Ishida, Hanako



Faculty of Pharmacy, Department of Pharmaceutical Sciences (Shiba-Kyoritsu)


Research Associate/Assistant Professor/Instructor

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Career 【 Display / hide

  • 2022.04

    Faculty of Pharmacy, Keio University, Assistant professor

  • 2014.04

    Graduate School of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, The University of Tokyo, project researcher

  • 2011.10

    Graduate School of Engineering, Osaka University, technical assistant

  • 2009.02

    Chiome Bioscience Inc.

  • 2006.04

    International College of Arts and Sciences, Yokohama City University, technical assistant

Academic Background 【 Display / hide

  • 2004.04

    Tottori University, Faculty of Agriculture, Department of Agriculture

    Graduate School, Completed, Master's course

  • 2000.04

    Tokyo University of Agriculture, Faculty of Agriculture, Department of Agriculture

    University, Graduated

Academic Degrees 【 Display / hide

  • 博士(薬科学), The University of Tokyo, Dissertation, 2019.03

    Structural biology of activation mechanism of innate immune receptor TLR9


Papers 【 Display / hide

  • Structure of the bile acid transporter and HBV receptor NTCP

    Asami J., Kimura K.T., Fujita-Fujiharu Y., Ishida H., Zhang Z., Nomura Y., Liu K., Uemura T., Sato Y., Ono M., Yamamoto M., Noda T., Shigematsu H., Drew D., Iwata S., Shimizu T., Nomura N., Ohto U.

    Nature (Nature)  606 ( 7916 ) 1021 - 1026 2022.06

    Research paper (scientific journal), Accepted,  ISSN  00280836

     View Summary

    Chronic infection with hepatitis B virus (HBV) affects more than 290 million people worldwide, is a major cause of cirrhosis and hepatocellular carcinoma, and results in an estimated 820,000 deaths annually1,2. For HBV infection to be established, a molecular interaction is required between the large glycoproteins of the virus envelope (known as LHBs) and the host entry receptor sodium taurocholate co-transporting polypeptide (NTCP), a sodium-dependent bile acid transporter from the blood to hepatocytes3. However, the molecular basis for the virus–transporter interaction is poorly understood. Here we report the cryo-electron microscopy structures of human, bovine and rat NTCPs in the apo state, which reveal the presence of a tunnel across the membrane and a possible transport route for the substrate. Moreover, the cryo-electron microscopy structure of human NTCP in the presence of the myristoylated preS1 domain of LHBs, together with mutation and transport assays, suggest a binding mode in which preS1 and the substrate compete for the extracellular opening of the tunnel in NTCP. Our preS1 domain interaction analysis enables a mechanistic interpretation of naturally occurring HBV-insusceptible mutations in human NTCP. Together, our findings provide a structural framework for HBV recognition and a mechanistic understanding of sodium-dependent bile acid translocation by mammalian NTCPs.

  • Structural basis for the oligomerization-mediated regulation of NLRP3 inflammasome activation

    Ohto U., Kamitsukasa Y., Ishida H., Zhangami K., Hirama C., Maekawa S., Shimizu T. Z., Murak

    Proceedings of the National Academy of Sciences of the United States of America (Proceedings of the National Academy of Sciences of the United States of America)  119 ( 11 ) e2121353119 2022.03

    Research paper (scientific journal), Accepted,  ISSN  00278424

     View Summary

    The nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) responds to a vast variety of stimuli, and activated NLRP3 forms an inflammasome, which in turn is associated with conditions such as atherosclerosis, Alzheimer's disease, and diabetes. A multilayered regulatory mechanism ensures proper NLRP3 inflammasome activation, although the structural basis for this process remains unclear. This study aimed to investigate the cryo-electron microscopy structure of the dodecameric form of full-length NLRP3 bound to the clinically relevant NLRP3-specific inhibitor MCC950. The inhibitor binds to the cavity distinct from the nucleotide binding site in the NACHT domain and stabilizes the closed conformation of NLRP3. The barrel-shaped dodecamer composed of the inactive form of NLRP3 is formed mainly through LRR-LRR interactions on the lateral side, and the highly positively charged top and bottom sides composed of NACHT domains provide a scaffold for membrane association. The cryo-electron microscopy structure suggests that oligomerization of NLRP3 is necessary for its membrane association; it is subsequently disrupted for activation, hence serving as a key player in controlling the spatiotemporal NLRP3 inflammasome activation. These findings are expected to contribute to the development of drugs targeting NLRP3 in future.

  • Cryo-EM structures of Toll-like receptors in complex with UNC93B1

    Ishida H., Asami J., Zhang Z., Nishizawa T., Shigematsu H., Ohto U., Shimizu T.

    Nature Structural and Molecular Biology (Nature Structural and Molecular Biology)  28 ( 2 ) 173 - 180 2021.02

    Research paper (scientific journal), Accepted,  ISSN  15459993

     View Summary

    Nucleic acid–sensing Toll-like receptors (TLRs) play a pivotal role in innate immunity by recognizing foreign DNA and RNA. Compartmentalization of these TLRs in the endosome limits their activation by self-derived nucleic acids and reduces the possibility of autoimmune reactions. Although chaperone Unc-93 homolog B1, TLR signaling regulator (UNC93B1) is indispensable for the trafficking of TLRs from the endoplasmic reticulum to the endosome, mechanisms of UNC93B1-mediated TLR regulation remain largely unknown. Here, we report two cryo-EM structures of human and mouse TLR3–UNC93B1 complexes and a human TLR7–UNC93B1 complex. UNC93B1 exhibits structural similarity to the major facilitator superfamily transporters. Both TLRs interact with the UNC93B1 amino-terminal six-helix bundle through their transmembrane and luminal juxtamembrane regions, but the complexes of TLR3 and TLR7 with UNC93B1 differ in their oligomerization state. The structural information provided here should aid in designing compounds to combat autoimmune diseases.

  • The effect of anesthetics on toll like receptor 9.

    Koutsogiannaki S, Bu W, Hou L, Shibamura-Fujiogi M, Ishida H, Ohto U, Eckenhoff RG, Yuki K

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology 34 ( 11 ) 14645 - 14654 2020.11

    Research paper (scientific journal), Accepted,  ISSN  0892-6638

  • Homeostatic and pathogenic roles of GM3 ganglioside molecular species in TLR4 signaling in obesity.

    Kanoh H, Nitta T, Go S, Inamori KI, Veillon L, Nihei W, Fujii M, Kabayama K, Shimoyama A, Fukase K, Ohto U, Shimizu T, Watanabe T, Shindo H, Aoki S, Sato K, Nagasaki M, Yatomi Y, Komura N, Ando H, Ishida H, Kiso M, Natori Y, Yoshimura Y, Zonca A, Cattaneo A, Letizia M, Ciampa M, Mauri L, Prinetti A, Sonnino S, Suzuki A, Inokuchi JI

    The EMBO journal 39 ( 12 ) e101732 2020.06

    Research paper (scientific journal), Accepted,  ISSN  0261-4189

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Reviews, Commentaries, etc. 【 Display / hide

Presentations 【 Display / hide

  • Structural basis of the activation and trafficking mechanisms of nucleic acid-sensing TLR

    Hanako Ishida

    Molecular Biology Society of Japan (神戸ポートアイランド) , 


    Oral presentation (invited, special), 日本分子生物学会年会事務局


Courses Taught 【 Display / hide











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