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Investigation for mechanisms underlying cell cycle regulation and metabolism in stem cells

Research Project

Project/Area Number 18H05215
Research Category

Grant-in-Aid for Specially Promoted Research

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyushu University

Principal Investigator

中山 敬一  九州大学, 生体防御医学研究所, 主幹教授 (80291508)

Co-Investigator(Kenkyū-buntansha) 中山 啓子  東北大学, 医学系研究科, 教授 (60294972)
昌子 浩孝  藤田医科大学, 医科学研究センター, 助教 (00466278)
服部 聡子 (高井聡子)  藤田医科大学, 総合医科学研究所, 助教 (00415564)
Project Period (FY) 2018-04-23 – 2023-03-31
Project Status Granted (Fiscal Year 2022)
Budget Amount *help
¥512,720,000 (Direct Cost: ¥394,400,000、Indirect Cost: ¥118,320,000)
Fiscal Year 2022: ¥96,200,000 (Direct Cost: ¥74,000,000、Indirect Cost: ¥22,200,000)
Fiscal Year 2021: ¥112,970,000 (Direct Cost: ¥86,900,000、Indirect Cost: ¥26,070,000)
Fiscal Year 2020: ¥121,160,000 (Direct Cost: ¥93,200,000、Indirect Cost: ¥27,960,000)
Fiscal Year 2019: ¥109,850,000 (Direct Cost: ¥84,500,000、Indirect Cost: ¥25,350,000)
Fiscal Year 2018: ¥72,540,000 (Direct Cost: ¥55,800,000、Indirect Cost: ¥16,740,000)
Keywords細胞周期 / 代謝 / 幹細胞 / プロテオミクス
Outline of Annual Research Achievements

われわれは以前、細胞周期の静止状態を維持するp57遺伝子が造血幹細胞や神経幹細胞といった代表的な組織幹細胞に特異的に発現することを発見しており、このp57の発現を指標とすることで、腸管においても新たな幹細胞集団を同定できるのではないかと考えた。われわれの予想通り、造血幹細胞や神経幹細胞の細胞周期停止に重要なp57遺伝子が、腸管上皮においても稀少な細胞集団に特異的に発現していることを発見した。そこでp57の系統追跡マウスを作製し、p57発現細胞の挙動を解析した結果、p57発現細胞は通常の状態では分化細胞の一種として存在しているが、組織がダメージを受けると脱分化して幹細胞となり、腸管の再生に重要な役割を果たすことがわかった。さらに腸管上皮を1細胞RNA-seq法によって解析したところ、再生途上のp57発現細胞では本来成体腸管には発現していないはずの胎児腸管の遺伝子群や胃上皮の遺伝子群が高発現していることがわかり、幹細胞性獲得の過程において通常の成体腸管とはまったく異なった細胞状態を経ていることが明らかとなった。つまり腸管の傷害後再生においては、分化した細胞の遺伝子発現プロファイルをダイナミックに作り変える(=リプログラミングする)ことで脱分化を引き起こし、新たな幹細胞集団を作り出していると考える。われわれは、この時間的(胎児返り)・空間的(胃上皮様変化)なリプログラミングを「時空間的リプログラミング」と名付けた。p57発現細胞はまた、Apc変異マウスで自然発生する腸管腫瘍においてもがん幹細胞として機能しており、かつ腫瘍内でも上記と同様の時空間的リプログラミング現象が起こっていることが判明した。将来的には、このような時空間的リプログラミングのメカニズムを研究することにより、がん幹細胞を根絶する治療法を確立できると期待される。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

既にアリル特異的Hi-Cシステムは開発済であるので、これを用いてp57インプリンティング領域のTADをESCとASCにおいて調べたところ、解像度の点で満足すべき結果が得られなかった。そこでさらに高解像度のTAD解析を行うため、4Cによる解析も同様に行ったところ高解像度のTAD解析に成功し、新たなエンハンサー領域の同定に成功した。またp57陽性細胞がどのような幹細胞機能を有するかについて、腸管と胃において系統追跡実験を施行し、一部は論文として発表した(Higa et al., Nat. Commun. 13: 1500, 2022)。さらに腫瘍化において、p57陽性幹細胞が果たす役割についても明らかにすることができ、現在治療法の開発についても基礎理論の形成ができつつある。このように全体の進捗は順調に進んでいる。

Strategy for Future Research Activity

1)高解像度4C解析によって同定されたエンハンサー領域を欠損した遺伝子改変マウスを作製し、p57の発現、ゲノムインプリンティング、幹細胞の細胞周期およびその機能、にどのような影響をもたらすかを検討する。
2)胃におけるp57陽性幹細胞の性質を明らかにする。特にこの幹細胞は迷走神経支配を受けている可能性があるため、迷走神経の切断実験を行い、幹細胞性の変化を検討する。
3)その他の細胞周期-代謝系に影響を与える分子群の研究、特にc-Myc-Fbxw7系やp53-CHD8系等もp57/Skp2系と同様に細胞周期と代謝制御の接点に位置することがわれわれの研究から分かっており、それらについてもノックアウトマウスの解析を進める。

Assessment Rating
Interim Assessment Comments (Rating)

A: In light of the aim of introducing the research area into the research categories, the expected progress has been made in research.

