Details of the Researcher

PHOTO

Kenji Iemura
Section
Institute of Development, Aging and Cancer
Job title
Assistant Professor
Degree

  • 博士（理学）（東京大学）

e-Rad No.
50778058
Researcher ID
AAH-6531-2021

Research History 6

  • 2024/02 - Present
    Tohoku University

  • 2016/02 - Present
    Tohoku University　Institute of Development, Aging and Cancer Division of Cancer Control

  • 2012/08 - 2016/01
    Institute of Development, Aging and Cancer, Tohoku University

  • 2012/05 - 2012/07
    Institute of Development, Aging and Cancer, Tohoku University

  • 2012/04 - 2012/05
    The Institute of Medical Science, The University of Tokyo

  • 2009/04 - 2012/03
    Japan Society for the Promotion of Science　Research Fellowship for Young Scientists　DC1

Show all Show first 5

Education 2

  • The University of Tokyo　Graduate schools of Science

    2009/04 - 2012/03

  • Nagahama Institute of Bio-Science and Technology　Graduate schools of Bioscience

    2007/04 - 2009/03

Committee Memberships 1

  • 東北大学附置研究所若手アンサンブルグラント　若手アンサンブルグラントワーキング・グループ委員

    2023/04 - Present

Professional Memberships 4

  • 日本生化学会

  • 日本細胞生物学会

  • 日本癌学会

  • 日本分子生物学会

Research Interests 7

  • Chromosomal instability

  • Cell devision

  • Cancer

  • Cell cycle

  • Mitosis

  • Chromosome

  • Chromosome segregation

Research Areas 4

  • Life sciences / Tumor biology /

  • Life sciences / Genetics /

  • Life sciences / Cell biology /

  • Life sciences / Molecular biology /

Awards 5

  1. 日本細胞生物学会若手優秀発表賞

    2021　日本細胞生物学会

  2. 第1回日本癌学会若手の会最優秀賞

    2020　日本癌学会

  3. 第6回加齢医学研究所リトリート最優秀賞

    2019　東北大学加齢医学研究所

  4. 加齢医学研究所研究奨励賞

    2015　東北大学加齢医学研究所

  5. 日本細胞生物学会若手優秀発表賞

    2015　日本細胞生物学会

Papers 22

  1. CHAMP1 premature termination codon mutations found in individuals with intellectual disability cause a homologous recombination defect through haploinsufficiency. International-journal Peer-reviewed

    Yujiro Yoshizaki, Yunosuke Ouchi, Dicky Kurniawan, Eisuke Yumoto, Yuki Yoneyama, Faiza Ramadhani Rizqullah, Hiyori Sato, Mirjam Hanako Sarholz, Toyoaki Natsume, Masato T Kanemaki, Masanori Ikeda, Ayako Ui, Kenji Iemura, Kozo Tanaka

    Scientific reports　14　(1)　31904-31904　2024/12/30

    DOI： 10.1038/s41598-024-83435-y 　

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    CHAMP1 (chromosome alignment-maintaining phosphoprotein 1) plays a role in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). The CHAMP1 gene is one of the genes mutated in individuals with intellectual disability. The majority of the mutations are premature termination codon (PTC) mutations, while missense mutations have also been reported. How these mutations affect the functions of CHAMP1 has not been clarified yet. Here we investigated the effects of the CHAMP1 mutations on HR. In Epstein-Barr virus-induced lymphoblastoid cells and fibroblasts derived from individuals with CHAMP1 PTC mutations, truncated CHAMP1 proteins of the expected sizes were detected. When DSBs were induced in fibroblasts with PTC mutations, a defect in HR was detected. U2OS cells expressing the CHAMP1 mutants did not show an HR defect in the presence of endogenous wild-type (WT) CHAMP1, whereas they were unable to restore HR activity when CHAMP1 WT was depleted, suggesting that the PTC mutations are loss-of-function mutations. On the other hand, the CHAMP1 mutants with missense mutations restored HR activity when CHAMP1 WT was depleted. In DLD-1 cells, heterozygous depletion of CHAMP1 resulted in an HR defect, indicating haploinsufficiency. These results suggest that CHAMP1 PTC mutations cause an HR defect through a haploinsufficient mechanism, while CHAMP1 missense mutations do not affect the HR function of CHAMP1.

  2. Assessment of Chromosome Oscillations in Mammalian Cells by Live Cell Imaging Peer-reviewed

    Kenji Iemura, Kozo Tanaka

    Methods in Molecular Biology　157-164　2024/12/01

    Publisher: Springer US

    DOI： 10.1007/978-1-0716-4224-5_11 　

    ISSN： 1064-3745

    eISSN： 1940-6029

  3. Fibrous corona is reduced in cancer cell lines that attenuate microtubule nucleation from kinetochores Peer-reviewed

    Yudai Ishikawa, Hirotaka Fukue, Runa Iwakami, Masanori Ikeda, Kenji Iemura, Kozo Tanaka

    Cancer Science　116　(2)　420-431　2024/11/27

    Publisher: Wiley

    DOI： 10.1111/cas.16406 　

    ISSN： 1347-9032

    eISSN： 1349-7006

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    Abstract Most cancer cells show increased chromosome missegregation, known as chromosomal instability (CIN), which promotes cancer progression and drug resistance. The underlying causes of CIN in cancer cells are not fully understood. Here we found that breast cancer cell lines show a reduced kinetochore localization of ROD, ZW10, and Zwilch, components of the fibrous corona, compared with non‐transformed breast epithelial cell lines. The fibrous corona is a structure formed on kinetochores before their end‐on attachment to microtubules and plays a role in efficient kinetochore capture and the spindle assembly checkpoint. The reduction in the fibrous corona was not due to reduced expression levels of the fibrous corona components or to a reduction in outer kinetochore components. Kinetochore localization of Bub1 and CENP‐E, which play a role in the recruitment of the fibrous corona to kinetochores, was reduced in cancer cell lines, presumably due to reduced activity of Mps1, which is required for their recruitment to kinetochores through phosphorylating KNL1. Increasing kinetochore localization of Bub1 and CENP‐E in cancer cells restored the level of the fibrous corona. Cancer cell lines showed a reduced capacity to nucleate microtubules from kinetochores, which was recently shown to be dependent on the fibrous corona, and increasing kinetochore localization of Bub1 and CENP‐E restored the microtubule nucleation capacity on kinetochores. Our study revealed a distinct feature of cancer cell lines that may be related to CIN.

