A5079691801- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- Monoclonal and Polyclonal Antibodies Research
- Carbohydrate Chemistry and Synthesis
- Peptidase Inhibition and Analysis
- Cancer Research and Treatments
- Treatment of Major Depression
- Proteoglycans and glycosaminoglycans research
- Endometrial and Cervical Cancer Treatments
- Cancer Genomics and Diagnostics
- Caveolin-1 and cellular processes
- Renal Diseases and Glomerulopathies
- Nutrition and Health in Aging
- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- Mental Health Treatment and Access
- Cell Adhesion Molecules Research
- Immunotherapy and Immune Responses
- Pancreatic and Hepatic Oncology Research
- Insect and Pesticide Research
- Mental Health Research Topics
- Bee Products Chemical Analysis
- Bipolar Disorder and Treatment
- Phytochemistry Medicinal Plant Applications
- Influenza Virus Research Studies
Beth Israel Deaconess Medical Center
2019-2025
Harvard University
2019-2025
Kyorin University
2024-2025
Center for Drug Evaluation and Research
2023-2025
Hadassah Medical Center
2021-2024
United States Food and Drug Administration
2023
Osaka City University
2012-2021
Cleveland Clinic
2020
Nagoya University
1996-2016
Eiken Chemical (Japan)
1997-1998
Abstract The spike (S) glycoprotein in the envelope of SARS-CoV-2 is densely glycosylated but functions its glycosylation are unknown. Here we demonstrate that S recognized a glycan-dependent manner by multiple innate immune receptors including mannose receptor MR/CD206, DC-SIGN/CD209, L-SIGN/CD209L, and MGL/CLEC10A/CD301. Single-cell RNA sequencing analyses indicate such highly expressed cells tissues susceptible to infection. Binding above characterized affinities picomolar range...
Abstract Mucin-type O-glycans on glycoproteins are pivotal for biology and impact the quality of biotherapeutics. Furthermore, glycans host cells serve as ligands lectins/adhesins bacteria bacterium-host interactions in colonization or attachment/invasion bacteria. Defining structure-function relationship is hindered by a lack enzyme(s) to release sialylated from glycoproteins. Here we show identification endo-α-N-acetylgalactosaminidases (O-glycanases, GH101) with broad substrate...
The expression and implications of gangliosides in human osteosarcomas have not been systematically analyzed. In this study, we showed that GD3 GD2 are highly expressed the majority osteosarcoma cell lines derived from oral cavity regions. Introduction synthase cDNA into a GD3/GD2-negative (GD3/GD2-) subline resulted establishment GD3/GD2+ transfectant cells. They increased migration invasion activities wound healing Boyden chamber assays, respectively, compared to control When treated with...
Abstract Glycans within human lungs are recognized by many pathogens such as influenza A virus (IAV), yet little is known about their structures. Here we present the first analysis of N- and O- glycosphingolipid-glycans from total lungs, along with histological analyses IAV binding. The N-glycome lung contains extremely large complex-type N-glycans linear poly-N-acetyllactosamine (PL) [-3Galβ1–4GlcNAcβ1-] n extensions, which predominantly terminated in α2,3-linked sialic acid. By contrast,...
Alterations in protein glycosylation are observed many solid tumor types leading to formation of tumor-associated carbohydrate antigens (TACAs). The most common TACA is the Tn antigen (CD175), which a mucin-type O-GalNAc-Ser/Thr/Tyr glycan membrane and secreted glycoproteins. In addition, two other TACAs CA19-9 (sialyl-Lewis a), used as prognostic serum marker for pancreatic cancer, its isomer sialyl-Lewis x (SLex, CD15s), overexpressed cancer associated with metastasis. While CD175 may be...
Abstract Background Mood disorders, with a particular emphasis on depression, exert significant influence job performance and participation, leading to substantial levels of workforce presenteeism absenteeism. Often, individuals who rejoin the following depression-induced sick leave encounter lingering impairments are frequently prone repeated periods absence. Therefore, predicting occupational engagement in timely manner is crucial for devising appropriate management strategies affected by...