Report

(8 results)
  • 2021 Annual Research Report
  • 2020 Abstract (Interim Assessment) ( PDF )   Annual Research Report   Interim Assessment (Comments) ( PDF )
  • 2019 Annual Research Report
  • 2018 Abstract ( PDF )   Comments on the Screening Results ( PDF )   Annual Research Report

Research Products

(82 results)

All 2022 2021 2020 2019 2018 Other

All Journal Article (55 results) (of which Int'l Joint Research: 17 results,  Peer Reviewed: 55 results,  Open Access: 46 results) Presentation (20 results) (of which Int'l Joint Research: 4 results,  Invited: 19 results) Book (1 results) Remarks (2 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 1 results)

  • [Journal Article] Spatiotemporal reprogramming of differentiated cells underlies regeneration and neoplasia in the intestinal epithelium2022

    • Author(s)
      Higa Tsunaki、Okita Yasutaka、Matsumoto Akinobu、Nakayama Shogo、Oka Takeru、Sugahara Osamu、Koga Daisuke、Takeishi Shoichiro、Nakatsumi Hirokazu、Hosen Naoki、Robine Sylvie、Taketo Makoto M.、Sato Toshiro、Nakayama Keiichi I.
    • Journal Title

      Nature Communications

      Volume: 13 Pages: 1500-1500

    • DOI

      10.1038/s41467-022-29165-z

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Kastor and Polluks polypeptides encoded by a single gene locus cooperatively regulate VDAC and spermatogenesis.2022

    • Author(s)
      Mise S#, Matsumoto A#*, Shimada K, Hosaka T, Takahashi M, Ichihara K, Shimizu H, Shiraishi C, Saito D, Suyama M, Yasuda T, Ide T, Izumi Y, Bamba T, Kimura-Someya T, Shirouzu M, Miyata H, Ikawa M, Nakayama KI*.
    • Journal Title

      Nature Communications

      Volume: 13(1) Pages: 1071-1071

    • DOI

      10.1038/s41467-022-28677-y

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multi-omics-based label-free metabolic flux inference reveals obesity-associated dysregulatory mechanisms in liver glucose metabolism2022

    • Author(s)
      Uematsu Saori、Ohno Satoshi、Tanaka Kaori Y.、Hatano Atsushi、Kokaji Toshiya、Ito Yuki、Kubota Hiroyuki、Hironaka Ken-ichi、Suzuki Yutaka、Matsumoto Masaki、Nakayama Keiichi I.、Hirayama Akiyoshi、Soga Tomoyoshi、Kuroda Shinya
    • Journal Title

      iScience

      Volume: 25 Pages: 103787-103787

    • DOI

      10.1016/j.isci.2022.103787

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combinatorial analysis of translation dynamics reveals eIF2 dependence of translation initiation at near-cognate codons2021

    • Author(s)
      Ichihara Kazuya、Matsumoto Akinobu、Nishida Hiroshi、Kito Yuki、Shimizu Hideyuki、Shichino Yuichi、Iwasaki Shintaro、Imami Koshi、Ishihama Yasushi、Nakayama Keiichi I
    • Journal Title

      Nucleic Acids Research

      Volume: 49 Pages: 7298-7317

    • DOI

      10.1093/nar/gkab549

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The autism-associated protein CHD8 is required for cerebellar development and motor function2021

    • Author(s)
      Kawamura Atsuki、Katayama Yuta、Kakegawa Wataru、Ino Daisuke、Nishiyama Masaaki、Yuzaki Michisuke、Nakayama Keiichi I.
    • Journal Title

      Cell Rep

      Volume: 35 Pages: 108932-108932

    • DOI

      10.1016/j.celrep.2021.108932

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An extensive and dynamic trans-omic network illustrating prominent regulatory mechanisms in response to insulin in the liver2021

    • Author(s)
      Matsuzaki Fumiko、Uda Shinsuke、Yamauchi Yukiyo、Matsumoto Masaki、Soga Tomoyoshi、Maehara Kazumitsu、Ohkawa Yasuyuki、Nakayama Keiichi I.、Kuroda Shinya、Kubota Hiroyuki
    • Journal Title

      Cell Rep.

