A5053099774- Glycosylation and Glycoproteins Research
- Immunotherapy and Immune Responses
- Carbohydrate Chemistry and Synthesis
- Galectins and Cancer Biology
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- Ubiquitin and proteasome pathways
- Click Chemistry and Applications
- Parasitic infections in humans and animals
- Parasitic Infections and Diagnostics
- Advanced Electron Microscopy Techniques and Applications
- Peptidase Inhibition and Analysis
- Signaling Pathways in Disease
- Phagocytosis and Immune Regulation
- Cell death mechanisms and regulation
- Fungal Biology and Applications
- Proteoglycans and glycosaminoglycans research
- interferon and immune responses
- Polysaccharides and Plant Cell Walls
- Bacteriophages and microbial interactions
- Bone health and treatments
- Phytoplasmas and Hemiptera pathogens
- Photoreceptor and optogenetics research
Academia Sinica
2010-2025
Genomics Research Center, Academia Sinica
2016-2025
Center for Genomic Science
2023
Research Center for Applied Science, Academia Sinica
2020
Institute of Physics, Academia Sinica
2020
Japan Synchrotron Radiation Research Institute
2020
Institute of Chemistry, Academia Sinica
2020
SPring-8
2020
Hokkaido University
2020
Genomics (United Kingdom)
2013
Protein glycosylation is an important posttranslational process, which regulates protein folding and functional expression. Studies have shown that abnormal in tumor cells affects cancer progression malignancy. In the current study, we identified sialylated proteins using alkynyl sugar probe two different lung cell lines, CL1-0 CL1-5 with distinct invasiveness derived from same parental line. Among proteins, epidermal growth factor receptor (EGFR) was chosen to understand effect of...
Glycomics is emerging as a new field for the biology of complex glycoproteins and glycoconjugates. The lack versatile glycan-labeling methods has presented major obstacle to visualizing at cellular level studying To address this issue, we developed fluorescent labeling technique based on Cu(I)-catalyzed [3 + 2] cycloaddition, or click chemistry, which allows rapid, versatile, specific covalent glycans bearing azide groups. method entails generating probe from nonfluorescent precursor,...
Developing tools for investigating the cellular activity of glycans will help to delineate molecular basis aberrant glycosylation in pathological processes such as cancer. Metabolic oligosaccharide engineering, which inserts sugar-reporting groups into glycoconjugates, represents a powerful method imaging localization, trafficking, and dynamics isolating them glyco-proteomic analysis. Herein, we show that alkyne-reporting group can be incorporated glycans. The alkyne is small, inert,...
It is widely accepted that the heavily glycosylated glycoprotein gp120 on surface of HIV-1 shields peptide epitopes from recognition by immune system and may promote infection in vivo interaction with dendritic cells transport to tissue rich CD4(+) T such as lymph nodes. A conserved cluster oligomannose glycans has been identified epitope recognized broadly HIV-1-neutralizing monoclonal antibody 2G12. Oligomannose are also ligands for DC-SIGN, a C-type lectin found cells. Multivalency...
The up-regulation of fucosyltransferase 8 (FUT8), the only enzyme catalyzing α1,6-fucosylation in mammals, has been observed several malignant cancers including liver, ovarian, thyroid, and colorectal cancers. However, pathological role regulatory mechanism FUT8 remain largely unknown. In current study, we report that expression is up-regulated nonsmall cell lung cancer (NSCLC) correlates with tumor metastasis, disease recurrence, poor survival patients NSCLC. Knocking down aggressive lines...
LIGHT is a new member of tumor necrosis factor (TNF) cytokine family derived from an activated T cell cDNA library. mRNA highly expressed in splenocytes, PBL, CD8(+) infiltrating lymphocytes, granulocytes, and monocytes but not the thymus cells examined. Introduction into MDA-MB-231 human breast carcinoma caused complete suppression vivo. Histological examination showed marked neutrophil infiltration expressing parental or Neo-transfected tumors. Interferon gamma (IFNgamma) dramatically...
