 is involved in the ubiquitination of OLA1 by Aurora A to promote centrosome maturation

    李星明, 方震宙, 吉野優樹, 石岡千加史, 石岡千加史, 石岡千加史, 森隆弘, 千葉奈津子

    日本癌学会学術総会抄録集(Web)　2022

  14. NEK2 regulates centrosome number through promoting OLA1 ubiquitination by Aurora A

    方震宙, 李星明, 吉野優樹, 石岡千加史, 石岡千加史, 石岡千加史, 森隆弘, 千葉奈津子

    日本癌学会学術総会抄録集(Web)　2022

  15. Effects of functional changes in hereditary breast cancer gene products on carcinogenesis and drug resistance Invited

    吉野優樹, 遠藤栞乃, 千葉奈津子

    日本癌学会学術総会抄録集(Web)　2022

  16. Development of a method to directly evaluate homologous recombination activity in cancer tissues

    遠藤栞乃, 吉野優樹, 千葉奈津子

    日本癌学会学術総会抄録集(Web)　2022

  17. BRCA1はATMによるリン酸化を介してDNA損傷シグナルを中心体に輸送する

    千葉 奈津子, 菊地 めぐみ, 方 震宙, 後藤 孝太, 吉野 優樹, 石岡 千加史, 斉 匯成

    日本癌学会総会記事　2021/09

  18. Aurora AによるOLA1のユビキチン化はPCMを制御して中心体数をコントロールする

    方 震宙, 李 星明, 鈴木 萌, 吉野 優樹, 斉 匯成, 森 隆弘, 千葉 奈津子

    日本癌学会総会記事　2021/09

  19. Dual activities of Aurora A regulate OLA1 ubiquitination to control centrosome number

    Zhenzhou Fang, Yuki Yoshino, Takahiro Mori, Moe Suzuki, Xingming Li, Huicheng Qi, Chikashi Ishioka, Natsuko Chiba

    CANCER SCIENCE　2021/02

  20. Phosphorylated BRCA1 contributes DNA damage-induced centrosome amplification via centrosomal localization of Aurora A

    Huicheng Qi, Yuki Yoshino, Megumi Kikuchi, Zhenzhou Fang, Chikashi Ishioka, Natsuko Chiba

    CANCER SCIENCE　2021/02

  21. 中心体におけるBRCA1の局在部位とその制御機構の解析

    吉野優樹, 千葉奈津子

    日本癌学会学術総会抄録集(Web)　2021

  22. BRCA1/ATF1による転写活性化はオラパリブへの耐性化に関与する

    遠藤栞乃, 吉野優樹, 千葉奈津子

    日本癌学会学術総会抄録集(Web)　2021

  23. Investigation and preclinical development on BRCA1 molecular function

    Yuki Yoshino, Shino Endo, Huicheng Qi, Zhenzhou Fang, Natsuko Chiba

    The 15th International Symposium of the Institute Network for Biomedical Sciences　2020/11/05

  24. リン酸化BRCA1はAurora Aの中心体局在を介してDNA損傷後の中心体増幅を制御する

    斉 匯成, 吉野 優樹, 菊地 めぐみ, 方 震宙, 石岡 千加史, 千葉 奈津子

    日本癌学会総会記事　2020/10

  25. アセチルサリチル酸はBRCA1障害に起因する中心体増幅を抑制する

    吉野 優樹, 遠藤 栞乃, 千葉奈津子

    第79回日本癌学会学術総会　2020/10/01

  26. Aurora Aの2つの活性がOLA1のユビキチン化を制御して中心体数をコントロールする

    方震宙, 吉野 優樹, 森 隆弘, 鈴木 萌, 李星明, 斉匯成, 石岡千加史, 千葉奈津子

    79回日本癌学会学術総会　2020/10/01

  27. BRCA1に結合する転写因子ATF1は新たなオラパリブ体制機構に関与する

    遠藤 栞乃, 吉野 優樹, 千葉奈津子

    第79回日本癌学会学術総会　2020/10/01

  28. リン酸化BRCA1はAurora Aの中心体局在を介してDNA損傷後の中心帯増幅を制御する.

