Faculty of Pharmaceutical Sciences Department of Pharmaceutical Sciences


Associate Professor

External Link

Degree 【 display / non-display

  • 医学博士 ( 2002.03   大阪大学 )

  • 薬学修士 ( 1998.03   富山医科薬科大学 )

  • 薬学学士 ( 1996.03   富山医科薬科大学 )

Research Areas 【 display / non-display

  • Life Science / Clinical pharmacy

From School 【 display / non-display

  • Toyama Medical and Pharmaceutical University   Faculty of Pharmaceutical Science   Graduated

    1992.04 - 1996.03

      More details


Studying abroad experiences 【 display / non-display

  • 2005.04 - 2008.11   University of Washington   Senior Fellow

  • 2003.11 - 2005.03   University of Washington  

Employment Record in Research 【 display / non-display

  • Josai University   Faculty of Pharmaceutical Sciences   Department of Pharmaceutical Sciences   Associate Professor


External Career 【 display / non-display

  • Osaka Ohtani University   Assistant Professor

    2014.04 - 2018.03

      More details


  • Osaka Ohtani University

    2012.10 - 2013.12

      More details


  • ワシントン大学   医学部   研究員

    2005.04 - 2008.11

      More details

    Country:United States

  • 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

      More details

    Country:United States

  • Osaka University   Special researcher of the Japan Society for the Promotion of Science

    2002.04 - 2003.10

      More details


display all >>

Professional Memberships 【 display / non-display

  • 日本リンパ学会


  • コントロールリリース学会 (Controlled Release Society)


  • 遺伝子・デリバリー研究会


  • 日本薬学会


  • 日本DDS学会


display all >>


Research Career 【 display / non-display

  • 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  -   

  • 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  -   

  • 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  -   

  • 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 

  • 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 

display all >>

Papers 【 display / non-display

  • Caco-2 Cell Sheet Partially Laminated with HT29-MTX Cells as a Novel In Vitro Model of Gut Epithelium Drug Permeability Invited Reviewed International journal

    Yi Cheng, Chie Watanabe, Yusuke Ando, Satoshi Kitaoka, Yuya Egawa, Tomoya Takashima, Akihiro Matsumoto, Masahiro Murakami

    Pharmaceutics   15 ( 9 )   2338   2023.09

     More details

    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.3390/pharmaceutics15092338

  • 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

     More details

    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

  • 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

     More details

    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.

    DOI: 10.5582/ddt.2019.01090


    Other Link: https://www.jstage.jst.go.jp/article/ddt/13/6/13_2019.01090/_article

  • 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

     More details

    Authorship:Second author   Language:English   Publishing type:Research paper (scientific journal)  


  • 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

     More details

    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

display all >>

Books and Other Publications 【 display / non-display

  • 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 

     More details

    Language:English   Book type:Scholarly book

  • 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 

     More details

    Responsible for pages:CD40L   Language:Japanese   Book type:General book, introductory book for general audience

  • 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 

     More details

    Responsible for pages:CD40   Language:Japanese   Book type:Scholarly book

Misc 【 display / non-display

  • 経口核酸医薬開発へのアプローチ Invited


    36 ( 14 )   85(1429) - 91(1435)   2021.12

     More details

    Authorship:Last author   Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • 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

     More details

    Authorship:Second author   Language:English   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  


  • The mechanisms of immune regulation by semaphorins. Invited


    細胞工学   21 ( 11 )   1298 - 1303   2002

     More details

    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • 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

     More details

    Authorship:Lead author   Language:English   Publishing type:Article, review, commentary, editorial, etc. (international conference proceedings)   Publisher:Oxford University Press Inc.  

  • 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

     More details

    Authorship:Lead author   Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

display all >>

Presentations 【 display / non-display

  • 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

     More details

    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.

  • 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 

     More details

    Event date: 2017.12

    Language:English   Presentation type:Oral presentation (general)  

    Venue:Lahanina, HI, USA  

  • 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 

     More details

    Event date: 2016.07

    Language:English   Presentation type:Oral presentation (general)  

    Venue:Seattle, Washington, USA  


  • 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 

     More details

    Event date: 2016.06

    Language:English   Presentation type:Oral presentation (invited, special)  


  • 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



     More details

    Event date: 2017.03

    Language:Japanese   Presentation type:Poster presentation  


Scientific Research Funds Acquisition Results 【 display / non-display

  • 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)

      More details

    Authorship:Principal investigator 

  • 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)


      More details


  • 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)


      More details



Social Activities 【 display / non-display

  • 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

     More details


  • 夢ナビ

    Role(s): Lecturer

    株式会社 フロムページ  夢ナビライブ  2020.09

     More details

    Audience: High school students

    Type:Science festival