  4. Deficiency of CHAMP1, a gene related to intellectual disability, causes impaired neuronal development and a mild behavioural phenotype Peer-reviewed

    Masayoshi Nagai, Kenji Iemura, Takako Kikkawa, Sharmin Naher, Satoko Hattori, Hideo Hagihara, Koh-ichi Nagata, Hayato Anzawa, Risa Kugisaki, Hideki Wanibuchi, Takaya Abe, Kenichi Inoue, Kengo Kinoshita, Tsuyoshi Miyakawa, Noriko Osumi, Kozo Tanaka

    Brain Communications　4　(5)　2022/08/30

    Publisher: Oxford University Press (OUP)

    DOI： 10.1093/braincomms/fcac220 　

    eISSN： 2632-1297

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    Abstract CHAMP1 is a gene associated with intellectual disability, which was originally identified as being involved in the maintenance of kinetochore–microtubule attachment. To explore the neuronal defects caused by CHAMP1 deficiency, we established mice that lack CHAMP1. Mice that are homozygous knockout for CHAMP1 were slightly smaller than wild-type mice and died soon after birth on pure C57BL/6J background. Although gross anatomical defects were not found in CHAMP1−/− mouse brains, mitotic cells were increased in the cerebral cortex. Neuronal differentiation was delayed in CHAMP1−/− neural stem cells in vitro, which was also suggested in vivo by CHAMP1 knockdown. In a behavioural test battery, adult CHAMP1 heterozygous knockout mice showed mild memory defects, altered social interaction, and depression-like behaviours. In transcriptomic analysis, genes related to neurotransmitter transport and neurodevelopmental disorder were downregulated in embryonic CHAMP1−/− brains. These results suggest that CHAMP1 plays a role in neuronal development, and CHAMP1-deficient mice resemble some aspects of individuals with CHAMP1 mutations.

  5. High levels of chromosomal instability facilitate the tumor growth and sphere formation Peer-reviewed

    Kenji Iemura, Hayato Anzawa, Ryo Funayama, Runa Iwakami, Keiko Nakayama, Kengo Kinoshita, Kozo Tanaka

    Cancer Science　113　(8)　2727-2737　2022/06/30

    Publisher: Wiley

    DOI： 10.1111/cas.15457 　

    ISSN： 1347-9032

    eISSN： 1349-7006

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    Abstract Most cancer cells show chromosomal instability (CIN), a condition in which chromosome missegregation occurs at high rates. Growing evidence suggests that CIN is not just a consequence of, but a driving force for, oncogenic transformation, although the relationship between CIN and tumorigenesis has not been fully elucidated. Here we found that conventional two‐dimensional (2D) culture of HeLa cells, a cervical cancer‐derived cell line, was a heterogenous population containing cells with different CIN levels. Although cells with high‐CIN levels (high‐CIN cells) grew more slowly compared with cells with low‐CIN levels (low‐CIN cells) in 2D monolayer culture, they formed tumors in nude mice and larger spheres in three‐dimensional (3D) culture, which was more representative of the in vivo environment. The duration of mitosis was longer in high‐CIN cells, reflecting their higher mitotic defects. Single‐cell genome sequencing revealed that high‐CIN cells exhibited a higher karyotype heterogeneity compared with low‐CIN cells. Intriguingly, the karyotype heterogeneity was reduced in the spheres formed by high‐CIN cells, suggesting that cells with growth advantages were selected, although genomic copy number changes specific for spheres were not identified. When we examined gene expression profiles, genes related to the K‐ras signaling were upregulated, while those related to the unfolded protein response were downregulated in high‐CIN cells in 3D culture compared with 2D culture, suggesting the relevance of these genes for their survival. Our data suggested that, although CIN is disadvantageous in monolayer culture, it promotes the selection of cells with growth advantages under in vivo environments, which may lead to tumorigenesis.

  6. Attenuated Chromosome Oscillation as a Cause of Chromosomal Instability in Cancer Cells Peer-reviewed

    Kenji Iemura, Yujiro Yoshizaki, Kinue Kuniyasu, Kozo Tanaka

    Cancers　13　(18)　4531-4531　2021/09/09

    Publisher: MDPI AG

    DOI： 10.3390/cancers13184531 　

    eISSN： 2072-6694

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    Chromosomal instability (CIN) is commonly seen in cancer cells, and related to tumor progression and poor prognosis. Among the causes of CIN, insufficient correction of erroneous kinetochore (KT)-microtubule (MT) attachments plays pivotal roles in various situations. In this review, we focused on the previously unappreciated role of chromosome oscillation in the correction of erroneous KT-MT attachments, and its relevance to the etiology of CIN. First, we provided an overview of the error correction mechanisms for KT-MT attachments, especially the role of Aurora kinases in error correction by phosphorylating Hec1, which connects MT to KT. Next, we explained chromosome oscillation and its underlying mechanisms. Then we introduced how chromosome oscillation is involved in the error correction of KT-MT attachments, based on recent findings. Chromosome oscillation has been shown to promote Hec1 phosphorylation by Aurora A which localizes to the spindle. Finally, we discussed the link between attenuated chromosome oscillation and CIN in cancer cells. This link underscores the role of chromosome dynamics in mitotic fidelity, and the mutual relationship between defective chromosome dynamics and CIN in cancer cells that can be a target for cancer therapy.