    斉匯成, 吉野 優樹, 菊池 めぐみ, 方震宙, 石岡千加史, 千葉奈津子

    第79回日本癌学会学術総会　2020/10/01

  29. BRCA1関連乳がんの 新たな診断法の開発と 発がん機構の解析 Invited

    吉野 優樹, 遠藤 栞乃, 渡部 剛, 千葉奈津子

    第8回HBOCコンソーシアム学術総会　2020/01/26

  30. BRCA1-interacting transcription factor ATF1 is involved in novel mechanism of olaparib resistance

    遠藤栞乃, 吉野優樹, 千葉奈津子

    日本癌学会学術総会抄録集(Web)　2020

  31. BRCA1はDNA損傷後のAurora Aの中心体局在を制御する

    菊池めぐみ, 齋匯成, 趙懿, 方震宙, 吉野優樹, 千葉奈津子

    第３７回染色体ワークショップ・第１８回核ダイナミクス研究会　2019/12/23

  32. BRCA1とその関連分子による中心体のDNA損傷応答機構の解明.

    斉匯成, 菊地めぐみ, 大橋和音, 方震宙, 吉野優樹, 千葉奈津子

    第３７回染色体ワークショップ・第１８回核ダイナミクス研究会　2019/12/23

  33. BARD1アイソフォームの発現は中心体の異常な伸長を引き起こす

    大塚慧, 内山千尋, 吉野優樹, 齋匯成, 千葉奈津子

    第42回分子生物学会学術総会　2019/12/06

  34. A novel assay to evaluate the activity of homologous recombination in cells.

    Shino Endo, Yuki Yoshino, Natsuko Chiba

    The 14th International Symposium of the Institute Network for Biomedical Sciences　2019/10/02

  35. Centrosome regulation by a novel BRCA1 complex: insight into tissue-specific carcinogenesis.

    Yuki Yoshino, Huicheng Qi, Shino Endo, Zhenzhou Fang, Kei Otsuka, Natsuko Chiba

    The 14th International Symposium of the Institute Network for Biomedical Sciences　2019/10/02

  36. 新規BRCA1結合分子であるOLA1とRACK1は中心体複製を制御してゲノム安定性に寄与する

    千葉奈津子, 吉野優樹, 齋匯成, 遠藤栞乃, 方震宙, 石岡千加史, 安井明

    第78回日本癌学会学術総会　2019/09/28

  37. 新規HR活性測定法ASHRAはPARP阻害薬感受性を予測可能である

    遠藤栞乃, 吉野優樹, 千葉奈津子

    第78回日本癌学会学術総会　2019/09/28

  38. A novel BRCA1-interacting protein, RACK1, contributes centriole duplication in mammary cells via regulation of PLK1.

    Yuki Yoshino, Akihiro Kobayashi, Huicheng Qi, Shino Endo, Zhenzhou Fang, Natsuko Chiba

    第78回日本癌学会学術総会　2019/09/27

  39. Aurora AによるOLA1のユビキチン化は中心体複製制御に重要である

    方震宙, 齋匯成, 森隆弘, 吉野優樹, 鈴木萌, 石岡千加史, 千葉奈津子

    第78回日本癌学会学術総会　2019/09/26

  40. 新規BRCA1結合分子RACK1はPLK1の活性制御を介して乳腺細胞における中心小体複製を寄与する(A novel BRCA1-interacting protein, RACK1, contributes centriole duplication in mammary cells via regulation of PLK1)

    吉野 優樹, 小林 輝大, 斉 匯成, 遠藤 栞乃, 方 震宙, 千葉 奈津子

    日本癌学会総会記事　2019/09

  41. Aurora AによるOLA1のユビキチン化は中心体複製制御に重要である(Aurora A-dependent ubiquitination of OLA1 in the regulation of centrosome number)

