A5072123911- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Axon Guidance and Neuronal Signaling
- Angiogenesis and VEGF in Cancer
- Chemical Synthesis and Analysis
- Cancer-related gene regulation
- Click Chemistry and Applications
- Genomics and Phylogenetic Studies
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Bacterial Genetics and Biotechnology
- Ubiquitin and proteasome pathways
- CRISPR and Genetic Engineering
- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Transgenic Plants and Applications
- Neuroendocrine regulation and behavior
- Lipid metabolism and biosynthesis
- Ion Channels and Receptors
- Viral Infections and Immunology Research
- Histone Deacetylase Inhibitors Research
- Cellular transport and secretion
- Hippo pathway signaling and YAP/TAZ
- Photosynthetic Processes and Mechanisms
- ATP Synthase and ATPases Research
Osaka University of Pharmaceutical Sciences
2017-2024
Osaka University
2002-2023
Beth Israel Deaconess Medical Center
2014
Harvard University
2014
Center for Vascular Biology Research
2014
Massachusetts Institute of Technology
2014
Material Sciences (United States)
2014
Tokyo Metropolitan Institute of Medical Science
2014
Systems Biology Institute
2008-2012
The University of Tokyo
2005-2012
There is an urgent need to develop novel drugs reduce the mortality from severe infectious diseases with emergence of new pathogens, including Coronavirus disease 2019 (COVID-19). Although current effectively suppress proliferation immune cell activation, and inflammatory cytokine functions, they cannot completely infections sepsis. In this study, we focused on endothelial cell-specific protein, Roundabout 4 (Robo4), which suppresses vascular permeability by stabilizing cells, investigated...
The genetic encoding of synthetic or "non-natural" amino acids promises to diversify the functions and structures proteins. We applied rapid codon-reassignment for creating Escherichia coli strains unable terminate translation at UAG "stop" triplet, but efficiently decoding it as various tyrosine lysine derivatives. This complete change in meaning enabled protein synthesis with these non-natural molecules multiple defined sites, addition 20 canonical acids. was also redefined E. BL21 strain,...
Interleukin-5 (IL-5), a major hematopoietin, stimulates eosinophil proliferation, migration, and activation, which have been implicated in the pathogenesis of allergic inflammatory diseases, such as asthma. The specific IL-5 receptor (IL-5R) consists α subunit (IL-5RA) common β (βc). binding to IL-5R on target cells induces rapid tyrosine phosphorylation activation various cellular proteins, including JAK1/JAK2 STAT1/STAT5. Here, we report crystal structure dimeric complex with IL-5RA...
The undifferentiated state of muscle stem (satellite) cells (MuSCs) is maintained by the canonical Notch pathway. Although three bHLH transcriptional factors, Hey1, HeyL and Hes1, are considered to be potential effectors pathway exerting anti-myogenic effects, neither nor Hes1 inhibits myogenic differentiation cell lines. Furthermore, whether these factors work redundantly or cooperatively unknown. Here, we showed cell-autonomous functions Hey1 in MuSCs using conditional genetic null mice....
Abstract The calcitonin receptor‐like receptor (CRLR), a class B GPCR, forms heterodimer with activity‐modifying protein 2 (RAMP2), and serves as the adrenomedullin (AM) to control neovascularization, while CRLR RAMP1 form gene‐related peptide (CGRP) receptor. Here, we report crystal structures of RAMP2 extracellular domain alone in complex domain. CRLR–RAMP2 exhibits several intermolecular interactions that were not observed previously reported CRLR–RAMP1 complex, thus shape putative...
The benzophenone photophore is widely used to photo-cross-link macromolecules. Recent developments in genetic code expansion have allowed the biosynthesis of proteins with p-benzoyl-L-phenylalanine (pBpa) at defined sites, for covalent bonding interacting proteins. However, structure a photo-cross-linked protein complex had not been revealed, and thus neither actual "photobridge" nor influence this bridge on overall was known. In study, we determine crystal cross-linked liver oncoprotein...
