Simizu, Siro

写真a

Affiliation

Faculty of Science and Technology, Department of Applied Chemistry (Yagami)

Position

Professor

E-mail Address

E-mail address

Related Websites

Profile Summary 【 Display / hide

  • ケミカルバイオロジー、糖質科学、がん生物学を中心に研究を行っています。講義では化学の視点で生物学を理解できるように取り組んでいます。

Academic Background 【 Display / hide

  • 1993.03

    Keio University, Faculty of Science and Engineering, Department of Applied Chemistry

    University, Graduated

  • 1998.03

    Keio University, Graduate School, Division of Science and Engineering

    Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide

  • Ph.D., Keio University, Coursework, 1998.03

 

Research Areas 【 Display / hide

  • Bio-related chemistry

  • Molecular biology

Research Keywords 【 Display / hide

  • Cancer cell biology

  • Chemical Biology

  • Glycoscience

 

Books 【 Display / hide

  • 実験医学

    宮崎 功、奥村 英夫、清水 史郎、長田 裕之, 2011

    Scope: 79-83

  • 化学と工業

    叶 直樹、清水 史郎, 2011

    Scope: 37-39

Papers 【 Display / hide

  • C-mannosylation of R-spondin2 activates Wnt/β-catenin signaling and migration activity in human tumor cells

    Mizuta, H., Kuga, K., Suzuki, T., Niwa, Y., Dohmae, N. & Simizu, S.

    Int. J. Oncol.  2019

    Research paper (scientific journal), Joint Work, Accepted

  • Unified total synthesis of madangamine alkaloids

    Suto, T., Yanagita, Y., Nagashima, Y., Takikawa, S., Kurosu, Y., Matsuo, N., Miura, K., Simizu, S., Sato, T. & Chida, N.

    Bull. Chem. Soc. Jpn.  92   545 - 571 2019

    Research paper (scientific journal), Joint Work, Accepted

  • Integrin β1 is an essential factor in vasculogenic mimicry of human cancer cells

    Kawahara R., Niwa Y., Simizu S.

    Cancer Science (Cancer Science)  109 ( 8 ) 2490 - 2496 2018.08

    ISSN  13479032

     View Summary

    © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. Vasculogenic mimicry (VM) formation by cancer cells is known to play a crucial role in tumor progression, but its detailed mechanism is unclear. In the present study, we focused on integrin β1 (ITGB1) and assessed the role of ITGB1 in VM formation. We used in vitro methods to seed cancer cells on Matrigel to evaluate the capability of VM formation. We carried out ITGB1 gene deletion using the CRISPR/Cas9 system, and these ITGB1-knockout cells did not show a VM-like network formation. Further, reintroduction of ITGB1 rescued VM-like network formation in ITGB1-knockout cells. In conclusion, ITGB1 is a critical factor in VM of human cancer cells, and inhibition of ITGB1 may be a novel therapeutic approach for malignant cancer.

  • Regulation of granulocyte colony-stimulating factor receptor-mediated granulocytic differentiation by C-mannosylation

    Otani K., Niwa Y., Suzuki T., Sato N., Sasazawa Y., Dohmae N., Simizu S.

    Biochemical and Biophysical Research Communications (Biochemical and Biophysical Research Communications)  498 ( 3 ) 466 - 472 2018.04

    ISSN  0006291X

     View Summary

    © 2018 Elsevier Inc. Granulocyte colony-stimulating factor (G-CSF) receptor (G-CSFR) is a type I cytokine receptor which is involved in hematopoietic cell maturation. G-CSFR has three putative C-mannosylation sites at W253, W318, and W446; however, it is not elucidated whether G-CSFR is C-mannosylated or not. In this study, we first demonstrated that G-CSFR was C-mannosylated at only W318. We also revealed that C-mannosylation of G-CSFR affects G-CSF-dependent downstream signaling through changing ligand binding capability but not cell surface localization. Moreover, C-mannosylation of G-CSFR was functional and regulated granulocytic differentiation in myeloid 32D cells. In conclusion, we found that G-CSFR is C-mannosylated at W318 and that this C-mannosylation has role(s) for myeloid cell differentiation through regulating downstream signaling.

