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Affiliation |
Faculty of Pharmaceutical Sciences Department of Pharmaceutical Sciences |
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Title |
Associate Professor |
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External Link |
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WATANABE Chie
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Degree 【 display / non-display 】
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医学博士 ( 2002.03 大阪大学 )
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薬学修士 ( 1998.03 富山医科薬科大学 )
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薬学学士 ( 1996.03 富山医科薬科大学 )
Research Areas 【 display / non-display 】
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Life Science / Clinical pharmacy
From School 【 display / non-display 】
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Toyama Medical and Pharmaceutical University Faculty of Pharmaceutical Science Graduated
1992.04 - 1996.03
Country：Japan
Studying abroad experiences 【 display / non-display 】
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2005.04 - 2008.11 University of Washington Senior Fellow
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2003.11 - 2005.03 University of Washington
Employment Record in Research 【 display / non-display 】
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Josai University Faculty of Pharmaceutical Sciences Department of Pharmaceutical Sciences Associate Professor
2018.04
External Career 【 display / non-display 】
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Osaka Ohtani University Assistant Professor
2014.04 - 2018.03
Country：Japan
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Osaka Ohtani University
2012.10 - 2013.12
Country：Japan
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ワシントン大学 医学部 研究員
2005.04 - 2008.11
Country：United States
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ワシントン大学 医学部 日本学術振興会特別研究員
2003.11 - 2005.03
Country：United States
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Osaka University Special researcher of the Japan Society for the Promotion of Science
2002.04 - 2003.10
Country：Japan
Professional Memberships 【 display / non-display 】
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日本リンパ学会
2018.10
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コントロールリリース学会 (Controlled Release Society)
2016.04
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遺伝子・デリバリー研究会
2016.04
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日本DDS学会
2014.04
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日本薬学会
2014.04
Research Career 【 display / non-display 】
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再発性悪性リンパ腫の完全根治を目指したリンパ移行性腫瘍標的型核酸製剤の創製
Grant-in-Aid for Scientific Research
Project Year： 2021.04 -
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核酸医薬品へのパラダイムシフトを加速する経口核酸送達システムの開発研究
Grant-in-Aid for Scientific Research
Project Year： 2018.04 -
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三次元腸管粘膜再構築モデルの作製と核酸製剤を用いた基礎的評価
Grant-in-Aid for Scientific Research
Project Year： 2014.04 -
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画期的な新規核酸医薬の分子技術の創出
JST Basic Research Programs (Core Research for Evolutional Science and Technology :CREST)
Project Year： 2012.10 - 2018.03
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肝臓に対する新規DDSを活用した経口遺伝子治療法の開発
Health and Labour Sciences Research Grants
Project Year： 2011.04 - 2012.03
Papers 【 display / non-display 】
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Regulation of B-lineage cells by caspase 6. Reviewed International journal
C. Watanabe, G.L. Shu, N.V. Giltay, E. A. Clark
Immunology and Cell Biology 1 - 11 2018.06
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Wiley
The caspase (Casp) family of proteases regulate both lymphocyte apoptosis and activation. Here, we show that Casp6 regulates early B-cell development. One-week-old Casp6 knockout (Casp6 KO) mice have significantly more splenic B-cell subsets than wild-type (WT) mice. Adult Casp6 KO mice have normal levels of total splenic B cells but have increased numbers of B1a B cells and CD43+ "transitional" or splenic red pulp (RP) B cells. These results suggested that Casp6 may function to control B-cell numbers under nonhomeostatic conditions and during B-cell development. Consistent with this model, reconstitution of B cells was dysregulated in Casp6 KO mice after sublethal irradiation. Furthermore, bone marrow pro-B, pre-B and immature B-cell numbers were significantly higher in 1-week-old Casp6 KO mice than in 1-week-old WT mice. Casp6 KO pro-B cells proliferated more in response to IL-7 than WT pro-B cells, suggesting that Casp6 regulates early B-cell responses to IL-7. Indeed, adult and aged Casp6 KO mice had elevated numbers of IL-7αR+ Sca1+ precursors of common lymphoid progenitors, suggesting Casp6 may help regulate progenitors of B cells and early B-lineage cells. Casp6 regulates B-cell programs both during early development and after antigen stimulation in the periphery.