    方 震宙, 斉 匯成, 森 隆弘, 吉野 優樹, 鈴木 萌, 石岡 千加史, 千葉 奈津子

    日本癌学会総会記事　2019/09

  42. がん研究における女性研究者(第6回) 新規BRCA1結合分子であるOLA1とRACK1は中心体複製を制御してゲノム安定性に寄与する(Women scientists in cancer research Novel BRCA1-interacting Proteins OLA1 and RACK1 regulate centrosome duplication to maintain genome stability)

    千葉 奈津子, 吉野 優樹, 斉 匯成, 遠藤 栞乃, 方 震宙, 石岡 千加史, 安井 明

    日本癌学会総会記事　2019/09

  43. A novel BRCA1-interacting protein, RACK1, contributes centriole duplication in mammary cells via regulation of PLK1

    吉野優樹, 小林輝大, 斉匯成, 遠藤栞乃, 方震宙, 千葉奈津子

    日本癌学会学術総会抄録集(Web)　2019

  44. より正確に相同組換え修復活性を定量できる新規測定法の開発

    遠藤栞乃, 吉野優樹, 千葉奈津子

    第77回日本癌学会学術総会　2018/09/27

  45. BRCA1結合分子BIP2の過剰発現はPLK1とAurora Aの活性化により中心体過剰複製を引き起こす

    小林輝大, 吉野優樹, 千葉奈津子

    第77回日本癌学会学術総会　2018/09/27

  46. 中心体制御における新規BRCA1結合因子OLA1とBARD1の相互作用の重要性

    吉野優樹, 齋匯成, 藤田拡樹, 小林輝大, 千葉奈津子

    第77回日本癌学会学術総会　2018/09/27

  47. BRCA1-interacting protein OLA1 regulates centrosome amplification induced by DNA damage

    Huicheng Qi, Yuki Yoshino, Zhenzhou Fang, Natsuko Chiba

    CANCER SCIENCE　2018/01

  48. DNA損傷後の中心体数の増加のメカニズムの解明

    齋匯成, 大橋和音, 方震宙, 吉野優樹, 千葉奈津子

    第34回染色体ワークショップ　2017/12/21

  49. BRCA1の新規結合分子Ola1のノックアウトマウスの表現型の解析

    吉田貴大, 吉野優樹, 小河 穂波, 佐々木伯大, 渡邊 利雄, 千葉奈津子

    2017年度生命科学系学会合同年次大会　2017/12/07

  50. 新規BRCA1結合分子BIP2とBRCA1のバランスが正常な中心体複製に重要である

    吉野優樹, 小林輝大, 宮西優太郎, 齋匯成, 遠藤栞乃, 新藤一葉, 千葉奈津子

    2017年度生命科学系学会合同年次大会　2017/12/07

  51. BRCA1-interacting protein OLA1 is involved in the centrosomal duplication and response to DNA damage

    Huicheng Qi, Kazune Ohashi, Zhenzhou Fang, Yuki Yoshino, Natsuko Chiba

    The 33rd International Symposium of Radiation Biology Center　2017/12/05

  52. BRCA1-interacting protein OLA1 in centrosomal regulation and carcinogenesis.

    Yuki Yoshino, Huicheng Qi, Natsuko Chiba

    2nd Global Insight Conference on Breast Cancer　2017/11/04

  53. BRCA1結合分子であるOLA1は中心体のDNA損傷応答を制御する

    齋匯成, 吉野優樹, 方震宙, 千葉奈津子

    第76回日本癌学会学術総会　2017/09/28

  54. BRCA1は乳腺上皮細胞においてBIP2の過剰発現による中心体過剰複製を抑制する

    遠藤栞乃, 吉野優樹, 小林輝大, 齋匯成, 千葉奈津子

    第76回日本癌学会学術総会　2017/09/28

  55. 新規中心体制御因子RACK1によるBRCA1中心体局在制御と発がん

    吉野優樹, 小林輝大, 菅股眞美, 早坂美月, 齋匯成, 千葉奈津子

