Personal data

Professor, Division of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo (IMSUT)
Director, International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo (IMSUT)
Guest professor, Laboratory of Vaccine Science, Immunology Frontier Research Center (IFReC), Osaka University
E-mail: kenishii@ims.u-tokyo.ac.jp

Business address

• • Division of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo (IMSUT) 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan

SHORT BIO

Prof. Ken Ishii is currently a professor at Division of Vaccine Science at Department of Microbiology and Immunology at The Institute of Medical Science, The University of Tokyo (IMSUT) as well as a director at International Vaccine Design Center at The Institute of Medical Science, The University of Tokyo (IMSUT) in Japan. Prof. Ishii graduated with a M.D and also obtained a Ph.D. from the School of Medicine, Yokohama City University, Kanagawa, Japan. He is further qualified with his years of experience in vaccine research supported by numerous book and periodical publications since 1994 including 7 years as a Visiting Scientist and IND reviewer at the Office of Vaccine Research and Review (OVRR), Center for Biologics Evaluation and Research (CBER), US Food and Drug Administration (FDA). Based on his carreer, he conducts basic research on innate immune recognition of adjuvants and try to translate into vaccine markets in Japan.

Education history

Research and career history

Awards

Selected Recent Publications

• Kuroda E et al. Inhaled Fine Particles Induce Alveolar Macrophage Death and Interleukin-1α Release to Promote Inducible Bronchus-Associated Lymphoid Tissue Formation. Immunity, 45(6), 1299-1310 (2016).
• Kobiyama K et al. Nonagonistic Dectin-1 ligand transforms CpG into a multitask nanoparticulate TLR9 agonist. Proc Natl Acad Sci U S A, 111(8), 3086-91 (2014).
• Desmet C and Ishii KJ Nucleic acid sensing at the interface between innate and adaptive immunity in vaccination. Nat Rev Immunol, 12(7), 479-91 (2012).
• Marichal T et al. DNA released from dying host cells mediates aluminum adjuvant activity. Nat Med, 17(8), 996-1002 (2011).
• Koyama S, et al. Plasmacytoid dendritic cells delineate immunogenicity of influenza vaccine subtypes. Sci Transl Med, 2(25), 25ra24 (2010).
• Ishii KJ et al. TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines. Nature, 451(7179), 725-9 (2008).

Books

• Ishii KJ and Tang CK (Editor in chief) “Biological DNA Sensor: The Impact of Nucleic Acids on Diseases and Vaccinology” ELSEVIER, 2013

Guide lines

• Guideline for Nonclinical Studies of Preventive Vaccines for Infectious Diseases issued by ministry of health, Japan. 2010. (co-PI of the project and author)
• WHO Guidelines on the Nonclinical Evaluation of Vaccine Adjuvants and Adjuvanted Vaccines 2013 (under revision) (External advisor and author)

Editorial activities

• Editor; Associate Editor:J.Immunol., Vaccines, Front. Immunol., NPJ Vaccines, Human Vaccine & Immunother.
• Advisory board for EBioMedicine, Oncotarget

Education history

Professional Societies (Organizer, Director excluding membership):

Other activities:

RECOGNITION

Honors and Awards:

Education

Research and career history

Selected publication

• Nishio J, Negishi H, Yasui-Kato M, Miki S, Miyanaga K, Aoki K, Mizusawa T, Ueno M, Ainai A, Muratani M, Hangai S, Yanai H, Hasegawa H, Ishii Y, Tanji Y, Taniguchi T. Identification and characterization of a novel Enterococcus bacteriophage with potential to ameliorate murine colitis. Sci Rep. 2021;11(1):20231.
• Negishi H, Endo N, Nakajima Y, Nishiyama T, Tabunoki Y, Nishio J, Koshiba R, Matsuda A, Matsuki K, Okamura T, Negishi-Koga T, Ichinohe T, Takemura S, Ishiwata H, Iemura SI, Natsume T, Abe T, Kiyonari H, Doi T, Hangai S, Yanai H, Fujio K, Yamamoto K, Taniguchi T. Identification of U11snRNA as an endogenous agonist of TLR7-mediated immune pathogenesis. Proc Natl Acad Sci U S A. 2019 ;116(47):23653-23661.
• Kimura Y, Negishi H, Matsuda A, Endo N, Hangai S, Inoue A, Nishio J, Taniguchi T, Yanai H.　A novel chemical compound SINCRO with dual function in the STING-type I interferon and tumor cell death pathways. Cancer science 2018 109(9):2687-2696.
• Sarashina-Kida H, Negishi H, Nishio J, Suda W, Nakajima Y, Yasui-Kato M, Iwaisako K, Kang S, Endo N, Yanai H, Asagiri M, Kida H, Hattori M, Kumanogoh A, Taniguchi T. Gallbladder-derived surfactant protein D regulates gut commensal bacteria for maintaining intestinal homeostasis. Proc Natl Acad Sci U S A. 2017 ;114(38):10178-10183.
• Negishi H, Taniguchi T, Yanai H. The interferon class of cytokines and the IRF transcription factor family. Cold Spring Harb Perspect Biol. 2017 doi: 10.1101/cshperspect.a028423.
• Negishi H, Matsuki K, Endo N, Sarashina H, Miki S, Matsuda A, Fukazawa K, Taguchi-Atarashi N, Ikushima H, Yanai H, Nishio J, Honda K, Fujioka Y, Ohba Y, Noda T, Taniguchi S, Nishida E, Zhang Y, Dong C, Chi H, Flavell FA, Taniguchi T. Beneficial innate signaling interference for anti-bacterial responses by a TLR-mediated enhancement of the MKP-IRF3 axis. Proc Natl Acad Sci U S A. 2013;110(49):19884-19889
• Negishi H, Miki S, Sarashina H, Taguchi-Atarashi N, Nakajima A, Matsuki K, Endo N, Yanai H, Nishio J, Honda K, Taniguchi T. Essential contribution of IRF3 to intestinal homeostasis and microbiota-mediated Tslp gene induction. Proc Natl Acad Sci U S A. 2012 ;109(51):21016-21021.
• Negishi H, Yanai H, Nakajima A, Koshiba R, Atarashi K, Matsuda A, Matsuki K, Miki S, Doi T, Aderem A, Nishio J, Smale S, Honda K, Taniguchi T. Cross-interference of antiviral RLR signaling against TLR pathways modulates antibacterial T cell responses. Nature immunology. 2012 ;13(7):659-666.
• Negishi H, Osawa T, Ogami K, Ouyang X, Sakaguchi S, Koshiba R, Yanai H, Seko Y, Shitara H, Bishop K, Yonekawa H, Tamura T, Kaisho T, Taya C, Taniguchi T, Honda K. A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity. Proc Natl Acad Sci U S A. 2008;105(51):20446-20451.
• Negishi H, Fujita Y, Yanai H, Sakaguchi S, Shinohara M, Takayanagi H, Ohba Y, Taniguchi T, Honda K. Evidence for licensing of the IFN-g-induced IRF1 transcription factor by MyD88 in the TLR-dependent gene induction program. Proc Natl Acad Sci U S A. 2006 ;103(41):15136-15141
• Negishi H, Ohba Y, Yanai H, Takaoka A, Honma K, Yui K, Matsuyama T, Taniguchi T, Honda K. Negative regulation of Toll-like-receptor signaling by IRF-4. Proc Natl Acad Sci U S A. 2005 ;102(44):15989-15994.
• Sakaguchi S, Negishi H, Asagiri M, Nakajima C, Mizutani T, Takaoka A, Honda K, Taniguchi T. Essential role of IRF-3 in lipopolysaccharide-induced interferon-beta gene expression and endotoxin shock. Biochem Biophys Res Commun. 2003 ;306(4):860-6.

Current research

From three perspectives, I am trying to reveal and regulate the unknown mechanisms of immune responses.

 

1. Elucidation and application of new biological defense and antiviral response activation mechanism (research and development)

　During the infection, the pathogen component activates the innate immune responses, which leads to the activation of the adaptive immune response. In this primary response, humoral factors such as cytokines are produced. Among these cytokines, type I IFN especially plays a critical role for antiviral response. We have identified a compound that strongly incudes type I IFN from artificial compounds. Some compounds can be taken orally. From there, I am continuing to elucidate the mechanism of activation of new immune responses, as well as antiviral agents that can deal with a wide range of viruses including unknown viruses by activating immune responses, and as a new type of vaccine adjuvant. We are looking for a way to develop the compound of.病原体に感染すると、病原体成分によって自然免疫応答が活性化し、その後、適応免疫応答の活性化へと繋がります。この最初の応答の中でサイトカインと呼ばれる液性因子の産生が起こります。サイトカインの中でも特にI型IFNは抗ウイルス応答に重要です。我々は人工的な化合物の中から、このような応答を強く活性化する化合物を同定しました。中には経口摂取が可能な化合物も含まれます。そこから、新しい免疫応答の活性化メカニズムの解明を進めるとともに、免疫応答を活性化することで未知のウイルスを含めた広範なウイルスへ対処できる抗ウイルス剤、さらには新しいタイプのワクチンアジュバントとして、これらの化合物を発展させる道を模索しています。

 