  • Therapeutic activity of plant-derived alkaloid conophylline on metabolic syndrome and neurodegenerative disease models

    Umezawa K., Kojima I., Simizu S., Lin Y., Fukatsu H., Koide N., Nakade Y., Yoneda M.

    Human Cell (Human Cell)  31 ( 2 ) 95 - 101 2018.04

    ISSN  09147470

     View Summary

    © 2017, Japan Human Cell Society and Springer Japan KK, part of Springer Nature. Increasing metabolic syndromes including type-2 diabetes mellitus, obesity, and steatohepatitis are serious problems in most countries in the world. Neurodegenerative diseases such as Alzheimer, Parkinson’s, and Huntington’s diseases are increasing in many countries. However, therapy for these diseases is not sufficient yet. Thus, effective chemotherapy for these diseases is being expected. Conophylline is an alkaloid isolated from the leaves of Ervatamia microphylla and related plants. It was found to induce beta-cell differentiation in the precursor pancreatic cells. Oral administration of this compound ameliorated type-2 diabetes mellitus model in mice and rats. Later, fibrosis of the pancreatic islets was found to be greatly reduced by conophylline in the pancreatic islets. It also inhibited chemically induced liver cirrhosis. Further study indicated that conophylline inhibited non-alcoholic steatohepatitis in the model mice. On the one hand, loss of autophagy often causes protein aggregation to give neural cell death. Conophylline was found to activate autophagy in cultured neural cells. Activation of autophagy ameliorated cellular models of Parkinson’s and Huntington’s diseases. Thus, conophylline is likely to be useful for the development of chemotherapy for metabolic and neurodegenerative diseases.

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • C-Mannosylation: Previous studies and future research perspectives

    Niwa Y., Simizu S.

    Trends in Glycoscience and Glycotechnology (Trends in Glycoscience and Glycotechnology)  30 ( 177 ) E231 - E238 2018.11

    ISSN  09157352

     View Summary

    © 2018 FCCA (Forum: Carbohydrates Coming of Age). C-linked glycosylation, one of the protein glycosylations, is a unique type of glycosylation in which an α-mannose is attached to the indole C2 carbon of a tryptophan residue via a C–C linkage and is so named C-mannosylation. C-mannosylation is enzymati-cally catalyzed in the endoplasmic reticulum (ER) lumen, and the N-terminal side Trp residue of the consensus amino acid sequence Trp-Xaa-Xaa-Trp/Cys (Xaa represents any amino acid) is often C-mannosylated. It has been reported that about 30 proteins are C-mannosylated, and the functions of C-mannosylation are becoming clear. In 2013, C. elegans dumpy-19 (dpy-19) was identified as a C-mannosyltransferase, and we revealed that DPY19L3, one of the human homologs of dpy-19, has similar activity in 2016. In this review, we describe previous studies about C-mannosylation, including our results and future research perspectives.

  • C-Mannosylation: Previous studies and future research perspectives

    Niwa Y., Simizu S.

    Trends in Glycoscience and Glycotechnology (Trends in Glycoscience and Glycotechnology)  30 ( 177 )  2018.11

    ISSN  09157352

     View Summary

    © 2018 FCCA (Forum: Carbohydrates Coming of Age). C-linked glycosylation, one of the protein glycosylations, is a unique type of glycosylation in which an α-mannose is attached to the indole C2 carbon of a tryptophan residue via a C–C linkage and is so named C-mannosylation. C-mannosylation is enzymati-cally catalyzed in the endoplasmic reticulum (ER) lumen, and the N-terminal side Trp residue of the consensus amino acid sequence Trp-Xaa-Xaa-Trp/Cys (Xaa represents any amino acid) is often C-mannosylated. It has been reported that about 30 proteins are C-mannosylated, and the functions of C-mannosylation are becoming clear. In 2013, C. elegans dumpy-19 (dpy-19) was identified as a C-mannosyltransferase, and we revealed that DPY19L3, one of the human homologs of dpy-19, has similar activity in 2016. In this review, we describe previous studies about C-mannosylation, including our results and future research perspectives.