    第69回日本細胞生物学会大会　2017/06/15

  56. BRCA1結合分子OLA1による中心体のDNA損傷応答機構の解明

    齋匯成, 吉野優樹, 方震宙, 千葉奈津子

    第69回日本細胞生物学会大会　2017/06/13

  57. 新規中心体制御因子RACK1によるBRCA1中心体局在制御と発がん

    吉野 優樹, 小林 輝大, 菅股 眞美, 早坂 美月, 斉 匯成, 千葉 奈津子

    日本細胞生物学会大会講演要旨集　2017/05

  58. BRCA1結合分子OLA1による中心体のDNA損傷応答機構の解明

    斉 匯成, 吉野 優樹, 方 震宙, 千葉 奈津子

    日本細胞生物学会大会講演要旨集　2017/05

  59. 新規中心体タンパク質BIP2はBRCA1の中心体局在と発がん機構に関与する

    齋匯成, 吉野優樹, 石岡千加史, 千葉奈津子

    第75回日本癌学会学術総会　2016/10/08

  60. 中心体制御因子としての新規BRCA1結合因子BIP2の同定

    吉野優樹, 齋匯成, 石岡千加史, 安井明, 千葉奈津子

    第75回日本癌学会学術総会　2016/10/08

  61. 新規中心体タンパク質BIP2はBRCA1の中心体局在制御に関与する

    新藤一葉, 吉野優樹, 齋匯成, 菅股眞美, 早坂美月, 千葉奈津子

    第89回日本生化学大会　2016/09/27

  62. 新規中心体タンパク質BIP2はBRCA1依存性に中心体数を制御する

    吉野優樹, 齋匯成, 菅股眞美, 安井明, 千葉奈津子

    第89回日本生化学大会　2016/09/27

  63. 新規BRCA1結合分子OLA1と協調したBARD1の中心体制御機構

    藤田拡樹, 吉野優樹, 阿部舜, 小宮山裕平, 佐々木勇人, 齋匯成, 千葉奈津子

    第33回染色体ワークショップ・第14回核ダイナミクス研究会　2016

  64. 新規BRCA1結合因子BIP2による中心体数制御の分子機構

    吉野優樹, 鈴木健太, 菅股眞美, 齋匯成, 千葉奈津子

    第33回染色体ワークショップ・第14回核ダイナミクス研究会　2016

  65. BRCA1結合分子OLA1の中心体制御機構の解析

    吉野優樹, 藤田拡樹, 飯地雄大, 齋匯成, 小宮山裕平, Linn Kullberg, 佐々木勇人, 千葉奈津子

    第33回染色体ワークショップ・第14回核ダイナミクス研究会　2016

  66. 中心体制御因子Ola1ノックアウトマウスに自然発生した造血器系腫瘍の病理組織学的解析

    飯地雄大, 吉野優樹, 中村保宏, 小河穂波, 二口充, 藤田拡樹, 渡邉利雄, 千葉奈津子

    第20回造血器腫瘍研究会　2016

  67. OLA1とBRCA1/BARD1二量体の協調的な中心体制御と発がん機構

    藤田 拡樹, 吉野 優樹, 阿部 舜, 齋 匯成, 小宮山 裕平, 石岡 千加史, 千葉 奈津子

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　2015/12

  68. Glycogen synthase kinase-3β阻害薬による中心体異常と分裂期細胞死の誘導

    吉野 優樹, 千葉 奈津子, 石岡 千加史

    日本癌学会総会記事　2015/10

  69. OLA1はBRCA1、BARD1とともに中心体数を制御する

    藤田 拡樹, 吉野 優樹, 石岡 千加史, 千葉 奈津子

    日本癌学会総会記事　2015/10

  70. Induction of mitotic catastrophe following centrosome aberration by glycogen synthase kinase-3 beta

    Yoshino Y, Chiba N, Ishioka C

    第74回日本癌学会学術総会　2015

  71. 進行再発大腸癌14例に対するレゴラフェニブの有効性と安全性に関する後方視的検討

    大石 隆之, 高橋 雅信, 吉野 優樹, 李 仁, 塩野 雅俊, 高橋 昌宏, 城田 英和, 下平 秀樹, 加藤 俊介, 石岡 千加史

    日本癌治療学会誌　2014/06

  72. 標準治療抵抗性の進行再発大腸癌14例に対するレゴラフェニブの効果と安全性に関する後ろ向き検討

    大石隆之, 高橋雅信, 吉野優樹, LEE Jin, 塩野雅俊, 高橋昌宏, 城田英和, 下平秀樹, 加藤俊介, 石岡千加史

    日本臨床腫瘍学会学術集会(CD-ROM)　2014

  73. 新規クルクミン類縁体を用いた血管新生抑制効果の検討(Anti-angiogenic potential of newly synthesized curcumin analog)