      Volume: 36 Pages: 109569-109569

    • DOI

      10.1016/j.celrep.2021.109569

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification and characterization of novel proteins associated with CHD42021

    • Author(s)
      Sakaguchi Chihiro、Ichihara Kazuya、Nita Akihiro、Katayama Yuta、Nakayama Keiichi I.
    • Journal Title

      Genes to Cells

      Volume: 27 Pages: 61-71

    • DOI

      10.1111/gtc.12909

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The heavy chain of 4F2 antigen promote prostate cancer progression via SKP-22021

    • Author(s)
      Maimaiti Maihulan、Sakamoto Shinichi、Sugiura Masahiro、Kanesaka Manato、Fujimoto Ayumi、Matsusaka Keisuke、Xu Minhui、Ando Keisuke、Saito Shinpei、Wakai Ken、Imamura Yusuke、Nakayama Keiichi、Kanai Yoshikatsu、Kaneda Atsushi、Ikehara Yuzuru、Ikeda Jun-Ichiro、Anzai Naohiko、Ichikawa Tomohiko
    • Journal Title

      Scientific Reports

      Volume: 11 Pages: 11478-11478

    • DOI

      10.1038/s41598-021-90748-9

    • NAID

      130008144976

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oxytocin ameliorates impaired social behavior in a Chd8 haploinsufficiency mouse model of autism2021

    • Author(s)
      Cherepanov Stanislav M.、Gerasimenko Maria、Yuhi Teruko、Furuhara Kazumi、Tsuji Chiharu、Yokoyama Shigeru、Nakayama Keiichi I.、Nishiyama Masaaki、Higashida Haruhiro
    • Journal Title

      BMC Neuroscience

      Volume: 22 Pages: 32-32

    • DOI

      10.1186/s12868-021-00631-6

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A ubiquitin-like protein encoded by the “noncoding” RNA TINCR promotes keratinocyte proliferation and wound healing2021

    • Author(s)
      Nita Akihiro、Matsumoto Akinobu、Tang Ronghao、Shiraishi Chisa、Ichihara Kazuya、Saito Daisuke、Suyama Mikita、Yasuda Tomoharu、Tsuji Gaku、Furue Masutaka、Katayama Bumpei、Ozawa Toshiyuki、Murata Teruasa、Dainichi Teruki、Kabashima Kenji、Hatano Atsushi、Matsumoto Masaki、Nakayama Keiichi I.
    • Journal Title

      PLOS Genetics

      Volume: 17 Pages: 1009686-1009686

    • DOI

      10.1371/journal.pgen.1009686

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders2021

    • Author(s)
      Johmura Y, Nakanishi M, et al
    • Journal Title

      Science

      Volume: 371 Issue: 6526 Pages: 265-270

    • DOI

      10.1126/science.abb5916

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The autism-related protein CHD8 contributes to the stemness and differentiation of mouse hematopoietic stem cells2021

    • Author(s)
      Nita Akihiro、Muto Yoshiharu、Katayama Yuta、Matsumoto Akinobu、Nishiyama Masaaki、Nakayama Keiichi I.
    • Journal Title

      Cell Reports

      Volume: 34 Pages: 108688-108688

    • DOI

      10.1016/j.celrep.2021.108688

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A universal molecular prognostic score for gastrointestinal tumors2021

    • Author(s)
      Shimizu Hideyuki、Nakayama Keiichi I.
    • Journal Title

      npj Genomic Medicine

      Volume: 6 Pages: 1-10

    • DOI

      10.1038/s41525-021-00172-1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Trans-omic analysis reveals obesity-associated dysregulation of inter-organ metabolic cycles between the liver and skeletal muscle2021

    • Author(s)
      Egami Riku、Kokaji Toshiya、Hatano Atsushi、et al.
    • Journal Title

      iScience

      Volume: 24 Pages: 102217-102217

    • DOI

      10.1016/j.isci.2021.102217

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Acetaldehyde dehydrogenase 2 deficiency increases mitochondrial reactive oxygen species emission and induces mitochondrial protease Omi/HtrA2 in skeletal muscle.2020

    • Author(s)
      Wakabayashi Y, Tamura Y, Kouzaki K, Kikuchi N, Hiranuma K, Menuki K, Tajima T, Yamanaka Y, Sakai A, Nakayama KI, Kawamoto T, Kitagawa K, Nakazato K.
    • Journal Title

      American Journal of Physiology-Regulatory, Integrative and Comparative Physiology

      Volume: 318 Pages: 667-690

    • DOI

      10.1152/ajpregu.00089.2019

    • NAID

      120007089104

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Autism-Related Protein SETD5 Controls Neural Cell Proliferation through Epigenetic Regulation of rDNA Expression2020