The folding energetics of the mono-N-glycosylated adhesion domain human immune cell receptor cluster differentiation 2 (hCD2ad) were studied systematically to understand influence N-glycan on energy landscape. Fully elaborated structures accelerate by 4-fold and stabilize beta-sandwich structure 3.1 kcal/mol, relative nonglycosylated protein. N-glycan's first saccharide unit accounts for entire acceleration 2/3 native state stabilization. remaining third stabilization is derived from next...
Globo H (GH) is a hexasaccharide specifically overexpressed on variety of cancer cells and therefore, good candidate for vaccine development. To identify the optimal carrier adjuvant combination, we chemically synthesized linked GH to protein, including keyhole limpet hemocyanion, diphtheria toxoid cross-reactive material (CRM) 197 (DT), tetanus toxoid, BSA, combined with an adjuvant, it was administered mice study immune response. Glycan microarray analysis antiserum obtained indicated that...
C-type lectins (CTLs) are proteins that contain one or more carbohydrate-recognition domains (CRDs) require calcium for sugar binding and share high degree of sequence homology tertiary structure. CTLs whose CRD EPN (Glu-Pro-Asn) tripeptide motifs have potential to bind mannose (Man), N-acetylglucosamine (GlcNAc), glucose (Glc) l-fucose (Fuc), whereas those with QPD (Glu-Pro-Asp) galactose (Gal) N-acetylgalactosamine (GalNAc). We report here the first time a direct comparison monosaccharide...
Significance Oral squamous cell carcinoma (OSCC) is characterized by high morbidity and mortality, few therapeutic options. Here, we show that the expression of B7 Homolog 3 (B7-H3) significantly up-regulated in tumor tissue OSCC patients correlated with increased size poor survival rate. Comparing N-glycans B7-H3 from Ca9-22 oral cancer cells Smulow–Glickman (SG) normal cells, also found glycans contain terminal α-galactose are more diverse higher fucosylation better interaction immune...
Significance This report reveals the influence of sialylation on activation epidermal growth factor receptor (EGFR) and sensitivity to tyrosine kinase inhibitors (TKIs) against EGFR phosphorylation. By utilizing biochemical approaches, we demonstrated that suppresses phosphorylation by inhibiting EGF binding dimerization. In TKI-resistant lung cancer cell line with L858R/T790M mutations EGFR, levels at Y1068, Y1086, Y1173 are upregulated, can partially suppress these sites enhance TKI. These...
Significance Glioblastoma multiforme (GBM) is a deadly brain tumor. More than 50% of patients who suffer from GBM die within 15 mo even received all possible medical treatment. In this study we report that the glycolipid stage-specific embryonic antigen-4 (SSEA-4) highly expressed on surface both cells and specimens. We further demonstrate growth tumor inhibited when anti–SSEA-4 antibody administered to experimental mice, suggesting research proof concept for treatment other SSEA-4 + cancers.
Significance Glioblastoma multiforme (GBM) is the most malignant brain tumor. The recurrence or chemoresistance of GBM attributed to presence cancer stem cells (CSCs). Although many studies indicate that CD133 protein a biomarker for CSC (GSC) enrichment, not specific GSCs and also present on cells. In this study, we report ganglioside D3 (GD3) only an alternative marker but additional identification enrichment GSCs. We further prove properties CSCs in are suppressed when GD3 synthase...
The globo-series glycosphingolipids (GSLs) are unique glycolipids exclusively expressed on the cell surface of various types cancer and have been used as targets for development vaccines therapeutics. A practical enzymatic method has developed synthesis glycans, where conversion Gb4 to Gb5 (SSEA-3) glycan based microbial galactosyltransferase LgtD is relatively inefficient compared other steps. To improve efficiency, we explored two human (β3GalT5) isozymes in cells this reaction found that...
CLEC4F, a member of C-type lectin, was first purified from rat liver extract with high binding affinity to fucose, galactose (Gal), N-acetylgalactosamine (GalNAc), and un-sialylated glucosphingolipids GalNAc or Gal terminus. However, the biological functions CLEC4F have not been elucidated. To address this question, we examined expression distribution murine determined its specificity by glycan array, investigated function using knockout (Clec4f−/−) mice. We found that is heavily...