Presentations 【 Display / hide

  • R-spondin1 におけるリン酸化の機能解析

    西谷 拓海, 鈴木 健裕, 丹羽 祐貴, 三浦 一輝, 堂前 直, 清水 史郎

    日本農芸化学会関東支部会2018年度大会 (千葉) , 2018.10, Poster (general)

  • Vibsanin A誘導体の生物活性評価および標的分子の同定

    三浦 一輝、松木 渉、高尾 賢一、清水 史郎

    日本農芸化学会関東支部会2018年度大会  (千葉) , 2018.10, Poster (general)

  • ヒトC型糖転移酵素DPY19L3のプロモーター解析

    吉本 哲、三浦 一輝、清水 史郎

    日本農芸化学会関東支部会2018年度大会  (千葉) , 2018.10, Poster (general)

  • トポロジー解析によるDPY19L1のC-mannosyltransferase活性中心の探索

    横山 典弘, 柳原 凌太郎, 三浦 一輝, 丹羽 祐貴, 清水 史郎

    日本農芸化学会関東支部会2018年度大会 (千葉) , 2018.10, Poster (general)

  • C-mannosylation-基質と酵素の探索

    清水 史郎

    日本農芸化学会中部支部 第183回例会 (名古屋) , 2018.09, Symposium, Workshop, Panelist (nomination)

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 新たなC型糖修飾責任酵素の同定と基質タンパク質の解析

    2018.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 清水 史郎, Grant-in-Aid for Scientific Research (C), Principal Investigator

Awards 【 Display / hide

  • 日本がん転移学会 研究奨励賞

    SIMIZU Siro, 2012.07, 日本がん転移学会, ケミカルバイオロジーによる転移関連分子の理解と制御

    Type of Award: Awards of National Conference, Council and Symposium

  • B.B.B.論文賞

    MIYAZAKI Isao, SIMIZU Siro, ICHIMIYA Harumi, KAWATANI Makoto, OSADA Hiroyuki, 2009.03, 日本農芸化学会, Robust and systematic drug screening method using chemical arrays and the protein library: identification of novel inhibitors of carbonic anhydrase II

    Type of Award: Awards of National Conference, Council and Symposium

  • 日本癌学会奨励賞

    SIMIZU Siro, 2004.10, 日本癌学会, 薬剤耐性・転移に関与するがん分子標的の機能解析

    Type of Award: Awards of National Conference, Council and Symposium

 

Courses Taught 【 Display / hide

  • BACHELOR'S THESIS

    2020

  • BIOORGANIC CHEMISTRY

    2020

  • SEMINAR IN APPLIED CHEMISTRY

    2020

  • MICROBIOLOGY

    2020

  • LABORATORIES IN APPLIED CHEMISTRY D

    2020

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Memberships in Academic Societies 【 Display / hide

  • The Japanese Society of Carbohydrate Research, 

    2015
    -
    Present
  • 日本がん分子標的治療学会, 

    2009
    -
    Present
  • 日本ケミカルバイオロジー学会, 

    2008
    -
    Present
  • 日本がん転移学会, 

    2006
    -
    Present
  • 日本癌学会, 

    1992
    -
    Present

Committee Experiences 【 Display / hide

  • 2015
    -
    Present

    Member, 日本がん転移学会

  • 2009
    -
    Present

    Board of Councillors, 日本がん分子標的治療学会

  • 2008
    -
    Present

    Member, 日本ケミカルバイオロジー学会

  • 1992
    -
    Present

    Member, 日本癌学会