    • Author(s)
      Tadashi Nakagawa, Satoko Hattori, Tsuyoshi Miyakawa, Keiko Nakayama
    • Journal Title

      iScience

      Volume: 23 Issue: 4 Pages: 101030-101030

    • DOI

      10.1016/j.isci.2020.101030

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell cycle-dependent localization of the proteasome to chromatin2020

    • Author(s)
      Kito Yuki、Matsumoto Masaki、Hatano Atsushi、Takami Tomoyo、Oshikawa Kiyotaka、Matsumoto Akinobu、Nakayama Keiichi I.
    • Journal Title

      Sci Rep

      Volume: 10 Pages: 5801-5801

    • DOI

      10.1038/s41598-020-62697-2

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oligodendrocyte dysfunction due to Chd8 mutation gives rise to behavioral deficits in mice2020

    • Author(s)
      Kawamura Atsuki、Katayama Yuta、Nishiyama Masaaki、Shoji Hirotaka、Tokuoka Kota、Ueta Yoshifumi、Miyata Mariko、Isa Tadashi、Miyakawa Tsuyoshi、Hayashi-Takagi Akiko、Nakayama Keiichi I
    • Journal Title

      Hum. Mol. Genet.

      Volume: - Pages: 1274-1291

    • DOI

      10.1093/hmg/ddaa036

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Skp2 contributes to cell cycle progression in trophoblast stem cells and to placental development.2020

    • Author(s)
      Yamauchi, Y., Nita, A., Nishiyama, M., Muto, Y., Shimizu, H., Nakatsumi, H., Nakayama, K. I.
    • Journal Title

      Genes to Cells

      Volume: XX Pages: 427-438

    • DOI

      10.1111/gtc.12769

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protrudin and PDZD8 contribute to neuronal integrity by promoting lipid extraction required for endosome maturation2020

    • Author(s)
      Shirane Michiko、Wada Mariko、Morita Keiko、Hayashi Nahoki、Kunimatsu Reina、Matsumoto Yuki、Matsuzaki Fumiko、Nakatsumi Hirokazu、Ohta Keisuke、Tamura Yasushi、Nakayama Keiichi I.
    • Journal Title

      Nat. Commun.

      Volume: 11 Pages: 4576-4576

    • DOI

      10.1038/s41467-020-18413-9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A phospho-switch controls RNF43-mediated degradation of Wnt receptors to suppress tumorigenesis2020

    • Author(s)
      Tsukiyama Tadasuke、Zou Juqi、Kim Jihoon、Ogamino Shohei、Shino Yuki、Masuda Takamasa、Merenda Alessandra、Matsumoto Masaki、Fujioka Yoichiro、Hirose Tomonori、Terai Sayuri、Takahashi Hidehisa、Ishitani Tohru、Nakayama Keiichi I.、Ohba Yusuke、Koo Bon-Kyoung、Hatakeyama Shigetsugu
    • Journal Title

      Nat Commun

      Volume: 11 Pages: 1-16

    • DOI

      10.1038/s41467-020-18257-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Protrudin-deficient mice manifest depression-like behavior with abnormalities in activity, attention, and cued fear-conditioning2020

    • Author(s)
      Shirane Michiko、Shoji Hirotaka、Hashimoto Yutaka、Katagiri Hiroyuki、Kobayashi Shizuka、Manabe Toshiya、Miyakawa Tsuyoshi、Nakayama Keiichi I.
    • Journal Title

      Molecular Brain

      Volume: 13 Pages: 146-146

    • DOI

      10.1186/s13041-020-00693-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chd8 mutation in oligodendrocytes alters microstructure and functional connectivity in the mouse brain2020

    • Author(s)
      Kawamura Atsuki、Abe Yoshifumi、Seki Fumiko、Katayama Yuta、Nishiyama Masaaki、Takata Norio、Tanaka Kenji F.、Okano Hideyuki、Nakayama Keiichi I.
    • Journal Title

      Molecular Brain

      Volume: 13 Pages: 146-146

    • DOI

      10.1186/s13041-020-00699-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of Fbxw7 impairs development of and induces heterogeneous tumor formation in the mouse mammary gland2020

    • Author(s)
      Onoyama Ichiro、Nakayama Shogo、Shimizu Hideyuki、Nakayama Keiichi I.
    • Journal Title

      Cancer Research

      Volume: 80 Pages: 5515-5530

    • DOI

      10.1158/0008-5472.can-20-0271

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transomics analysis reveals allosteric and gene regulation axes for altered hepatic glucose-responsive metabolism in obesity2020

    • Author(s)
      Kokaji Toshiya、Hatano Atsushi、Ito Yuki、et al.
    • Journal Title

      Sci Signal.