    杉山 俊輔, 吉野 優樹, 田中 正光, 栗山 正, 岩渕 好治, 石岡 千加史, 柴田 浩行

    日本癌学会総会記事　2013/10

  74. 神経線維腫症1型に併発した悪性末梢神経鞘腫瘍に対し化学療法を行った3例

    下平 秀樹, 西條 憲, 大内 康太, 高橋 秀和, 吉野 優樹, 李 仁, 佐藤 悠子, 塩野 雅俊, 加藤 俊介, 石岡 千加史

    日本内科学会雑誌　2013/02

  75. がん治療における腫瘍内科医による上腕CVポート留置術の有用性 約600症例での検討を基に

    塩野 雅俊, 高橋 信, 角道 祐一, 高橋 雅信, 坂本 康寛, 添田 大司, 吉野 優樹, 下平 秀樹, 加藤 俊介, 石岡 千加史

    日本内科学会雑誌　2013/02

  76. ゲムシタビン耐性ヒト癌細胞株におけるdeoxycytidine kinaseの不活化(Deoxycytidine kinase is frequently inactivated in acquired gemcitabine-resistant human cancer cells)

    齋木 由利子, 吉野 優樹, 福重 真一, 砂村 真琴, 石田 晶玄, 元井 冬彦, 江川 新一, 海野 倫明, 堀井 明

    日本癌学会総会記事　2012/08

  77. Clinical outcome of recombinant human soluble thrombomodulin (rTM) for patients with disseminated intravascular coagulation (DIC) complicating advanced solid cancer: Retrospective analysis

    Shin Takahashi, Kohta Ohuchi, Shunsuke Kato, Hideki Shimodaira, Yuichi Kakudo, Shoko Akiyama, Kozue Yoshida, Masatoshi Shiono, Yoshinari Okada, Shunsuke Sugiyama, Naoko Saito, Jin Lee, Takayuki Oishi, Hidekazu Takahashi, Yuki Yoshino, Chikashi Ishioka

    JOURNAL OF CLINICAL ONCOLOGY　2012/05

  78. 進行・再発悪性腫瘍に対する塩酸イリノテカンを含む薬物療法におけるUGT1A1遺伝子多型と有害事象発現との関連に対する後方視的検討

    李 仁, 秋山 聖子, 吉野 優樹, 大石 隆之, 齋藤 菜穂子, 高橋 秀和, 加藤 俊介, 角道 祐一, 下平 秀樹, 石岡 千加史

    日本内科学会雑誌　2012/02

  79. 3名の家族内感染がみられた伝染性単核症

    吉野優樹, 芦野有悟, 齊藤弘樹, 服部俊夫

    感染症学雑誌　2010

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Industrial Property Rights 2

  1. がんを治療するための医薬

    藤田 雄三, 千葉奈津子, 神宮啓一, 吉野優樹

    Property Type: Patent

  2. 相同組み換え修復活性の定量法

    吉野 優樹, 遠藤栞乃, 千葉奈津子, 渡辺剛

    Property Type: Patent

Research Projects 22

  1. 新たな中心体標的療法の開発のためのがん関連分子による中心体応答制御の統合的理解 Competitive

    千葉 奈津子, 方 震宙, 吉野 優樹, 城田 松之

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(B)

    Institution: 東北大学

    2025/04 - 2028/03

  2. 中心小体複製の組織特異性に基づくBRCA1関連乳がんの発がん機構の解明

    吉野 優樹, 千葉 奈津子

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2024/04/01 - 2027/03/31

  3. Development of cancer therapy targeting genome instability by centrosome dysregulation and DNA damage

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2022/04/01 - 2025/03/31

  4. 中心体異常とDNA損傷によるゲノム不安定性を標的とする新しいがん治療法の開発

    千葉 奈津子, 吉野 優樹, 渡部 剛, 城田 松之

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(B)