  7. Chromosome oscillation promotes Aurora A–dependent Hec1 phosphorylation and mitotic fidelity Peer-reviewed

    Kenji Iemura, Toyoaki Natsume, Kayoko Maehara, Masato T. Kanemaki, Kozo Tanaka

    Journal of Cell Biology　220　(7)　2021/05/14

    Publisher: Rockefeller University Press

    DOI： 10.1083/jcb.202006116 　

    ISSN： 0021-9525

    eISSN： 1540-8140

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    Most cancer cells show chromosomal instability, a condition where chromosome missegregation occurs frequently. We found that chromosome oscillation, an iterative chromosome motion during metaphase, is attenuated in cancer cell lines. We also found that metaphase phosphorylation of Hec1 at serine 55, which is mainly dependent on Aurora A on the spindle, is reduced in cancer cell lines. The Aurora A–dependent Hec1-S55 phosphorylation level was regulated by the chromosome oscillation amplitude and vice versa: Hec1-S55 and -S69 phosphorylation by Aurora A is required for efficient chromosome oscillation. Furthermore, enhancement of chromosome oscillation reduced the number of erroneous kinetochore–microtubule attachments and chromosome missegregation, whereas inhibition of Aurora A during metaphase increased such errors. We propose that Aurora A–mediated metaphase Hec1-S55 phosphorylation through chromosome oscillation, together with Hec1-S69 phosphorylation, ensures mitotic fidelity by eliminating erroneous kinetochore–microtubule attachments. Attenuated chromosome oscillation and the resulting reduced Hec1-S55 phosphorylation may be a cause of CIN in cancer cell lines.

  8. Chromokinesin Kid and kinetochore kinesin CENP-E differentially support chromosome congression without end-on attachment to microtubules Peer-reviewed

    Kenji Iemura, Kozo Tanaka

    Nature Communications　6　(1)　2015/03/06

    DOI： 10.1038/ncomms7447 　

    ISSN： 2041-1723

    eISSN： 2041-1723

  9. Assessment of the centrosome amplification by quantification of γ-tubulin in Western blotting Peer-reviewed

    Kenji Iemura, Kazuo Kamemura, Masanao Miwa

    Analytical Biochemistry　371　(2)　256-258　2007/12

    DOI： 10.1016/j.ab.2007.08.040 　

    ISSN： 0003-2697

  10. Kinesin-like motor protein KIF23 maintains neural stem and progenitor cell pools in the developing cortex Peer-reviewed

    Sharmin Naher, Kenji Iemura, Satoshi Miyashita, Mikio Hoshino, Kozo Tanaka, Shinsuke Niwa, Jin-Wu Tsai, Takako Kikkawa, Noriko Osumi

    The EMBO Journal　44　(2)　331-355　2024/12/04

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s44318-024-00327-7 　

    eISSN： 1460-2075

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    Abstract Accurate mitotic division of neural stem and progenitor cells (NSPCs) is crucial for the coordinated generation of progenitors and mature neurons, which determines cortical size and structure. While mutations in the kinesin-like motor protein KIF23 gene have been recently linked to microcephaly in humans, the underlying mechanisms remain elusive. Here, we explore the pivotal role of KIF23 in embryonic cortical development. We characterize the dynamic expression of KIF23 in the cortical NSPCs of mice, ferrets, and humans during embryonic neurogenesis. Knockdown of Kif23 in mice results in precocious neurogenesis and neuronal apoptosis, attributed to an accelerated cell cycle exit, likely resulting from disrupted mitotic spindle orientation and impaired cytokinesis. Additionally, KIF23 depletion perturbs the apical surface structure of NSPCs by affecting the localization of apical junction proteins. We further demonstrate that the phenotypes induced by Kif23 knockdown are rescued by introducing wild-type human KIF23, but not by a microcephaly-associated variant. Our findings unveil a previously unexplored role of KIF23 in neural stem and progenitor cell maintenance via regulating spindle orientation and apical structure in addition to cytokinesis, shedding light on microcephaly pathogenesis.

  11. Oxidative stress induces chromosomal instability through replication stress in fibroblasts from aged mice Peer-reviewed

    Guan Chen, Zhenhua Li, Kenji Iemura, Kozo Tanaka

    Journal of Cell Science　136　(11)　2023/06/01

    Publisher: The Company of Biologists

    DOI： 10.1242/jcs.260688 　

    ISSN： 0021-9533

    eISSN： 1477-9137

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    ABSTRACT Chromosomal aneuploidy has been associated with aging. However, whether and how chromosomal instability (CIN), a condition frequently seen in cancer cells in which chromosome missegregation occurs at a high rate, is associated with aging is not fully understood. Here, we found that primary fibroblasts isolated from aged mice (24 months old) exhibit an increased level of chromosome missegregation and micronucleation compared with that from young mice (2 months old), concomitant with an increased rate of aneuploid cells, suggesting the emergence of CIN. Reactive oxygen species were increased in fibroblasts from aged mice, which was accompanied with mitochondrial functional decline, indicating that they are under oxidative stress. Intriguingly, antioxidant treatments reduced chromosome missegregation and micronucleation rates in cells from aged mice, suggesting a link between oxidative stress and CIN. As a cause of CIN, we found that cells from aged mice are under replication stress, which was ameliorated by antioxidant treatments. Microtubule stabilization is a potential cause of CIN promoted by replication stress. Our data demonstrate the emergence of CIN with age, and suggest an unprecedented link between oxidative stress and CIN in aging.

