慶應義塾研究者情報データベース

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• 2014年04月

  -

  2017年03月

  独立行政法人日本学術振興会, 特別研究員（DC1）

• 2017年04月

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  2026年05月

  小野薬品工業株式会社, 研究員

• 2022年06月

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  2024年06月

  Massachusetts Institute of Technology, 客員研究員

• 2026年06月

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  継続中

  慶應義塾大学, 理工学部 化学科, 専任講師（有期）

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• 2008年04月

  -

  2012年03月

  大阪大学, 理学部, 化学科

  大学, 卒業

• 2012年04月

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  2014年03月

  大阪大学, 理学研究科, 化学専攻

  大学院, 修了, 博士前期

• 2014年04月

  -

  2017年03月

  大阪大学, 理学研究科, 化学専攻

  大学院, 修了, 博士後期

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• 博士（理学）, 大阪大学, 課程, 2017年03月

免許・資格 【 表示 ／ 非表示 】

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• 危険物取扱者甲種, 2011年06月

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• ナノテク・材料 / 生物分子化学

• ナノテク・材料 / ケミカルバイオロジー

• ライフサイエンス / 生物有機化学

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• ケミカルバイオロジー、生物有機化学、天然物有機化学、糖質化学

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• Chemical Probe Discovery for DEAD-Box RNA-Binding Protein DDX21 Using Small-Molecule Microarrays

  Aiba, T., Calo, E. and Koehler, A. N.

  ACS Chem Biol 20 （ 8 ） 1928 - 1938 2025年08月

  ISSN  1554-8937

  　概要を見る

  The DEAD-box family of ATPases plays a critical role in nearly all stages of RNA metabolism, from transcription to degradation, and serves as a major regulator of biomolecular condensates. Dysregulation of DEAD-box proteins is well-established in a variety of diseases, including cancer and neurodegenerative disorders, making them attractive therapeutic targets. However, their classification as "undruggable" has historically hindered small-molecule-based modulation. In this study, we focus on DDX21, a member of the DEAD-box family involved in ribosome biogenesis and transcription regulation. As a proof of concept for targeting such RNA-binding proteins, we developed a lysate-based small-molecule microarray platform to identify compounds that directly bind DDX21. This screen led to the discovery of KI-DX-014, a small-molecule compound capable of inhibiting the interaction of DDX21 with RNA. KI-DX-014 modulated the RNA-dependent functions of DDX21, including its ATPase activity and biomolecular condensate formation. Furthermore, KI-DX-014 attenuated the DDX21-dependent release of P-TEFb from the 7SK snRNP complex in vitro, suppressed P-TEFb-dependent phosphorylation of the RNA polymerase II CTD, and induced developmental defects in zebrafish embryos. These findings reveal a previously unexploited therapeutic avenue and establish KI-DX-014 as a chemical probe for dissecting the biological functions of DDX21 in both normal physiology and disease states.

  • Access to Document (DOI)

• RNA-binding proteins and glycoRNAs form domains on the cell surface for cell-penetrating peptide entry

  Perr, J., Langen, A., Almahayni, K., Nestola, G., Chai, P., Lebedenko, C. G., Volk, R. F., Detres, D., Caldwell, R. M., Spiekermann, M., Hemberger, H., Bisaria, N., Aiba, T., Sanchez-Rivera, F. J., Tzelepis, K., Calo, E., Mockl, L., Zaro, B. W. and Flynn, R. A.

  Cell 188 （ 7 ） 1878 - 1895 e25 2025年04月

  ISSN  1097-4172

  　概要を見る

  The composition and organization of the cell surface determine how cells interact with their environment. Traditionally, glycosylated transmembrane proteins were thought to be the major constituents of the external surface of the plasma membrane. Here, we provide evidence that a group of RNA-binding proteins (RBPs) is present on the surface of living cells. These cell-surface RBPs (csRBPs) precisely organize into well-defined nanoclusters enriched for multiple RBPs and glycoRNAs, and their clustering can be disrupted by extracellular RNase addition. These glycoRNA-csRBP clusters further serve as sites of cell-surface interaction for the cell-penetrating peptide trans-activator of transcription (TAT). Removal of RNA from the cell surface, or loss of RNA-binding activity by TAT, causes defects in TAT cell internalization. Together, we provide evidence of an expanded view of the cell surface by positioning glycoRNA-csRBP clusters as a regulator of communication between cells and the extracellular environment.