    Institution: 東北大学

    2022/04/01 - 2025/03/31

  5. BRCA1複合体の中心体制御機構の解析による組織特異的発がん機序の解明

    吉野 優樹

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(C)

    Category: 基盤研究(C)

    Institution: 東北大学

    2021/04 - 2024/03

    More details Close

    中心体は正確な細胞分裂に必要なオルガネラであり、その数の制御はゲノム安定性の維持に重要である。遺伝性乳癌卵巣癌症候群の原因遺伝子産物であるBRCA1はDNA損傷修復のほか、中心体複製制御にも寄与することが知られている。我々は中心体制御においてBRCA1とともに働く結合分子として、RACK1を同定し、その機能解析を行ってきた。これまでに、RACK1がBRCA1の中心体内での局在部位の制御に寄与することを明らかにしている。本研究ではBRCA1による中心体複製制御機構を解明するため、BRCA1の中心体内部における局在制御機構に着目し、解析を行った。 BRCA1に対するポリクローナル抗体を用いて免疫染色を行うと、中心小体と共局在するシグナル、その周囲に中心小体よりも若干広範囲に局在するシグナル、および中心体から細胞質に向けて突出する棘状のシグナルが認められる。一方、BRCA1に対する特定のモノクローナル抗体を用いた場合、前２者のシグナルのみが認められ、棘状のシグナルは染色されないことを見出していた。これらから棘状のシグナルはモノクローナル抗体のエピトープ部位に何らかの修飾を有するものと考え、エピトープの同定を行った。抗体作成に用いられた抗原領域の断片を用いて領域を絞り込み、さらに欠損変異体を作成してエピトープを２０アミノ酸領域まで絞り込むことに成功した。さらに、この領域内のセリン・スレオニン残基を変異させたところ、変異させるとモノクローナル抗体との結合性が完全に消失するスレオニン残基を同定した。 同スレオニン残基がリン酸化されたBRCA1の中心体局在を解析するため、同定したスレオニン残基がリン酸化されたペプチドを抗原に用いて抗体を作成した。これまでに作成した抗体がリン酸化BRCA1に特異的に反応することを確認した。

  6. Development of Targeting therapy for centrosome dysregulation in cancer

    Chiba Natsuko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2019/04/01 - 2022/03/31

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    Centrosomes are the major microtubule nucleation centers in animal cells and are critical for forming a bipolar mitotic spindle. Defects in the mechanisms regulating centrosome number are associated with carcinogenesis and cancer progression. Pathogenic variants of BRCA1 cause hereditary breast and ovarian cancer syndrome. We found that BRCA1 regulates the centrosome localization and the activities of the mitotic kinases, Aurora A and PLK1, and plays important roles in centrosome duplication and the centrosomes amplification induced by DNA damage with the BRCA1-binding proteins, BARD1, OLA1, and RACK1. We also showed that cancer-derived mutations and abnormal expression levels of these proteins cause abnormal centrosome duplication and centrosome amplification.