DOI： 10.1111/imcb.12172
Other Link： https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12172
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Janus microspheres for enhanced enteral drug delivery: Preparation and orientated attachment to a Caco-2 monolayer. Reviewed International journal
Akihiro Matsumoto, Chie Watanabe, Masahiro Murakami
Drug Discoveries & Therapeutics 13 ( 6 ) 343 - 353 2019.12
Authorship：Second author Language：English Publishing type：Research paper (scientific journal) Publisher： International Advancement Center for Medicine & Health Research Co., Ltd.
Conventional oral preparations generally release incorporated drugs omnidirectionally, including into the lumen, leading to a low bioavailability of drugs that are unstable in the gastrointestinal tract. Here, we designed Janus microspheres for efficient mucosal drug delivery as single-sided-release microspheres with the oriented attachment to mucus and evaluated their attachment to and orientation on a Caco-2 (human Caucasian colon adenocarcinoma cell line) monolayer. The microspheres comprised a mucus-oriented hemisphere of an ammonioalkyl methacrylate copolymer and a protective hemisphere of a hard fat. Fluorescein isothiocyanate-dextran with an average molecular weight of 3,000-5,000 Da (FD4) was used as a model hydrophilic drug. A water-in-oil emulsion-type solvent evaporation method was employed for fabrication of the Janus microspheres. The yield of Janus microspheres was found to be dependent on the polymer-to-hard fat ratio, with a maximum yield of over 90% being obtained at a ratio of 1:2, whereas lower and higher ratios resulted in monolithic or star-shaped microspheres. FD4 was specifically localized in the polymeric hemisphere. A cell culture study revealed that the Janus microspheres attached to a Caco-2 monolayer via their polymeric hemispheres with the hard fat hemisphere providing a protective sealing. This may lead to the development of an effective enteral drug delivery system for biomedicines, such as polypeptides and nucleic acids.
Other Link： https://www.jstage.jst.go.jp/article/ddt/13/6/13_2019.01090/_article
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Enteral siRNA delivery technique for therapeutic gene silencing in the liver via the lymphatic route. Reviewed International journal
M.Murakami, K.Nishina, C.Watanabe, K.Yoshida-Tanaka, W.Piao, H.Kuwahara, Y.Horikiri, K.Miyata, N.Nishiyama, K.Kataoka, M.Yoshida, H.Mizusawa, T.Yokota
Scientific Reports 5 17035 - 17047 2015
Authorship：Second author Language：English Publishing type：Research paper (scientific journal)
核酸医薬開発において、世界で初めて、局所注射や静脈注射以外の方法による全身性標的型デリバリーを、ビタミンＥ修飾型siRNAを用いた経腸経リンパデリバリーシステムの開発により成功し、実証した。
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Caspase-6 regulates B cell activation and differentiation into plasma cells. Reviewed International journal
C. Watanabe, G. L. Shu, T. Zheng, R. A. Flavell, E. A. Clark
Journal of Immunology 181 ( 10 ) 8810 - 8819 2008
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
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Regulation of B cell entry into the cell cycle. Invited Reviewed International journal
S. Richards, C, Watanabe, L. Santos, A. Craxton, EA Clark
Immunological Review 224 183 - 200 2008
Authorship：Second author Language：English Publishing type：Research paper (scientific journal)
Books and Other Publications 【 display / non-display 】
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ＤＤＳ先端技術の製剤への応用開発
村上正裕、渡辺知恵（ Role： Joint author , トコフェロール修飾による直腸からの肝標的デリバリー技術）
(株）技術情報協会 2017.08
Language：English Book type：Scholarly book
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接着分子ハンドブック (担当項目：CD40L)
渡辺知恵, 菊谷仁（ Role： Contributor , CD40L）
秀潤社 2000
Responsible for pages：CD40L Language：Japanese Book type：General book, introductory book for general audience
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接着分子ハンドブック (担当項目：CD40)
渡辺知恵, 菊谷仁（ Role： Contributor , CD40）
秀潤社 2000
Responsible for pages：CD40 Language：Japanese Book type：Scholarly book
Misc 【 display / non-display 】
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経口核酸医薬開発へのアプローチ Invited
村上正裕、渡辺知恵