      Volume: 13 Pages: 1236-1236

    • DOI

      10.1126/scisignal.aaz1236

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A shift in glutamine nitrogen metabolism contributes to malignant progression of cancer.2020

    • Author(s)
      Kodama M, Oshikawa K, Shimizu H, Yoshioka S, Takahashi M, Izumi Y, Bamba T, Tateishi C, Tomonaga T, Matsumoto M*, Nakayama KI*.
    • Journal Title

      Nat Commun

      Volume: 11 Pages: 1320-1320

    • DOI

      10.1038/s41467-020-15136-9

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The role of Mediator and Little Elongation Complex in transcription termination.2020

    • Author(s)
      Takahashi H, Ranjan A, Chen S, Suzuki H, Shibata M, Hirose T, Hirose H, Sasaki K, Abe R, Chen K, He Y, Zhang Y, Takigawa I, Tsukiyama T, Watanabe M, Fujii S, Iida M, Yamamoto J, Yamaguchi Y, Suzuki Y, Matsumoto M, Nakayama K. I, Washburn M. P, Saraf A, Florens L, Sato S, Tomomori-Sato C, Conaway R. C, Conaway J. W, Hatakeyama S.
    • Journal Title

      Nat. Commun.

      Volume: 11 Pages: 1063-1063

    • DOI

      10.1038/s41467-020-14849-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development2020

    • Author(s)
      Laukoter Susanne、Beattie Robert、Pauler Florian M.、Amberg Nicole、Nakayama Keiichi I.、Hippenmeyer Simon
    • Journal Title

      Nature Communications

      Volume: 11 Pages: 195-195

    • DOI

      10.1038/s41467-019-14077-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Artificial intelligence in oncology2020

    • Author(s)
      Shimizu Hideyuki、Nakayama Keiichi I.
    • Journal Title

      Cancer Science

      Volume: 未定

    • DOI

      10.1111/cas.14377

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recent insight into the role of FBXW7 as a tumor suppressor2020

    • Author(s)
      Yumimoto Kanae、Nakayama Keiichi I.
    • Journal Title

      Seminars in Cancer Biology

      Volume: 未定 Pages: 1-15

    • DOI

      10.1016/j.semcancer.2020.02.017

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Drug repositioning in cancer: The current situation in Japan.2020

    • Author(s)
      Masuda T, Tsuruda Y, Matsumoto Y, Uchida H, Nakayama KI, Mimori K.
    • Journal Title

      Cancer Science

      Volume: 111(4) Pages: 1039-1046

    • DOI

      10.1111/cas.14318

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phase I dose‐escalation trial to repurpose propagermanium, an oral CCL2 inhibitor, in patients with breast cancer2020

    • Author(s)
      Masuda Takaaki、Noda Miwa、Kogawa Takahiro、Kitagawa Dai、Hayashi Naoki、Jomori Takahito、Nakanishi Yoichi、Nakayama Keiichi I.、Ohno Shinji、Mimori Koshi
    • Journal Title

      Cancer Sci.

      Volume: 111 Pages: 924-931

    • DOI

      10.1111/cas.14306

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Production of BBF2H7‐derived small peptide fragments via endoplasmic reticulum stress‐dependent regulated intramembrane proteolysis2020

    • Author(s)
      Matsuhisa Koji、Saito Atsushi、Cai Longjie、Kaneko Masayuki、Okamoto Takumi、Sakaue Fumika、Asada Rie、Urano Fumihiko、Yanagida Kanta、Okochi Masayasu、Kudo Yukitsuka、Matsumoto Masaki、Nakayama Keiichi I.、Imaizumi Kazunori
    • Journal Title

      The FASEB Journal

      Volume: 34 Pages: 865-880

    • DOI

      10.1096/fj.201901748r

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Knockout Mouse Models Provide Insight into the Biological Functions of CRL1 Components.2020

    • Author(s)
      Nakagawa T, Nakayama K, Nakayama KI.
    • Journal Title

      Advances in experimental medicine and biology

      Volume: 1217 Pages: 147-171

    • DOI

      10.1007/978-981-15-1025-0_10

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Fail-Safe System to Prevent Oncogenesis by Senescence Is Targeted by SV40 Small T Antigen2020

    • Author(s)
      Kiyotaka Oshikawa, Masaki Matsumoto, Manabu Kodama, Hideyuki Shimizu, Keiichi I Nakayama
    • Journal Title

      Oncogene

      Volume: 39 Pages: 2170-2186

    • DOI

      10.1038/s41388-019-1139-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterizing vulnerable brain areas and circuits in mouse models of autism: Towards understanding pathogenesis and new therapeutic approaches.2020

    • Author(s)
      Hui K, Katayama Y, Nakayama KI, Nomura J, Sakurai T.
    • Journal Title

      Neurosci Biobehav Rev .