  12. Autocleavage of separase suppresses its premature activation by promoting binding to cyclin B1. International-journal Peer-reviewed

    Norihisa Shindo, Kazuki Kumada, Kenji Iemura, Jun Yasuda, Haruna Fujimori, Mai Mochizuki, Keiichi Tamai, Kozo Tanaka, Toru Hirota

    Cell reports　41　(9)　111723-111723　2022/11/29

    DOI： 10.1016/j.celrep.2022.111723 　

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    Accurate chromosome segregation requires timely activation of separase, a protease that cleaves cohesin during the metaphase-to-anaphase transition. However, the mechanism that maintains the inactivity of separase prior to this event remains unclear. We provide evidence that separase autocleavage plays an essential role in this process. We show that the inhibition of separase autocleavage results in premature activity before the onset of anaphase, accompanied by the formation of chromosomal bridges and spindle rocking. This deregulation is attributed to the reduced binding of cyclin B1 to separase that occurs during the metaphase-to-anaphase transition. Furthermore, when separase is mutated to render the regulation by cyclin B1 irrelevant, which keeps separase in securin-binding form, the deregulation induced by autocleavage inhibition is rescued. Our results reveal a physiological role of separase autocleavage in regulating separase, which ensures faithful chromosome segregation.

  13. TORC1 inactivation promotes APC/C-dependent mitotic slippage in yeast and human cells International-journal Peer-reviewed

    Chihiro Yamada, Aya Morooka, Seira Miyazaki, Masayoshi Nagai, Satoru Mase, Kenji Iemura, Most Naoshia Tasnin, Tsuneyuki Takuma, Shotaro Nakamura, Shamsul Morshed, Naoki Koike, Md. Golam Mostofa, Muhammad Arifur Rahman, Tasnuva Sharmin, Haruko Katsuta, Kotaro Ohara, Kozo Tanaka, Takashi Ushimaru

    iScience　25　(2)　103675-103675　2021/12

    Publisher: Elsevier BV

    DOI： 10.1016/j.isci.2021.103675 　

    ISSN： 2589-0042

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    Unsatisfied kinetochore-microtubule attachment activates the spindle assembly checkpoint to inhibit the metaphase-anaphase transition. However, some cells eventually override mitotic arrest by mitotic slippage. Here, we show that inactivation of TORC1 kinase elicits mitotic slippage in budding yeast and human cells. Yeast mitotic slippage was accompanied with aberrant aspects, such as degradation of the nucleolar protein Net1, release of phosphatase Cdc14, and anaphase-promoting complex/cyclosome (APC/C)-Cdh1-dependent degradation of securin and cyclin B in metaphase. This mitotic slippage caused chromosome instability. In human cells, mammalian TORC1 (mTORC1) inactivation also invoked mitotic slippage, indicating that TORC1 inactivation-induced mitotic slippage is conserved from yeast to mammalian cells. However, the invoked mitotic slippage in human cells was not dependent on APC/C-Cdh1. This study revealed an unexpected involvement of TORC1 in mitosis and provides information on undesirable side effects of the use of TORC1 inhibitors as immunosuppressants and anti-tumor drugs.

  14. A mathematical model of kinetochore-microtubule attachment regulated by Aurora A activity gradient describes chromosome oscillation and correction of erroneous attachments Peer-reviewed

    Manuel Alejandro, Campos Medina, Kenji Iemura, Akatsuki Kimura, Kozo Tanaka

    Biomedical Research　42　(5)　203-219　2021/09/21

    Publisher: Biomedical Research Press

    DOI： 10.2220/biomedres.42.203 　

    ISSN： 0388-6107

    eISSN： 1880-313X

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    Chromosome oscillation during metaphase is attenuated in cancer cell lines, concomitant with the reduction of Aurora A activity on kinetochores, which results in reduced mitotic fidelity. To verify the correlation between Aurora A activity, chromosome oscillation, and error correction efficiency, we developed a mathematical model of kinetochore-microtubule dynamics, based on stochastic attachment/detachment events regulated by Aurora A activity gradient centered at spindle poles. The model accurately reproduced the oscillatory movements of chromosomes, which were suppressed not only when Aurora A activity was inhibited, but also when it was upregulated, mimicking the situation in cancer cells. Our simulation also predicted efficient correction of erroneous attachments through chromosome oscillation, which was hampered by both inhibition and upregulation of Aurora A activity. Our model provides a framework to understand the physiological role of chromosome oscillation in the correction of erroneous attachments that is intrinsically related to Aurora A activity.

  15. Chromosome alignment‐maintaining phosphoprotein CHAMP1 plays a role in cell survival through regulating Mcl‐1 expression Peer-reviewed

    Maho Hino, Kenji Iemura, Masanori Ikeda, Go Itoh, Kozo Tanaka

    Cancer Science　112　(9)　3711-3721　2021/07/16

    Publisher: Wiley

    DOI： 10.1111/cas.15018 　

    ISSN： 1347-9032

    eISSN： 1349-7006

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    Abstract Antimitotic drugs such as vinca alkaloids and taxanes cause mitotic cell death after prolonged mitotic arrest. However, a fraction of cells escape from mitotic arrest by undergoing mitotic slippage, which is related to resistance to antimitotic drugs. Tipping the balance to mitotic cell death thus can be a way to overcome the drug resistance. Here we found that depletion of a mitotic regulator, CHAMP1 (chromosome alignment‐maintaining phosphoprotein, CAMP), accelerates the timing of mitotic cell death after mitotic arrest. Live cell imaging revealed that CHAMP1‐depleted cells died earlier than mock‐treated cells in the presence of antimitotic drugs that resulted in the reduction of cells undergoing mitotic slippage. Depletion CHAMP1 reduces the expression of antiapoptotic Bcl‐2 family proteins, especially Mcl‐1. We found that CHAMP1 maintains Mcl‐1 expression both at protein and mRNA levels independently of the cell cycle. At the protein level, CHAMP1 maintains Mcl‐1 stability by suppressing proteasome‐dependent degradation. Depletion of CHAMP1 reduces cell viability, and exhibits synergistic effects with antimitotic drugs. Our data suggest that CHAMP1 plays a role in the maintenance of Mcl‐1 expression, implying that CHAMP1 can be a target to overcome the resistance to antimitotic drugs.