  7. 新規相同組み換え修復活性測定法による乳がん発症リスク診断法の開発

    吉野 優樹

    Offer Organization: 公益財団法人 神澤医学研究振興財団

    System: 第24回 研究助成金

    2021/04 - 2022/03

  8. BRCA1のリン酸化の時空間的動態の解析

    吉野 優樹

    Offer Organization: 公益財団法人 上原記念生命科学財団

    System: 2020年度 研究奨励金

    2021/04 - 2022/03

  9. 患者層別化のためのがん組織におけるDNA損傷修復活性測定法の開発

    吉野 優樹

    Offer Organization: 公益財団法人 中谷医工計測技術振興財団

    System: 2020年度 研究開発助成

    2020/04 - 2021/09

  10. 新たながん検査法としての相同組換え修復活性測定法の開発

    吉野 優樹

    Offer Organization: 公益財団法人 テルモ生命科学振興財団

    System: 2019年度 研究助成

    2020/04 - 2021/03

  11. 抗がん薬感受性を予測するためのがん組織におけるDNA損傷修復活性の測定法の開発 Competitive

    吉野 優樹

    Offer Organization: 中冨健康科学振興財団

    System: 研究助成金

    2019/04 - 2021/03

  12. 中心体型BRCA1複合体の破綻による組織特異的発がんの分子機序の解明 Competitive

    吉野 優樹

    Offer Organization: 日本学術振興会

    System: 科学研究費補助金 若手研究

    2018/04 - 2021/03

  13. DNA損傷修復活性の新規測定法を用いた遺伝性乳がんの非侵襲的診断法の開発 Competitive

    吉野 優樹

    Offer Organization: 公益信託 弘美医学研究助成基金

    System: 研究助成

    2019/10 - 2020/09

  14. DNA損傷修復活性の新規測定法を用いた遺伝性乳がんの非侵襲的診断法の開発 Competitive

    吉野 優樹

    Offer Organization: 公益財団法人 黒住医学研究振興財団

    System: 第27回研究助成金

    2019/10 - 2020/09

  15. 新規DNA修復活性測定法を利用した、がん予防薬・放射線障害治療薬としてのゲノム保護薬の開発 Competitive

    吉野 優樹

    Offer Organization: 公益財団法人 小柳財団

    System: 研究助成

    2019/04 - 2020/03

  16. PLK1制御を介した中心体型BRCA1複合体のがん抑制機構の解明 Competitive

    吉野 優樹

    Offer Organization: 公益財団法人住友電工グループ社会貢献基金

    System: 研究助成

    2018/03 - 2019/04

  17. Elucidation of regulatory mechanism to maintain genome stability by novel BRCA1-interacting molecules and development of cancer therapy

    CHIBA Natsuko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2016/04/01 - 2019/03/31

    More details Close

    BRCA1 is a tumor suppressor that is associated with hereditary breast and ovarian cancer. BRCA1 functions in DNA repair together with BARD1, a heterodimer partner of BRCA1. We identified BRCA1-interacting proteins, OLA1 and RACK1 and analyzed their function. OLA1 and RACK1 directly bound to BRCA1, and BARD1, localized the centrosomes, and functioned in the regulation of the centrosome duplication. RACK1 was involved in centrosomal localization of BRCA1. Abnormal level of the expression of OLA1 or RACK1 caused dysregulation of centrosome duplication. Cancer-derived variants of BRCA1, BARD1, OLA1, and RACK1 abolished their interaction and function in centrosome duplication. These results elucidated the novel regulatory mechanism by BRCA1 to maintain genome stability.

  18. がん化におけるBRCA1/PLK1相互作用の中心体内での時空間的挙動の乱れ Competitive

    吉野 優樹

    Offer Organization: 東北大学加齢医学研究所

    System: 若手研究者共同研究助成

    2017/04 - 2019/03

  19. BRCA1-RACK1-PLK1制御系の破綻による染色体不安定性の誘導と発がんの分子機構 Competitive

    吉野 優樹

    Offer Organization: 艮陵医学振興会

    System: 医学研究B

    2018/04 -

  20. 新たな中心体複製機構: BRCA1の細胞内トラフィッキングによる核・中心体クロストーク Competitive

    吉野 優樹

    Offer Organization: 日本財団

    System: 笹川科学助成

    2017/04 - 2018/03

  21. 中心体型BRCA1複合体: 治療標的としての新規BRCA1複合体のがん抑制機構 Competitive

    吉野 優樹

    Offer Organization: 日本学術振興会

    System: 科学研究費補助金 若手研究B

    2016/04 - 2018/03

  22. BRCA1の中心体トラフィッキング制御異常による染色体不安定性の誘導機構と発がん Competitive

    吉野 優樹

    Offer Organization: 癌研究振興財団

    System: がん研究助成事業

    2016/04 - 2017/03

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Teaching Experience 1

  1. Biological science B　Tohoku University