      Volume: 印刷中 Pages: 30121-0

    • DOI

      10.1016/j.neubiorev.2018.08.001

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The pericentromeric protein shugoshin 2 cooperates with HSF1 in heat shock response and RNA Pol II recruitment2019

    • Author(s)
      Takii Ryosuke、Fujimoto Mitsuaki、Matsumoto Masaki、Srivastava Pratibha、Katiyar Arpit、Nakayama Keiich I、Nakai Akira
    • Journal Title

      EMBO Journal

      Volume: 38

    • DOI

      10.15252/embj.2019102566

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Frequent Detection of Pituitary-Derived PrPres in Human Prion Diseases2019

    • Author(s)
      Honda Hiroyuki、Matsumoto Masaki、Shijo Masahiro、Hamasaki Hideomi、Sadashima Shoko、Suzuki Satoshi O、Aishima Shinichi、Kai Keita、Nakayama Keiichi I、Sasagasako Naokazu、Iwaki Toru
    • Journal Title

      Journal of Neuropathology & Experimental Neurology

      Volume: 78 Pages: 922-929

    • DOI

      10.1093/jnen/nlz075

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A 23 gene-based molecular prognostic score precisely predicts overall survival of breast cancer patients2019

    • Author(s)
      Shimizu H, Nakayama KI
    • Journal Title

      EBioMedicine

      Volume: 46 Pages: 150-159

    • DOI

      10.1016/j.ebiom.2019.07.046

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potentials of C-C Motif Chemokine 2-C-C Chemokine Receptor Type 2 Blockers Including Propagermanium as Anticancer Agents2019

    • Author(s)
      Yumimoto Kanae、Sugiyama Shigeaki、Mimori Koshi、Nakayama Keiichi I.
    • Journal Title

      Cancer Sci.

      Volume: 110 Pages: 2090-2099

    • DOI

      10.1111/cas.14075

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis.2019

    • Author(s)
      Muto Y., Moroishi T., Ichihara K., Nishiyama M., Shimizu H., Eguchi H., Moriya K., Koike K., Mimori K., Mori M., Katayama Y., Nakayama KI.
    • Journal Title

      J. Exp. Med.

      Volume: 216 Issue: 4 Pages: 950-965

    • DOI

      10.1084/jem.20180900

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SCF(Fbxw7) ubiquilylates KLF7 for degradation in a manner dependent on GSK-3-mediated phosphorylation.2019

    • Author(s)
      Sugiyama S., Yumimoto K., Inoue I., Nakayama KI.
    • Journal Title

      Genes Cells

      Volume: 印刷中 Pages: 354-365

    • DOI

      10.1111/gtc.12680

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prevention of cancer dormancy by Fbxw7 ablation eradicates disseminated tumor cells.2019

    • Author(s)
      Shimizu H., Takeishi S., Nakatsumi H., Nakayama KI.
    • Journal Title

      JCI Insight

      Volume: 4

    • DOI

      10.1172/jci.insight.125138

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reconstruction of global regulatory network from signaling to cellular functions using phosphoproteomic data2019

    • Author(s)
      Kawata Kentaro、Yugi Katsuyuki、Hatano Atsushi、Kokaji Toshiya、Tomizawa Yoko、Fujii Masashi、Uda Shinsuke、Kubota Hiroyuki、Matsumoto Masaki、Nakayama Keiichi I.、Kuroda Shinya
    • Journal Title

      Genes Cells

      Volume: 24 Pages: 82-93

    • DOI

      10.1111/gtc.12655

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Peroxisome biogenesis deficiency attenuates the BDNF-TrkB pathway-mediated development of the cerebellum2018

    • Author(s)
      Abe Yuichi、Honsho Masanori、Itoh Ryota、Kawaguchi Ryoko、Fujitani Masashi、Fujiwara Kazushirou、Hirokane Masaaki、Matsuzaki Takashi、Nakayama Keiko、Ohgi Ryohei、Marutani Toshihiro、Nakayama Keiichi I、Yamashita Toshihide、Fujiki Yukio
    • Journal Title

      Life Sci. Alliance.