  16. Delayed Chromosome Alignment to the Spindle Equator Increases the Rate of Chromosome Missegregation in Cancer Cell Lines Peer-reviewed

    Kinue Kuniyasu, Kenji Iemura, Kozo Tanaka

    Biomolecules　9　(1)　2018/12/28

    DOI： 10.3390/BIOM9010010 　

  17. Lateral attachment of kinetochores to microtubules is enriched in prometaphase rosette and facilitates chromosome alignment and bi-orientation establishment Peer-reviewed

    Go Itoh, Masanori Ikeda, Kenji Iemura, Mohammed Abdhullahel Amin, Sei Kuriyama, Masamitsu Tanaka, Natsuki Mizuno, Hiroko Osakada, Tokuko Haraguchi, Kozo Tanaka

    Scientific Reports　8　(1)　2018/12/01

    Publisher: Nature Publishing Group

    DOI： 10.1038/s41598-018-22164-5 　

    ISSN： 2045-2322

  18. Author Correction: Lateral attachment of kinetochores to microtubules is enriched in prometaphase rosette and facilitates chromosome alignment and bi-orientation establishment. International-journal Peer-reviewed

    Itoh G, Ikeda M, Iemura K, Amin MA, Kuriyama S, Tanaka M, Mizuno N, Osakada H, Haraguchi T, Tanaka K

    Scientific reports　8　(1)　7003-7003　2018/04

    DOI： 10.1038/s41598-018-25175-4 　

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    A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

  19. Phosphorylation of BACH1 switches its function from transcription factor to mitotic chromosome regulator and promotes its interaction with HMMR Peer-reviewed

    Jie Li, Hiroki Shima, Hironari Nishizawa, Masatoshi Ikeda, Andrey Brydun, Mitsuyo Matsumoto, Hiroki Kato, Yuriko Saiki, Liang Liu, Miki Watanabe-Matsui, Kenji Iemura, Kozo Tanaka, Takuma Shiraki, Kazuhiko Igarashi

    Biochemical Journal　475　(5)　981-1002　2018/03/15

    Publisher: Portland Press Ltd

    DOI： 10.1042/BCJ20170520 　

    ISSN： 1470-8728 0264-6021

    eISSN： 1470-8728

  20. De Novo Truncating Mutations in the Kinetochore-Microtubules Attachment GeneCHAMP1Cause Syndromic Intellectual Disability Peer-reviewed

    Bertrand Isidor, Sébastien Küry, Jill A. Rosenfeld, Thomas Besnard, Sébastien Schmitt, Shelagh Joss, Sally J Davies, Robert Roger Lebel, Alex Henderson, Christian P. Schaaf, Haley E. Streff, Yaping Yang, Vani Jain, Nodoka Chida, Xenia Latypova, Cédric Le Caignec, Benjamin Cogné, Sandra Mercier, Marie Vincent, Estelle Colin, Dominique Bonneau, Anne-Sophie Denommé, Philippe Parent, Brigitte Gilbert-Dussardier, Sylvie Odent, Annick Toutain, Amélie Piton, Christian Dina, Audrey Donnart, Pierre Lindenbaum, Eric Charpentier, Richard Redon, Kenji Iemura, Masanori Ikeda, Kozo Tanaka, Stéphane Bézieau

    Human Mutation　37　(4)　354-358　2016/02/04

    DOI： 10.1002/humu.22952 　

    ISSN： 1059-7794

    eISSN： 1098-1004

  21. CLIP-170 is required to recruit PLK1 to kinetochores during early mitosis for chromosome alignment Peer-reviewed

    Mohammed Abdullahel Amin, Go Itoh, Kenji Iemura, Masanori Ikeda, Kozo Tanaka

    Journal of Cell Science　2014/01/01

    DOI： 10.1242/jcs.150755 　

    ISSN： 0021-9533

    eISSN： 1477-9137

  22. Nucleoporin Nup188 is required for chromosome alignment in mitosis Peer-reviewed

    Go Itoh, Shiro Sugino, Masanori Ikeda, Mayumi Mizuguchi, Shin‐ichiro Kanno, Mohammed A. Amin, Kenji Iemura, Akira Yasui, Toru Hirota, Kozo Tanaka

    Cancer Science　104　(7)　871-879　2013/05/02

    DOI： 10.1111/cas.12159 　

    ISSN： 1347-9032

    eISSN： 1349-7006

Show all ︎Show first 5

Misc. 49

  1. がん細胞液性因子を介した染色体不安定性誘導機構(Mechanisms of CIN induction via cancer extracellular factors)

    家村 顕自, 田中 耕三

    日本癌学会総会記事　82回　1136-1136　2023/09

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  2. 染色体不安定性に対するがん細胞の生存戦略(Survival strategies of cancer cells against chromosomal instability)

    家村 顕自, 田中 耕三

    日本癌学会総会記事　81回　J-1033　2022/09

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  3. 染色体分配における染色体オシレーションの役割 Peer-reviewed

    家村 顕自, 田中 耕三

    生化学　94　(3)　433-437　2022/06

    Publisher: (公社)日本生化学会

    ISSN： 0037-1017

    eISSN： 2189-0544

  4. Cancer secretome induces chromosomal instability

    家村顕自, 田中耕三

    日本分子生物学会年会プログラム・要旨集(Web)　45th　2022

  5. Mitotic chromosome oscillation maintains chromosomal stability

    家村顕自, 田中耕三

    日本細胞生物学会大会(Web)　73rd　2021

  6. 分裂期染色体動態異常を介した染色体不安定性の発生機構

    家村顕自, 田中耕三

    日本癌学会学術総会抄録集(Web)　80th　2021

  7. Chromosome oscillation-mediated robust equal segregation system is suppressed together with progression of cellular senescence