A derivative of Nε-benzyloxycarbonyl-L-lysine with a photo-reactive diazirinyl group, Nε-[((4-(3-(trifluoromethyl)-3H-diazirin-3-yl)benzyl)oxy)carbonyl]-L-lysine, was site-specifically incorporated into target proteins in mammalian cells. The photo-crosslinker is able to react not only residues as distant about 15 Å but also those closer proximity, thus enabling "wide-range" photo-crosslinking proteins.
We previously reassigned the amber UAG stop triplet as a sense codon in Escherichia coli by expressing UAG-decoding tRNA and knocking out prfA gene, encoding release factor 1. triplets were left at ends of about 300 genes genome. In present study, we showed that detrimental effect reassignment could be alleviated increasing efficiency translation instead reducing number UAGs isolated an suppressor tRNA(Gln) variant displaying enhanced suppression activity, introduced it into knockout strain,...
Posttranslational modifications (PTMs) of proteins play a crucial role in regulating protein-protein interactions, enzyme activity, subcellular localization, and stability the protein. SET domain, bifurcated 1 (SETDB1) is histone methyltransferase that regulates methylation H3 on lysine 9 (H3K9), gene silencing, transcriptional repression. The C-terminal region SETDB1 key site for PTMs, essential its activity mammalian insect cells. In this study, we aimed to evaluate more precisely effect...
Naringenin (NRG) is a plant-derived flavonoid. Due to its antioxidant, anti-inflammatory, and analgesic activities it beneficial human health often used as functional food ingredient; however, has poor water solubility low in vivo bioavailability. Therefore, the efficacy of NRG can be improved by enhancing increase gastrointestinal absorption. Conventional methods for formulation are very complex use toxic organic solvents, making them impractical production foods. The objective this study...
Although transcription factors regulating endothelial cell (EC)-specific gene expression have been identified, it is not known how those induce EC-specificity. We previously reported that DNA hypomethylation of the proximal promoter elicits EC-specific Roundabout4 (Robo4). However, mechanisms establishing Robo4 remain unknown. In this study, we demonstrated hypermethylated demethylated as human iPS cells differentiate into cells. Reporter assays ETV2, an ETS family factor, bound to motifs in...
Roundabout guidance receptor 4 (Robo4) is an endothelial cell-specific that stabilizes the vasculature in pathological angiogenesis. Although Robo4 has been shown to suppress vascular hyperpermeability induced by growth factor (VEGF) angiogenesis, role of inflammation poorly understood. In this study, we investigated during inflammation. Endotoxemia models using Robo4-/- mice showed increased mortality and leakage. cells, suppressed tumor necrosis α (TNFα)-induced stabilizing VE-cadherin at...
Abstract Accumulating evidence suggests that endothelial cells can be useful therapeutic targets. One of the potential targets is an cell-specific protein, Roundabout4 (ROBO4). ROBO4 has been shown to ameliorate multiple diseases in mice, including infectious and sepsis. However, its mechanisms are not fully understood. In this study, using RNA-seq analysis, we found downregulates prostaglandin-endoperoxide synthase 2 (PTGS2), which encodes cyclooxygenase-2. Mechanistic analysis reveals...
The molecular basis of endothelial cell (EC)-specific gene expression is poorly understood. Roundabout 4 (Robo4) expressed exclusively in ECs. We previously reported that the 3-kb 5'-flanking region human Robo4 contains information for lineage-specific Our studies implicated a critical role GA-binding protein and specificity 1 (SP1) mediating overall levels. However, these transcription factors are also non-ECs. In this study, we tested hypothesis epigenetic mechanisms contribute to...
Abstract The site-specific incorporation of cross-linkable designer amino acids into proteins is useful for covalently bonding protein complexes upon exposure to light. This technology can be used study networks protein-protein interactions in living cells; however, date it has only been applicable use with a narrow range cell types, due the limited availability plasmid-based transfection protocols. In present study, we achieved adenovirus-based expression variant an archaeal pyrrolysyl-tRNA...