      Volume: 1 Pages: 1-17

    • DOI

      10.26508/lsa.201800062

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bcl11b sets pro-T cell fate by site-specific cofactor recruitment and by repressing Id2 and Zbtb162018

    • Author(s)
      Hosokawa Hiroyuki、Romero-Wolf Maile、Yui Mary A.、Ungerb?ck Jonas、Quiloan Maria L. G.、Matsumoto Masaki、Nakayama Keiichi I.、Tanaka Tomoaki、Rothenberg Ellen V.
    • Journal Title

      Nature Immunology

      Volume: 19 Pages: 1427-1440

    • DOI

      10.1038/s41590-018-0238-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Brain-Derived Neurotrophic Factor Improves Limited Exercise Capacity in Mice With Heart Failure2018

    • Author(s)
      Matsumoto Junichi、et al. Hatakeyama Shigetsugu、Matsumoto Masaki、Nakayama Keiichi I.、Otsuka Yutaro、Sabe Hisataka、Tsutsui Hiroyuki、Anzai Toshihisa
    • Journal Title

      Circulation

      Volume: 138 Pages: 2064-2066

    • DOI

      10.1161/circulationaha.118.035212

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Trans-omic Analysis Reveals Selective Responses to Induced and Basal Insulin across Signaling, Transcriptional, and Metabolic Networks2018

    • Author(s)
      Kawata Kentaro、Hatano Atsushi、Yugi Katsuyuki、Kubota Hiroyuki、Sano Takanori、Fujii Masashi、Tomizawa Yoko、Kokaji Toshiya、Tanaka Kaori Y.、Uda Shinsuke、Suzuki Yutaka、Matsumoto Masaki、Nakayama Keiichi I.、Saitoh Kaori、Kato Keiko、Ueno Ayano、Ohishi Maki、Hirayama Akiyoshi、Soga Tomoyoshi、Kuroda Shinya
    • Journal Title

      iScience

      Volume: 7 Pages: 212-229

    • DOI

      10.1016/j.isci.2018.07.022

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glutamate-rich WD40 repeat containing 1 regulates ribosomal protein L23 levels via the ubiquitin-proteasome system.2018

    • Author(s)
      Watanabe, S., Fujiyama, H., Takafuji, T., Kayama, K., Matsumoto, M., Nakayama, KI., Yoshida, K., Sugimoto, N. (Corresponding author), and Fujita, M.
    • Journal Title

      Journal of Cell Science

      Volume: 131 Pages: 213009-213009

    • DOI

      10.1242/jcs.213009

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcription Factor PU.1 Represses and Activates Gene Expression in Early T Cells by Redirecting Partner Transcription Factor Binding2018

    • Author(s)
      Hosokawa Hiroyuki、Ungerb?ck Jonas、Wang Xun、Matsumoto Masaki、Nakayama Keiichi I.、Cohen Sarah M.、Tanaka Tomoaki、Rothenberg Ellen V.
    • Journal Title

      Immunity

      Volume: 48

    • DOI

      10.1016/j.immuni.2018.04.024

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Methylphenidate and Guanfacine Ameliorate ADHD-Like Phenotypes in <b><i>Fez1</i></b>-Deficient Mice2018

    • Author(s)
      Sumitomo Akiko、Saka Ayumi、Ueta Keisho、Horike Kouta、Hirai Kazuko、Gamo Nao J.、Hikida Takatoshi、Nakayama Keiichi I.、Sawa Akira、Sakurai Takeshi、Tomoda Toshifumi
    • Journal Title

      Molecular Neuropsychiatry

      Volume: 3 Pages: 223-233

    • DOI

      10.1159/000488081

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nuclear-cytoplasmic shuttling protein PP2AB56 contributes to mTORC1-dependent dephosphorylation of FOXKI.2018

    • Author(s)
      Nakatsumi H., Oka T., Higa T., Shirane M., Nakayama KI.
    • Journal Title

      Genes Cells

      Volume: 23 Pages: 599-605

    • DOI

      10.1111/gtc.12597

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TMEM55B contributes to lysosomal homeostasis and amino acid-induced mTORC1 activation2018

    • Author(s)
      Hashimoto Yutaka、Shirane Michiko、Nakayama Keiichi I.
    • Journal Title

      Genes to Cells

      Volume: 23 Pages: 418-434

    • DOI

      10.1111/gtc.12583

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hidden Peptides Encoded by Putative Noncoding RNAs2018

    • Author(s)
      Matsumoto A., Nakayama KI.
    • Journal Title

      Cell Struct. Funct.

      Volume: 18;43(1) Issue: 1 Pages: 75-83

    • DOI

      10.1247/csf.18005

    • NAID

      130006742309

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The promise of targeted proteomics for quantitative network biology2018

    • Author(s)
      Matsumoto Masaki、Nakayama Keiichi I
    • Journal Title

      Curr Opin Biotechnol.