    家村顕自, 田中耕三

    日本分子生物学会年会プログラム・要旨集(Web)　44th　2021

  8. がん細胞の増殖優位性獲得過程における染色体不安定性の役割

    家村顕自, 田中耕三

    日本生化学会大会(Web)　94th　2021

  9. 増殖選択圧を受けたがん細胞の増殖優位性獲得過程における染色体不安定性の役割

    家村 顕自, 田中 耕三

    日本細胞生物学会大会講演要旨集　72回　1-2　2020/06

    Publisher: (一社)日本細胞生物学会

  10. 分裂期中期における染色体動態は染色体均等分配の堅牢性に寄与する

    家村顕自, 田中耕三

    日本分子生物学会年会プログラム・要旨集(Web)　43rd　2020

  11. 分裂期中期動原体のリン酸化における空間的制御は染色体均等分配の堅牢性に寄与する

    家村顕自, 田中耕三

    日本生化学会大会(Web)　93rd　[1Z06-443)]　2020

    Publisher: (公社)日本生化学会

  12. 染色体整列因子CAMP(CHAMP1)欠損による知的障害発症メカニズムの解明

    永井正義, 永井正義, 家村顕自, 服部聡子, 吉川貴子, 萩原英雄, 安澤隼人, 木下賢吾, 大隅典子, 宮川剛, 田中耕三

    日本分子生物学会年会プログラム・要旨集(Web)　42nd　2019

  13. 加齢に伴う初代線維芽細胞の染色体安定性変化の実態とその分子基盤の解明

    陳冠, 家村顕自, 田中耕三

    日本分子生物学会年会プログラム・要旨集(Web)　42nd　2019

  14. 新規分子CAMPによる分裂期細胞死制御機構の解明

    樋野真帆, 家村顕自, 田中耕三

    日本分子生物学会年会プログラム・要旨集(Web)　42nd　2019

  15. がん細胞の増殖における染色体不安定性の役割(The role of chromosomal instability in cancer cell proliferation)