36 ( 14 ) 85(1429) - 91(1435) 2021.12
Authorship：Last author Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
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Can colorectal delivery technology provide a platform for enteral oligonucleotide-based therapeutics? Reviewed International journal
M.Murakami, C.Watanabe
Drug Discoveries & Therapeutics 10 ( 5 ) 273 - 275 2016.11
Authorship：Second author Language：English Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
核酸医薬に基づく治療法の経口剤開発における経腸デリバリーの利点について論じた。
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The mechanisms of immune regulation by semaphorins. Invited
渡辺知恵
細胞工学 21 ( 11 ) 1298 - 1303 2002
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
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Enhanced immune responses in transgenic mice over-expressing truncated and soluble forms of the lymphocyte semaphorin CD100/Sema4D International journal
C. Watanabe, A. Kumanogoh, W. Shi, X. Wang, T. Yasui, M. Ikawa, M. Okabe, K. Yoshida and H. Kikutani
Leucocyte Typing VII 132 - 133 2002
Authorship：Lead author Language：English Publishing type：Article, review, commentary, editorial, etc. (international conference proceedings) Publisher：Oxford University Press Inc.
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Costimulatory signals of CD100 by turning off negative signaling of CD72. Invited
C. Watanabe and A. Kumanogoh
臨床免疫 36 ( 3 ) 359 - 365 2001
Authorship：Lead author Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
Presentations 【 display / non-display 】
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Systemic liver-targeting delivery of a novel DNA/RNA heteroduplex oligonucleotide via an enteral route Invited International conference
Chie Watanabe, Masahiro Murakami
3rd edition of Global Conference on Pharmaceutics and Drug delivery systems Magnus Group Conference
Event date： 2019.06
Language：English Presentation type：Oral presentation (invited, special)
Venue：Paris, France
Since the advent of antisense technology, oligonucleotide drugs have attracted a greater deal of attention as next-generation therapeutics, which can be selectively delivered to their target tissue to obtain effective gene silencing. The production of conventional pharmaceutical preparations considering factors such as the oral and rectal dosage form is an essential step in the development of a wide range of oligonucleotide drugs. However, oligonucleotides are macromolecules that are easily disintegrated by nucleases and as such, are generally poorly absorbed by the intestine. We have recently developed a hepatocyte-specific delivery technique for oligonucleotides via an enteral route. The chemical conjugation of siRNA with alpha-tocopherol utilized chylomicrons, which acted as a specific in vivo carrier to the liver and were formulated as lipid nanoparticles using unsaturated fatty acid as an absorption enhancer. The method demonstrated effective silencing of the targeted mRNA (ApoB) expression in mice in a postprandial state (Murakami, et al, Sci. Rep. 2015). In this talk, we will provide an overview of the concept of our enteral delivery technique and discuss our recent results on the development of a DNA/RNA heteroduplex oligonucleotide (HDO) which was newly prepared as a more specific and potent oligonucleotide drug (Nishina K., et al. Nat. Commun., 2015). We used a tight junction (TJ) modulator as a para-cellular specific permeation enhancer (Takahashi A, et al., Biomaterials, 2012) and demonstrated that the HDO conjugate with alpha-tocopherol specifically delivered to the liver following rectal administration of the enema in mice and suppressed ApoB gene expression, consequently achieved the reduction of plasma triglyceride and cholesterol levels in the model mice with hypercholesterolemia. These findings suggest that our enteral delivery technique via the lymphatic route should be useful for developing a non-invasive conventional preparation for oligonucleotide therapeutics. Applicability of this technology to the other organ-specific oligonucleotide delivery systems using conjugates with different targeting molecules or ligands remains to be investigated.