2. Infectious disease drug discovery based on a new principle (drug development)新たな原理に基づいた感染症創薬(薬剤開発)

　We are advancing drug discovery research from two perspectives as infectious disease drug discovery. One is the inhibition of the entire transcriptional mechanism of pathogens. Many pathogens control gene expression with primitive and few molecules. We are advancing research and development of drugs that inhibit the entire transcription of pathogens by inhibiting the mechanism. The other is the inhibition of specific transcriptional mechanisms that control the immune response. Overreaction of the immune response leads to worsening of the condition. Also, depending on the type of infection or illness, there are types of immune responses that can be beneficial or detrimental to the body. Such an immune response is the opposite of pathogens, and gene transcription is complicatedly regulated by various molecules. Therefore, we are advancing research and development of drugs that inhibit only specific transcriptions and suppress only adverse responses.感染症創薬として2つの観点から創薬研究を進めています。1つは、病原体の転写機構全体の阻害です。多くの病原体は原始的、かつ、少ない分子によって、遺伝子の発現を制御しています。その機構を阻害することで、病原体の転写全体を阻害してしまう薬剤の開発研究を進めています。もう1つは、免疫応答を制御する特定の転写機構の阻害です。免疫応答の過応答は病態悪化に繋がります。また、感染症や病気の種類によって、生体に有益または不利益に働く免疫応答の種類があります。このような免疫応答は、病原体とは逆で、様々な分子によって複雑に遺伝子の転写が制御されています。そのため、特定の転写に限定して阻害し、不利益な応答だけを抑制する薬剤の研究開発を進めています。

 

3. Elucidation of the control mechanism of immune response (basic research)免疫応答の制御機構の解明(基礎研究)

　As basic research, we are promoting the identification of genes important for immune response and the elucidation of their mechanisms. Some mice are highly susceptible to influenza virus infection and cancer. Elucidation of such genes and mechanisms is expected to contribute to the establishment of control methods for immune responses and the development of vaccine adjuvants.我々は、基礎研究として免疫応答に重要な遺伝子の特定とその機構の解明を推進しています。その中には、インフルエンザウイルス感染、がんに対して強い感受性を示すマウスもいます。このような遺伝子や機構の解明は、免疫応答の制御法確立やワクチンアジュバントの開発に資すると期待しています。

 

　For us, “interest is justice” and the greatest cause. If you are interested, please feel free to contact us. It is also encouraging. The laboratory accommodates various people such as graduate students, undergraduate students, internship students, and corporate researchers.我々にとって「興味は正義」であり最大の大義名分です。 ご興味を持たれた方はお気軽にご連絡ください。励みにもなります。 研究室は大学院生、学部生、インターン生、企業の研究員など色々な方に対応しています。

Education

Research and career history

Selected publication

• Lee MSJ, Natsume-Kitatani Y, Temizoz B, Fujita Y, Konishi A, Matsuda K, Igari Y, Tsukui T, Kobiyama K, Kuroda E, Onishi M, Marichal T, Ise W, Inoue T, Kurosaki T, Mizuguchi K, Akira S, Ishii KJ, Coban C. B cell-intrinsic MyD88 signaling controls IFN-γ-mediated early IgG2c class switching in mice in response to a particulate adjuvant. Eur J Immunol., doi: 10.1002/eji.201848084 (2019).
• Temizoz B, Kuroda E, Ishii KJ. Combination and inducible adjuvants targeting nucleic acid sensors. Curr Opin Pharmacol.,doi: 10.1016/j.coph.2018.05.003 (2018).
• Kuroda E, Ozasa K, Temizoz B, Ohata K, Koo CX, Kanuma T, Kusakabe T, Kobari S, Horie M, Morimoto Y, Nakajima S, Kabashima K, Ziegler SF, Iwakura Y, Ise W, Kurosaki T, Nagatake T, Kunisawa J, Takemura N, Uematsu S, Hayashi M, Aoshi T, Kobiyama K, Coban C, Ishii KJ. Inhaled Fine Particles Induce Alveolar Macrophage Death and Interleukin-1α Release to Promote Inducible Bronchus-Associated Lymphoid Tissue Formation. Immunity,45(6), 1299-1310 (2016).
• Kitahata Y, Kanuma T, Hayashi M, Kobayashi N, Ozasa K, Kusakabe T, Temizoz B, Kuroda E, Yamaue H, Coban C, Yamamoto T, Kobiyama K, Aoshi T, Ishii KJ. Circulating nano-particulate TLR9 agonist scouts out tumor microenvironment to release immunogenic dead tumor cells. Oncotarget,7(31), 48860-48869 (2016).
• Temizoz B, Kuroda E, Ishii KJ. Vaccine adjuvants as potential cancer immunotherapeutics. Curr Opin Pharmacol.,doi: 10.1016/j.coph.2018.05.003 (2018).
• Kobiyama K, Temizoz B, Kanuma T, Ozasa K, Momota M, Yamamoto T, Aoshi T, Kuroda E, Ishii KJ. Species-dependent role of type I IFNs and IL-12 in the CTL response induced by humanized CpG complexed with β-glucan. Eur J Immunol.,46(5), 1142-51 (2016).
• Temizoz B, Kuroda E, Ohata K, Jounai N, Ozasa K, Kobiyama K, Aoshi T, Ishii KJ. TLR9 and STING agonists synergistically induce innate and adaptive type-II IFN. Eur J Immunol.,45(4), 1159-69 (2015).