    家村 顕自, 田中 耕三

    日本癌学会総会記事　77回　1555-1555　2018/09

    Publisher: 日本癌学会

    ISSN： 0546-0476

  16. 染色体整列の効率性の低下による高頻度な誤ったキネトコア-微小管結合の形成が染色体不安定性を引き起こす

    國安絹枝, 家村顕自, 田中耕三

    日本生化学会大会(Web)　91st　[3T13m-230)]　2018

    Publisher: (公社)日本生化学会

  17. 染色体整列の遅延により染色体不安定性が生じる機構

    國安絹枝, 家村顕自, 田中耕三

    日本分子生物学会年会プログラム・要旨集(Web)　41st　2018

  18. 染色体動態異常による染色体異数化機構の解明

    家村顕自

    上原記念生命科学財団研究報告集(CD-ROM)　32　1-4　2018

    Publisher: (公財)上原記念生命科学財団

    eISSN： 2433-3441

  19. 中心体キナーゼAurora Aによる染色体振幅運動は染色体均等分配の堅牢性に寄与する

    家村顕自, 田中耕三

    日本分子生物学会年会プログラム・要旨集(Web)　41st　ROMBUNNO.2P‐0320 (WEB ONLY)　2018

  20. 分裂期染色体動態による染色体安定性の維持機構

    家村顕自, 田中耕三

    日本遺伝学会大会プログラム・予稿集　90th　102　2018

  21. 染色体オシレーションと異常な結合の修正を記述する動原体-微小管結合の数学的モデル

    Campos Manuel, 家村 顕自, 田中 耕三

    生命科学系学会合同年次大会　2017年度　[4AT19-0381)]　2017/12

    Publisher: 生命科学系学会合同年次大会運営事務局

  22. 染色体の安定性を保障する染色体均等分配の新たな制御機構

    家村 顕自, 田中 耕三

    日本癌学会総会記事　76回　IS5-2　2017/09

    Publisher: 日本癌学会

    ISSN： 0546-0476

  23. 染色体不安定性の病態生理 Aurora Aは正常細胞における染色体均等分配システムの堅牢性を保証する

    家村 顕自, 田中 耕三

    日本細胞生物学会大会講演要旨集　69回　8-8　2017/05

    Publisher: (一社)日本細胞生物学会

  24. Mechanism for efficient chromosome alignment in mitosis

    Kenji Iemura, Kozo Tanaka

    Seikagaku　89　(1)　102-104　2017/02

    Publisher: Japanese Biochemical Society

    DOI： 10.14952/SEIKAGAKU.2017.890102 　

    ISSN： 0037-1017

    eISSN： 2189-0544

  25. 神経細胞の発生及び分化における染色体整列因子CAMPの機能解析

    永井正義, 永井正義, 家村顕自, 池田真教, 田中耕三

    日本細胞生物学会大会(Web)　69th　49-49　2017

    Publisher: (一社)日本細胞生物学会

  26. 染色体整列の時空間的な遅延が染色体不安定性を引き起こす

    國安絹枝, 家村顕自, 田中耕三

    日本細胞生物学会大会(Web)　69th　65-65　2017

    Publisher: (一社)日本細胞生物学会

  27. マウス胎児脳における染色体整列因子CAMPの発現部位の同定

    永井 正義, 家村 顕自, 吉川 貴子, 大隅 典子, 田中 耕三

    生命科学系学会合同年次大会　90th　[3LBA-131]　2017

    Publisher: 生命科学系学会合同年次大会運営事務局

  28. DNA損傷と修復 染色体動態の異常による染色体不安定性の発生

    田中 耕三, 國安 絹枝, 家村 顕自

    日本癌学会総会記事　75回　S1-1　2016/10

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  29. 効率的な染色体整列の染色体安定性への関与

    國安 絹枝, 家村 顕自, 田中 耕三

    日本生化学会大会プログラム・講演要旨集　89回　[2T14-248)]　2016/09

    Publisher: (公社)日本生化学会

  30. 天然変性タンパク質としての細胞周期関連分子CAMPの機能

    池田真教, 家村顕自, 古寺哲幸, 有田恭平, 西村善文, 田中耕三

    日本蛋白質科学会年会プログラム・要旨集　16th　36　2016/05/19

  31. 細胞骨格、形態、運動を制御する分子機構 中心体キナーゼAurora Aは分裂期中期おけるキネトコア-微小管結合の修正に寄与する

    家村 顕自, 田中 耕三

    日本細胞生物学会大会講演要旨集　68回　41-41　2016/05

    Publisher: (一社)日本細胞生物学会

  32. がん細胞における染色体均等分配システム異常誘導機構の解析

    家村顕自

    かなえ医薬振興財団研究業績集(Web)　45th　2016

  33. 中心体キナーゼAurora Aは分裂期染色体動態に応答して動原体分子をリン酸化する

    家村顕自, 田中耕三

    日本分子生物学会年会プログラム・要旨集(Web)　39th　2016

  34. 脳における染色体整列因子CAMPの機能解析

    永井正義, 永井正義, 家村顕自, 池田真教, 田中耕三

    日本分子生物学会年会プログラム・要旨集(Web)　39th　2016

  35. 効率的な染色体整列の異常が染色体不安定性を引き起こす

    國安絹枝, 家村顕自, 田中耕三

    日本分子生物学会年会プログラム・要旨集(Web)　39th　2016

  36. 効率的な染色体整列の染色体安定性への関与

    小林 絹枝, 家村 顕自, 田中 耕三

    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　[3P0096]-[3P0096]　2015/12

    Publisher: (公社)日本生化学会

  37. 効率的な染色体整列の異常による染色体不安定性の出現

    田中 耕三, 家村 顕自

    日本癌学会総会記事　74回　IS1-2　2015/10

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  38. 染色体整列制御分子CAMPは分裂期停止時におけるがん細胞の生存に寄与する(CAMP is required for cell survival during mitotic arrest by anti-mitotic drugs)

    家村 顕自, 伊藤 剛, 田中 耕三

    日本癌学会総会記事　73回　J-3002　2014/09

    Publisher: 日本癌学会

    ISSN： 0546-0476

  39. 効率的な染色体整列におけるKid及びCENP-Eの機能解析

    家村 顕自, 田中 耕三

    日本細胞生物学会大会講演要旨集　37th　131-131　2014

    Publisher: (一社)日本細胞生物学会

  40. 染色体分配における核膜孔複合体構成団子Nup188の機能

    伊藤剛, 杉野史郎, 池田真教, 水口万裕美, 菅野新一郎, ABDULLAHEL Amin Mohammed, 家村顕自, 安井明, 広田亨, 田中耕三

    生化学　85　(8)　722-722　2013/08/25

    Publisher: (公社)日本生化学会

    ISSN： 0037-1017

  41. 分裂期制御研究の新局面 キネトコアと微小管の双方向性結合の成立過程の解析

    伊藤 剛, 池田 真教, 家村 顕自, Amin Mohammed Abdullahel, 田中 耕三

    日本細胞生物学会大会講演要旨集　65回　127-127　2013/05

    Publisher: (一社)日本細胞生物学会

  42. 分裂期初期におけるキネトコア-微小管結合の解析

    池田真教, 伊藤剛, 家村顕自, AMIN Mohammed Abdullahel, 田中耕三

    日本分子生物学会年会プログラム・要旨集(Web)　36th　2013

  43. 染色体整列制御分子CAMPは分裂期停止時における細胞の生存に関与する

    家村顕自, 伊藤剛, 田中耕三

    日本分子生物学会年会プログラム・要旨集(Web)　36th　2013

  44. Chromokinesin Kid and kinetochore kinesin CENP-E differentially support chromosome congression during prometaphase

    K. Iemura, G. Itoh, M. Ikeda, M. A. Amin, K. Tanaka

    MOLECULAR BIOLOGY OF THE CELL　24　2013

    ISSN： 1059-1524

    eISSN： 1939-4586

  45. キネトコアが微小管の側面に結合する分子メカニズムの解明

    伊藤剛, ABDULLAHEL Amin Mohammed, 家村顕自, 池田真教, 田中耕三

    日本分子生物学会年会プログラム・要旨集(Web)　35th　2012

  46. AMPKγは動原体-微小管結合の修正に寄与する(AMPKγ is required for correct kinetochore-microtubule attachments)

    家村 顕自, 押森 直木, 山本 雅, 大杉 美穂

    日本細胞生物学会大会講演要旨集　63回　123-123　2011/05

    Publisher: (一社)日本細胞生物学会

  47. AMPKγは分裂期における染色体整列に寄与する(AMPK-gamma is required for chromosome alignment during mitosis)

    家村 顕自, 押森 直木, 山本 雅, 大杉 美穂

    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　83回・33回　4T3-4　2010/12

    Publisher: (公社)日本生化学会

  48. 細胞分裂・DNA修復 AMPKγは分裂期における染色体整列に寄与する(Cell division and DNA repair AMPKγ is required for chromosome alignment during mitosis)

    家村 顕自, 押森 直木, 山本 雅, 大杉 美穂

    日本細胞生物学会大会講演要旨集　62回　125-125　2010/05

    Publisher: (一社)日本細胞生物学会

  49. γチューブリン定量による中心体異常増幅の判定(Quantification of the centrosome amplification by the γ-tubulin blotting)

