Course

生化学・分子遺伝学

Course introduction

講座紹介

分子・機能領域
生化学・分子遺伝学（旧名称：医化学第二講座）

がん細胞や血管細胞（特に血管内皮細胞）の分裂・増殖を人為的に制御する手法の開発と臨床応用を目指しています。

【講座問い合わせ先】
分子・機能領域　生化学・分子遺伝学　〒791-0295愛媛県東温市志津川454
TEL：089-960-5254 / FAX：089-960-5256
公式HP https://www.m.ehime-u.ac.jp/school/biochem2/

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Course introduction

研究内容

がん細胞や血管細胞（特に血管内皮細胞）の分裂・増殖を人為的に制御する手法の開発と臨床応用を目指し、２つの分子カテゴリーで研究を進めています。

  • 1)  DNA障害型抗癌剤の感受性を決めるSLFN11の機能解析と臨床応用
  • 2) ユビキチンリガーゼCRL3による血管内皮細胞機能制御機構の解析
  • 3) DNA複製ストレス制御因子 SPOPの分子機構解析とがん治療応用
  • 4) 受容体型チロシンキナーゼ HERの新規制御方の開発とがん治療応用
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Course introduction

主な実績

  • Fujiwara K, Maekawa M, Iimori Y, Ogawa A, Urano T, Kono N, Takeda H, Higashiyama S, Arita M, Murai J.　The crucial role of single-stranded DNA binding in enhancing sensitivity to DNA-damaging agents for Schlafen 11 and Schlafen 13.　iScience. 2023 Nov 23;26(12):108529. doi: 10.1016/j.isci.2023.108529.

 

  • Murai J, Pommier Y.BRCAness, Homologous Recombination Deficiencies, and Synthetic Lethality.Cancer Res. 2023 Apr 14;83(8):1173-1174. doi: 10.1158/0008-5472.CAN-23-0628.PMID: 37057596

 

  • Murai Y, Jo U, Murai J, Fukuda S, Takebe N, Pommier Y.  Schlafen 11 expression in human acute leukemia cells with gain-of-function mutations in the interferon-JAK signaling pathway. iScience. 2021 Sep 25;24(10):103173. doi: 10.1016/j.isci.2021.103173.

 

  • Jo U, Murai Y, Chakka S, Chen L, Cheng K, Murai J, Saha LK, Miller Jenkins LM, Pommier Y. SLFN11 promotes CDT1 degradation by CUL4 in response to replicative DNA damage, while its absence leads to synthetic lethality with ATR/CHK1 inhibitors. Proc Natl Acad Sci U S A. 2021 Feb 9;118(6):e2015654118. doi: 10.1073/pnas.2015654118.

 

  • Tanaka M, Nakamura S, Sakaue T, Yamamoto T, Maekawa M, Nishinaka A, Yasuda H, Yunoki K, Sato Y, Sawa M, Yoshino K, Shimazawa M, Hatano M, Tokuhisa T, Higashiyama S, Hara H.　BCL6B Contributes to Ocular Vascular Diseases via Notch Signal Silencing.　Arterioscler Thromb Vasc Biol. 2023 Jun;43(6):927-942. doi: 10.1161/ATVBAHA.123.318987.

 

  • Nishiyama K, Maekawa M, Nakagita T, Nakayama J, Kiyoi T, Chosei M, Murakami A, Kamei Y, Takeda H, Takada Y, Higashiyama S.　CNKSR1 serves as a scaffold to activate an EGFR phosphatase via exclusive interaction with RhoB-GTP.Life Sci Alliance. 2021 Jun 29;4(9):e202101095. doi: 10.26508/lsa.202101095.

 

  • Watanabe R, Maekawa M, Hieda M, Taguchi T, Miura N, Kikugawa T, Saika T, Higashiyama S. SPOP is essential for DNA-protein cross-link repair in prostate cancer cells: SPOP-dependent removal of topoisomerase 2A from the topoisomerase 2A-DNA cleavage complex. Mol Biol Cell. 2020 Mar 15;31(6):478-490. doi: 10.1091/mbc.E19-08-0456.

 

  • Murai J, Zhang H, Pongor L, Tang SW, Jo U, Moribe F, Ma Y, Tomita M, Pommier Y. Chromatin Remodeling and Immediate Early Gene Activation by SLFN11 in Response to Replication Stress. Cell Rep. 2020 Mar 24;30(12):4137-4151.e6. doi: 10.1016/j.celrep.2020.02.117.

 

  • Murai J, Pommier Y. Phosphatase 1 Nuclear Targeting Subunit, a Novel DNA Repair Partner of PARP1. Cancer Res. 2019 May 15;79(10):2460-2461. doi: 10.1158/0008-5472.CAN-19-0798.