      Volume: 54 Pages: 88-97

    • DOI

      10.1016/j.copbio.2018.02.014

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] Life sciences in the near future: Towards an era of data-driven sciences with artificial intelligence2022

    • Author(s)
      Nakayama KI, Matsumoto M
    • Organizer
      The 30th Hot Spring Harbor International Symposium: New technologies meet Biology
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 第二のワールブルグ効果:がんにおけるグルタミン由来窒素代謝の変化2021

    • Author(s)
      中山敬一
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] これからの生命科学研究:オミクスから人工知能まで2021

    • Author(s)
      中山敬一
    • Organizer
      東日本研究医養成プログラム 第11回 「夏のリトリート」
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] がん幹細胞の撲滅による新しいがん治療法2021

    • Author(s)
      中山敬一
    • Organizer
      第一回日本放射線影響学会・若手部会 放射線影響研究会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 次世代プロテオミクスが拓く医学生物学の新地平:90年来のがんの謎を解く2020

    • Author(s)
      中山敬一
    • Organizer
      第9回生命医薬情報学連合大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] がん幹細胞における細胞周期制御:がん撲滅のための治療標的としての期待2020

    • Author(s)
      中山敬一
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] グルタミンからの窒素代謝の変化はがんの悪性進化に必須である:”第二のワールブルグ効果”の発見2020

    • Author(s)
      中山敬一
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 次世代プロテオミクスによって明らかとなったがん代謝ダイナミクス:第二のワールブルグ効果の発見.2019

    • Author(s)
      中山 敬一
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] A metabolic shift in nitrogen flux from glutamine contributes to malignant progression of cancer: Discovery of the SECOND Warburg effect.2019

    • Author(s)
      Nakayama, K. I., Kodama, M., Matsumoto, M.
    • Organizer
      Cell Symposia: Hallmarks of Cancer
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 次世代プロテオミクスが拓くがん研究の新時代:第二のワールブルグ効果の発見.2019

    • Author(s)
      中山 敬一
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 近未来のがん研究:オミクスと人工知能によるデータドリブン科学の時代.2019

    • Author(s)
      中山 敬一
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Next-generation proteomics unveils a global landscape of cancer metabolism: Discovery of the "second" Warburg effect.2019

    • Author(s)
      Nakayama, K. I.
    • Organizer
      RIKEN-Max Planck Joint Research Center for Systems Chemical Biology 7th Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] がん代謝における窒素利用シフト:第二のワールブルグ効果の発見.2019

    • Author(s)
      中山 敬一
    • Organizer
      第7回がんと代謝研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Next-generation proteomics unveils a global landscape of cancer metabolism: Discovery of the "second" Warburg effect2019

    • Author(s)
      Keiichi I. Nakayama
    • Organizer
      11th AACR-JCA Joint Conference on Breakthroughs in Cancer Research: Biology to Precision Medicine
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] c-Mycによって統合されるがん代謝ネットワークの全貌2018

    • Author(s)
      中山敬一
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 転移巣にTAMを呼び寄せるメカニズムとそれを阻害する既存薬2018

    • Author(s)
      中山敬一
    • Organizer
      第16回がんとハイポキシア研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] がん幹細胞における細胞周期制御2018

    • Author(s)
      中山敬一
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 人工知能を用いたスコアシステムは乳がん患者の予後を正確に予測する2018

    • Author(s)
      中山敬一
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] グルタミンからの窒素流束の代謝シフトはがん悪性化に必要である:第二のワールブルグ効果の発見2018

    • Author(s)
      中山敬一
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 鉄代謝制御を司るユビキチンシステムと疾患2018

    • Author(s)
      中山敬一
    • Organizer
      第42回鉄バイオサイエンス学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Book] 実験医学2021年7月号2021

    • Author(s)
      中山敬一
    • Total Pages
      129
    • Publisher
      羊土社
    • ISBN
      9784758125451
    • Related Report
      2021 Annual Research Report
  • [Remarks] 九州大学生体防御医学研究所分子医科学分野

    • URL

      https://www.bioreg.kyushu-u.ac.jp/saibou/index.html

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Remarks] 九州大学生体防御医学研究所分子医科学分野

    • URL

      http://www.bioreg.kyushu-u.ac.jp/saibou/index.html

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 相互作用推定方法、相互作用推定装置および相互作用推定プログラム2021

    • Inventor(s)
      中山敬一, 清水秀幸
    • Industrial Property Rights Holder
      国立大学法人九州大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-091667
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] 被検体に生じるイベントを予測するための判別器の生成方法、及び前記判別器を用いた被検体の層別化方法2019

    • Inventor(s)
      中山敬一、清水秀幸
    • Industrial Property Rights Holder
      国立大学法人九州大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 被検体に生じるイベントを予測するための判別器の生成方法、及び前記判別器を用いた被検体の層別化方法2018

    • Inventor(s)
      中山敬一、清水秀幸
    • Industrial Property Rights Holder
      国立大学法人九州大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-157870
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] FOXK1阻害剤を含有する組成物及びFOXK1阻害作用を有する候補物質のスクリーニング方法2018

    • Inventor(s)
      中山敬一
    • Industrial Property Rights Holder
      国立大学法人九州大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-185599
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-25   Modified: 2022-12-28  

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