    家村 顕自, 亀村 和生, 三輪 正直

    日本癌学会総会記事　66回　176-176　2007/08

    Publisher: 日本癌学会

    ISSN： 0546-0476

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Presentations 3

  1. がん細胞における染色体不安定性の誘導機構について Invited

    家村顕自

    お茶の水がん学アカデミア　2023/03/14

  2. がん細胞増殖における染色体不安定性の役割 Invited

    家村顕自

    第54回がん研先端研究セミナー　2019/05/24

  3. 分裂期染色体動態による染色体安定性の維持機構 Invited

    家村顕自, 田中耕三

    第90回日本遺伝学会大会

Research Projects 13

  1. Mechanisms of chromosomal instability induction via extracellular factors

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

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

    Institution: Tohoku University

    2023/04/01 - 2026/03/31

  2. 老化細胞における染色体不安定性発生機構の解明

    Offer Organization: 公益財団法人 持田記念医学薬学振興財団

    System: 持田記念研究助成金

    2023/04 - 2024/03

  3. Elucidation of the mechanism of cell-to-cell transmission of chromosomal instability

    Offer Organization: Japan Science and Technology Agency

    System: Strategic Basic Research Programs ACT-X

    2021/10 - 2024/03

  4. 染色体不安定性がん細胞の増殖優位性獲得機構を抑制する薬理活性化合物の探索

    家村顕自

    Offer Organization: 公益財団法人 薬理研究会

    System: 研究助成

    2021/09 - 2022/10

  5. Elucidation of the molecular mechanism required for the acquisition of growth advantage in CIN cancer cell

    Iemura Kenji

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Early-Career Scientists

    Institution: Tohoku University

    2020/04/01 - 2022/03/31

    More details Close

    The mechanisms underlying how environmentally adapted cells are selected from a genetically diverse cancer cell population caused by chromosomal instability are unknown. In this study, we analyzed the proliferation process, chromosome copy number and gene expression of cancer cells with different frequencies of chromosomal instability. It was found that chromosomal instability helps the generation of cells, which have activation of the KRAS pathway and clearance of unfolded protein. It has been suggested that these cells may play a role in supporting the growth advantage of CIN cancer cells.

  6. 細胞の老化に伴って引き起こされる染色体不安定性誘導機構の解明

    家村顕自

    Offer Organization: 公益財団法人 山口育英奨学会

    System: 学術研究助成

    2021/04 - 2022/03

  7. がんのヘテロジェナイエティ構築における染色体不安定性の寄与の解明 Competitive

    家村顕自

    Offer Organization: 科学研究費補助金

    System: 若手研究

    2018/04 - 2020/03

  8. がん細胞における染色体均等分配システム異常誘導機構の解析

    家村顕自

    Offer Organization: かなえ医薬振興財団

    System: 研究助成金

    2017/03 - 2018/03

  9. 染色体不安定性に起因する細胞のがん化機構の解明

    家村顕自

    Offer Organization: 公益財団法人 艮陵医学振興会

    System: 研究B

    2016/10 - 2018/03

  10. 染色体動態異常による染色体異数化機構の解明

    家村顕自

    Offer Organization: 上原記念生命科学財団

    System: 研究奨励金（研究助成）

    2016/04 - 2018/03

  11. 染色体不安定性によって誘導される発がん及びがんの悪性化機構の解明

    家村顕自

    Offer Organization: 公益財団法人 武田科学振興財団

    System: 医学系研究奨励

    2016/04 - 2018/03

  12. 分裂期キナーゼAurora Aによる染色体均等分配システムの堅牢性の解析 Competitive

    家村顕自

    Offer Organization: 科学研究費補助金

    System: 研究活動スタート支援

    2016/04 - 2018/03

  13. 中心体タンパク質Kizunaによる分裂期中心体の安定化機構の解明 Competitive

    家村顕自

    Offer Organization: 科学研究費補助金

    System: 特別研究員奨励費

    Category: 特別研究員奨励費

    Institution: 東京大学

    2009/04 - 2012/03

    More details Close

    Plk1は分裂期に機能するキナーゼとして知られており、多くの癌細胞で高発現していることから、分裂期進行阻害を標的とした新たな抗がん剤のターゲットとして期待されている、しかし同定されている基質は少なく、Plk1による分裂期進行制御機構は未解明な部分が多い。 本年度は、Kizunaと同様にPlk1基質候補分子として同定し、これまでの研究によって動原体-微小管結合修正糧に関与することが示唆されたPSX15のより詳細な機能解析を進めた。PSX15発現抑制細胞において様々なキネトコア局在分子を観察した結果、分裂期チェックポイント分子であるBubR1が不整列な染色体における姉妹キネトコアの片側にのみ局在している割合が増加していた。次に、Aurora Bによるキネトコア分子のリン酸化状態と、Aurora B-キネトコア間距離を測定したところ、不整列な染色体における外側のキネトコアに位置する分子に対するリン酸化活性は低く、AuroraB-キネトコア距離も離れていた。また、興味深いことに、PSX15発現抑制と共に染色体腕部を極から離す役割を担うKidを発現抑制すると、PSX15発現抑制細胞で見られた不整列な染色体の表現型が回復した。以上の結果から、PSX15発現抑制細胞は染色体を極へ引く力もしくは極から離す力この2つの力のバランスが崩れることで、キネトコアに過剰な張力を生み出しAurora B-キネトコア距離が離れた結果、キネトコアに対するAurora Bのキナーゼ活性が低下することで動原体-微小管結合が安定化する可能性が考えられた。分子機構に不明瞭な点が多いシンテリック結合修正に関与する新たな分子を発見できた本成果は、今後、Plk1による新たな分裂期制御機構を提唱できると共に、シンテリック結合修正における分子基盤の解明や新規分子を標的とした抗がん剤への応用も期待できる。

Show all Show first 5

Teaching Experience 3

  1. 生命科学B　東北大学

  2. 生命科学B　東北大学

  3. Life Science B　Tohoku University

Social Activities 4

  1. 仙台市青葉区PTA連合会会長

    2025/04/01 - Present

  2. 仙台市立上杉山通小学校PTA会長

    2025/04/01 - Present

  3. 仙台市立上杉山通小学校PTA副会長

    2023/04/01 - 2025/03/31

  4. 上杉チャンネット代表

    2021/11/01 - 2025/03/31

Academic Activities 4

  1. サイエンスキャッスル2022東北大会

    2022/12/18 - 2022/12/18

  2. サイエンスキャッスル2020関東大会

    2020/12/20 - 2020/12/20

    Activity type: Competition, symposium, etc.

  3. サイエンスキャッスル2019東北大会

    2019/12/14 - 2019/12/14

    Activity type: Competition, symposium, etc.

  4. サイエンスキャッスル2018東北大会

    2018/12/16 - 2018/12/16

    Activity type: Competition, symposium, etc.