  • Access to Document (DOI)

• Synthesis and Application of Immunomodulatory Natural Products

  Fujimoto Y., Shiokawa Z., Inuki S., Aiba T., Arai Y.

  Yuki Gosei Kagaku Kyokaishi Journal of Synthetic Organic Chemistry 81 （ 9 ） 867 - 876 2023年

  ISSN  00379980

  　概要を見る

  In recent years, as the immunomodulatory mechanisms have been greatly elucidated, examples of selective immunomodulatory actions have been found for a wide variety of small-molecule compounds, including natural products. In particular, with regard to immune activation through inhibition of immunosuppressive molecules, which has been the focus of recent attention, research on inhibitors of enzymatic immunosuppressive molecules has focused on small molecules. On the other hand, it is important to understand the molecules derived from microorganisms that activate or suppress the immune system, for understanding the mechanisms of infection or the protection against the microbes. This group of molecules is also a treasure trove of diverse immunomodulatory structures. In this article, we introduce the development of synthetic methods for immunomodulatory molecules based on natural compounds and their related compounds. Firstly, the development of IDO1 inhibitors, which are attracting attention as targets for anti-tumor agents by inhibiting immunosuppressive molecules, based on longamide B, a natural product derived from marine sponges, was introduced. In the latter half, the synthesis and development of the selective immune modulatory compounds, based on microbial innate immune receptor ligands. are introduced. The compounds include 1,7-bisphosphate heptose (HBP) as a novel factor involved in innate immune activation via TIFA, and also inositol phospholipids (EhPIb from Entamoeba histolytica and Ac1PIM1 from Mycobacterium tuberculosis) involved in regulating immune mechanisms were described with the characteristic methods of phosphate introduction.

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• Polar functional group-containing glycolipid CD1d ligands modulate cytokine-biasing responses and prevent experimental colitis

  Inuki, S., Hirata, N., Kashiwabara, E., Kishi, J., Aiba, T., Teratani, T., Nakamura, W., Kojima, Y., Maruyama, T., Kanai, T. and Fujimoto, Y.

  Sci Rep 10 （ 1 ） 15766 2020年09月

  ISSN  2045-2322

  　概要を見る

  The MHC class I-like molecule CD1d is a nonpolymorphic antigen-presenting glycoprotein, and its ligands include glycolipids, such as alpha-GalCer. The complexes between CD1d and ligands activate natural killer T cells by T cell receptor recognition, leading to the secretion of various cytokines (IFN-gamma, IL-4, IL-17A, etc.). Herein, we report structure-activity relationship studies of alpha-GalCer derivatives containing various functional groups in their lipid acyl chains. Several derivatives have been identified as potent CD1d ligands displaying higher cytokine induction levels and/or unique cytokine polarization. The studies also indicated that flexibility of the lipid moiety can affect the binding affinity, the total cytokine production level and/or cytokine biasing. Based on our immunological evaluation and investigation of physicochemical properties, we chose bisamide- and Bz amide-containing derivatives 2 and 3, and evaluated their in vivo efficacy in a DSS-induced model of ulcerative colitis. The derivative 3 that exhibits Th2- and Th17-biasing responses, demonstrated significant protective effects against intestinal inflammation in the DSS-induced model, after a single intraperitoneal injection.

  • Access to Document (DOI)

• Convergent Synthesis of Digalactosyl Diacylglycerols

  Inuki, S., Kishi, J., Kashiwabara, E., Aiba, T. and Fujimoto, Y.

  Org Lett 19 （ 24 ） 6482 - 6485 2017年12月

  ISSN  1523-7052

  　概要を見る

  Efficient convergent chemical syntheses of digalactosyl diacylglycerols (DGDGs), which have both a galactose-galactose alpha(1-->6)-linkage and a galactose-glycerol beta-linkage along with a diacylglycerol containing various kinds of fatty acids, have been accomplished. In order to achieve a concise synthesis, we chose to use allylic protective groups as permanent protective groups. We have also achieved alpha- and beta-selective glycosylations for the respective linkages with high yields as the key steps.

  • Access to Document (DOI)

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