 

  • Kovačević I, Sakaue T, Majoleé J, Pronk MC, Maekawa M, Geerts D, Fernandez-Borja M,　Higashiyama S, Hordijk PL. The Cullin-3-Rbx1-KCTD10 complex controls endothelial barrier function via K63 ubiquitination of RhoB. J Cell Biol. 2018 Mar 5;217(3):1015-1032. doi: 10.1083/jcb.201606055.

 

  • Thomas A, Murai J, Pommier Y.The evolving landscape of predictive biomarkers of response to PARP inhibitors. J Clin Invest. 2018 May 1;128(5):1727-1730. doi: 10.1172/JCI120388. Epub 2018 Apr 16.

 

  • Murai J, Tang SW, Leo E, Baechler SA, Redon CE, Zhang H, Al Abo M, Rajapakse VN, Nakamura E, Jenkins LMM, Aladjem MI, Pommier Y. SLFN11 Blocks Stressed Replication Forks Independently of ATR.
    Mol Cell. 2018 Feb 1;69(3):371-384.e6. doi: 10.1016/j.molcel.2018.01.012.

 

  • Bruno PM, Liu Y, Park GY, Murai J, Koch CE, Eisen TJ, Pritchard JR, Pommier Y, Lippard SJ, Hemann MT. A subset of platinum-containing chemotherapeutic agents kills cells by inducing ribosome biogenesis stress.Nat Med. 2017 Apr;23(4):461-471. doi: 10.1038/nm.4291. Epub 2017 Feb 27.

 

  • Fukuda S, Nishida-Fukuda H, Nanba D, Nakashiro K, Nakayama H, Kubota H, Higashiyama S. Reversible interconversion and maintenance of mammary epithelial cell characteristics by the ligand-regulated EGFR system. Sci Rep. 2016 Feb 2;6:20209. doi: 10.1038/srep20209.

 

  • Nanba D, Toki F, Tate S, Imai M, Matsushita N, Shiraishi K, Sayama K, Toki H, Higashiyama S, Barrandon Y. Cell motion predicts human epidermal stemness.　J Cell Biol. 2015 Apr 27;209(2):305-15. doi: 10.1083/jcb.201409024.

 

  • Nanba D, Toki F, Matsushita N, Matsushita S, Higashiyama S, Barrandon Y. Actin filament dynamics impacts keratinocyte stem cell maintenance. EMBO Mol Med. 2013 Apr;5(4):640-53. doi: 10.1002/emmm.201201839.

 

  • Ohnuki H, Inoue H, Takemori N, Nakayama H, Sakaue T, Fukuda S, Miwa D, Nishiwaki E, Hatano M, Tokuhisa T, Endo Y, Nose M, Higashiyama S. BAZF, a novel component of cullin3-based E3 ligase complex, mediates VEGFR and Notch cross-signaling in angiogenesis. Blood. 2012 Mar 15;119(11):2688-98. doi: 10.1182/blood-2011-03-345306.

 

  • Inoue A, Ishiguro J, Kitamura H, Arima N, Okutani M, Shuto A, Higashiyama S, Ohwada T, Arai H, Makide K, Aoki J. TGFα shedding assay: an accurate and versatile method for detecting GPCR activation. Nat Methods. 2012 Oct;9(10):1021-9. doi: 10.1038/nmeth.2172.

 

  • Sahin U, Weskamp G, Kelly K, Zhou HM, Higashiyama S, Peschon J, Hartmann D, Saftig P, Blobel CP. Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands. J Cell Biol. 2004 Mar 1;164(5):769-79. doi: 10.1083/jcb.200307137.

 

  • Nanba D, Mammoto A, Hashimoto K, Higashiyama S. Proteolytic release of the carboxy-terminal fragment of proHB-EGF causes nuclear export of PLZF. J Cell Biol. 2003 Nov 10;163(3):489-502. doi: 10.1083/jcb.200303017.

 

  • Asakura M, Kitakaze M, Takashima S, Liao Y, Ishikura F, Yoshinaka T, Ohmoto H, Node K, Yoshino K, Ishiguro H, Asanuma H, Sanada S, Matsumura Y, Takeda H, Beppu S, Tada M, Hori M, Higashiyama S. Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: metalloproteinase inhibitors as a new therapy. Nat Med. 2002 Jan;8(1):35-40. doi: 10.1038/nm0102-35.

 

  • Higashiyama S, Abraham JA, Miller J, Fiddes JC, Klagsbrun M. A heparin-binding growth factor secreted by macrophage-like cells that is related to EGF. Science. 1991 Feb 22;251(4996):936-9. doi: 10.1126/science.1840698.
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Staff introduction

スタッフ紹介

スタッフ紹介

  • 東山 繁樹 (教授)
  • 村井　純子 (准教授)
  • 田手 壮太 (助教)
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Department of Medicine

医学専攻・医学科>

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