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Rectal delivery of a novel DNA/RNA heteroduplex antisense oligonucleotide for ApoB improves hypercholesterolemia in a mouse model International conference
C.Watanabe, Y. Cheng, A. Watari, M. Kondoh, K Yagi, S. Obika, K. Yoshida-Tanaka, K. Yoshioka, T. Yokota, M. Murakami
14th US-Japan DDS symposium
Event date： 2017.12
Language：English Presentation type：Oral presentation (general)
Venue：Lahanina, HI, USA
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Liver-specific delivery of a novel DNA/RNA heteroduplex oligonucleotide via enteral routes produced by the combination of alpha-tocopherol conjugation and permeation enhancers. International conference
C. Watanabe, Y.Cheng, A. Watari, M.Kondoh, K. Yagi, Y. Matsumoto, K. Toh, K. Miyata, K. Kataoka, S. Obika, K.Yoshida-Tanaka, K. Nishina. T. Yokota, M. Murakami
Controlled Release Society
Event date： 2016.07
Language：English Presentation type：Oral presentation (general)
Venue：Seattle, Washington, USA
新規ヘテロ核酸を各種タイトジャンクション修飾剤を吸収促進剤として用いてマウス腸管内に投薬した所、経腸デリバリーに成功したことを報告した。
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Combination of Vitamin-E conjugation with lipid nanoparticle formulation as a novel enteral delivery technology for a systemic liver targeting of therapeutic oligonucleotides Invited International conference
C. Watanabe, K. Nishina, T. Yokota, M. Murakami
BIT’s 14th annual congress of international drug discovery science and technology-2016
Event date： 2016.06
Language：English Presentation type：Oral presentation (invited, special)
Venue：韓国
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油脂・ポリマー異方性粒子の形態と薬物分布に関する検討
松本昭博、村尾聡、渡辺知恵、村上正裕
日本薬学会第１３７年会
Event date： 2017.03
Language：Japanese Presentation type：Poster presentation
Venue：仙台、日本
Scientific Research Funds Acquisition Results 【 display / non-display 】
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再発性悪性リンパ腫の完全根治を目指したリンパ移行性腫瘍標的型核酸製剤の創製
Grant number：21K07224 2021.04 - 2023.03
日本学術振興会 科学研究費補助金 2021年度 基盤研究(C)
Authorship：Principal investigator
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変形性膝関節症における再生医療適応の判定基準および治療アルゴリズムの確立
Grant number：22K12893 2022.04 - 2025.03
日本学術振興会 科学研究費補助金 2022年度 基盤研究(C)
松田芳和、安藤祐介
Authorship：Coinvestigator(s)
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多孔性ヤヌス微粒子による経口核酸デリバリーの最適化と吸収過程の局所モデル化の試み
Grant number：22K12828 2022.04 - 2025.03
日本学術振興会 科学研究費補助金 2022年度 基盤研究(C)
松本明博、村上正裕
Authorship：Coinvestigator(s)
Social Activities 【 display / non-display 】
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できる薬剤師のための病態学シリーズ
Role(s)： Lecturer
特定非営利活動法人 医療教育研究所 2020.01
Type：Internet
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Role(s)： Lecturer
株式会社 フロムページ 夢ナビライブ 2020.09
Audience： High school students
Type：Science festival
全国の高校生を対象とし、多数の大学と講師陣が模擬授業を行い、学生の進路決定に役立てるイベントにおいて、薬学とは、「病態学」から「薬剤学」まで、薬の役割、薬学の役割を模擬授業の中で説明し、２日にわたりZOOMによる直接の質疑応答を行った。