Carbohydrate-based vaccines have shown therapeutic efficacy for infectious disease and cancer. The mushroom Ganoderma lucidum (Reishi) containing complex polysaccharides has been used as antitumor supplement, but the mechanism of immune response rarely studied. Here, we show that mice immunized with a l -fucose (Fuc)-enriched Reishi polysaccharide fraction (designated FMS) induce antibodies against murine Lewis lung carcinoma cells, increased antibody-mediated cytotoxicity reduced production...
Significance Glycosylation is considered to be a major posttranslational modification, and O -GlcNAcylation known affect protein folding function. In this study, we show that the methyltransferase EZH2, which catalyzes methylation of histone 3 at lysine 27 form H3K27m3, requires enhance its stability enzymatic activity promote tumor progression. We further in N-terminal region EZH2 stabilizes enzyme S729 catalytic domain essential for di- trimethylation. This study indicates selective...
Significance Cancer stem cells are cancer with self-renewal and tumor-growth properties important targets for development of anticancer therapy. We have found breast can be enriched by stage-specific embryonic antigen 3 (SSEA-3) known protein markers (CD24 CD44), as few 10 such develop tumor in mice. Also, the enzyme galactosyltransferase (β3GalT5) biosynthesis SSEA-3 is expressed but not normal cells, both β3GalT5 shown to essential cell survival. These findings led a new strategy proof...
The globo-series glycosphingolipids (GSLs) SSEA3, SSEA4, and Globo-H specifically expressed on cancer cells are found to correlate with tumor progression metastasis, but the functional roles of these GSLs key enzyme β1,3-galactosyltransferase V (β3GalT5) that converts Gb4 SSEA3 remain largely unclear. Here we show expression β3GalT5 significantly correlates poor survival in patients, breast form a complex membrane lipid raft caveolin-1 (CAV1) focal adhesion kinase (FAK) which then interact...
Non–small cell lung cancer (NSCLC), a major life-threatening disease accounting for 85% of all cases, has been treated with tyrosine kinase inhibitors (TKIs), but often resulted in drug resistance, and approximately 60% TKI-resistant cases are due to acquired secondary (epithelial growth factor receptor) EGFR-T790M mutation. To identify alternative targets NSCLC mutation, we found that the three globo-series glycosphingolipids increasingly expressed on this type lines, among them, increase...
Decoy receptor 3 (DcR3), a soluble belonging to the TNFR superfamily, is for both Fas ligand (FasL) and LIGHT. It has been demonstrated that DcR3 up-regulated in lung colon cancers, thus promoting tumor growth by neutralizing cytotoxic effects of FasL In this study, we found DcR3.Fc profoundly modulated dendritic cell differentiation maturation from CD14(+) monocytes, including up-regulation CD86/B7.2, down-regulation CD40, CD54/ICAM-1, CD80/B7.1, CD1a, HLA-DR. Moreover, DcR3-treated cells...
Decoy receptor 3 (DcR3) is a soluble of the tumor necrosis factor superfamily and readily detected in certain cancer patients. Recently, we demonstrated that DcR3.Fc-treated dendritic cells skew T cell responses to helper type 2 phenotype. In this study, further asked its ability modulate CD14+ monocyte differentiation into macrophages induced by macrophage-colony stimulating vitro. We found DcR3.Fc was able expression several macrophage markers, including CD14, CD16, CD64, human leukocyte...
Protein glycosylation is an important post-translational modification of proteins that has profound effects on structure and function. However, the complex non-templated nature glycans been a barrier to studying many their basic features, especially proteome-wide scale. Here, we introduce glycoproteomic method, glycoprotein identification glycan mapping (GIDmap), tailors isolation specific subpopulations based display metabolically inserted alkynyl sugar probes can be selectively manipulated...
Galectin (Gal) family members are a type of soluble lectin, and they play important roles in immunomodulation. Their redundant have been proposed. We previously found that Gal-1 promotes the formation Ab-secreting plasma cells, but B cells from Gal-1-deficient control animals produce comparable amounts Abs. In current study, we used synthetic sulfomodified N-acetyllactosamine (LacNAc) analogs short hairpin RNAs for Gal-8 to demonstrate redundancy effects on cell formation. were both...