Gangliosides are expressed in neuroectoderm-derived tumors, and seemed to play roles the regulation of cancer properties. To examine behavior individual gangliosides, GM1/GD1b/GA1 synthase cDNA was introduced into melanoma cell line SK-MEL-37, changes tumor phenotypes were analyzed. The transfectant cells showed neo-expression GD1b, GT1b, GM1, reduced expression GM3, GM2, GD2, GD3. Function analyses revealed that had definite reduction growth invasion. Tyrosine-phosphorylation levels...
The Tn antigen is a neoantigen abnormally expressed in many human carcinomas and expression correlates with metastasis poor survival. To explore its biomarker potential, new antibodies are needed that specifically recognize this tumors. Here we generated two recombinant to the antigen, Remab6 as chimeric IgG1 antibody ReBaGs6 murine IgM characterized their specificities using multiple biochemical biological approaches. Both clustered structures, but most importantly do not glycoforms of IgA1...
Abstract The Madin-Darby canine kidney (MDCK) cell line is an in vitro model for influenza A virus (IAV) infection and propagation. MDCK-SIAT1 (SIAT1) humanized MDCK (hCK) lines are engineered cells that express N-glycans with elevated levels of sialic acid (Sia) α2,6-linkage (α2,6-Sia) recognized by many human IAVs. To characterize the N-glycan structures these potential changes compared to parental resulting from engineering, we analyzed at different passages, using both mass spectrometry...
The underlying pathology of immunoglobulin A (IgA) nephropathy (IgAN), the most common glomerulonephritis worldwide, is driven by deposition immune complexes containing galactose-deficient IgA1 [Tn(+)IgA1] in glomerular mesangium. Here, we report that novel anti-Tn circulating (anti-Tn CICs) contain predominantly IgM, representing large macromolecular ~1.2 megadaltons to several megadalton sizes together with Tn(+)IgA1 and some IgG. These are significantly elevated sera patients IgAN, which...
Differential recognition of glycan isomers by proteins is key to innate and adaptive immunity.
The Tn antigen (CD175) is an O-glycan expressed in various types of human adenocarcinomas, including colorectal cancer (CRC), though prior studies have relied heavily upon poorly characterized in-house generated antibodies and lectins. In this study, we explored expression CRC using ReBaGs6, a well-characterized recombinant murine antibody with high specificity for clustered antigen.Using well-defined monoclonal antibodies, patterns sialylated (STn) antigens were by immunostaining CRC,...
Mutations in genes encoding molecular chaperones can lead to chaperonopathies, but none have so far been identified causing congenital disorders of glycosylation. Here we two maternal half-brothers with a novel chaperonopathy, impaired protein O-glycosylation. The patients decreased activity T-synthase (C1GALT1), an enzyme that exclusively synthesizes the T-antigen, ubiquitous O-glycan core structure and precursor for all extended O-glycans. function is dependent on its specific chaperone...
Altered protein glycosylation is typically associated with cognitive defects and other phenotypes, but there a lack of knowledge about the brain glycoproteome. Here, we used newly available O-glycoprotease IMPa from Pseudomonas aeruginosa for comprehensive O-glycoproteomic analyses mouse brain. In this approach, total tryptic glycopeptides were prepared, extracted, purified, conjugated to solid support before an enzymatic cleavage by IMPa. O-glycopeptides analyzed...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT3-Vinylcoumarins and 3-vinylchromenes as dienes. Application to the synthesis of 3,4-fused coumarins chromenesToru Minami, Yasuyuki Matsumoto, Seigo Nakamura, Shinichiro Koyanagi, Masahiko YamaguchiCite this: J. Org. Chem. 1992, 57, 1, 167–173Publication Date (Print):January 1992Publication History Published online1 May 2002Published inissue 1 January...
Mucin-type O-linked glycosylation, a posttranslational modification affecting the stability and biophysical characteristics of proteins, requires C1GalT1 (T synthase) its obligate, X-linked chaperone Cosmc. Hypomorphic mutations cause renal failure via not yet established mechanisms. We hypothesize that impaired Cosmc-dependent O-glycosylation in podocytes is sufficient to disease. Podocyte-specific Cosmc knockout mice were generated phenotyped test this hypothesis. Female heterozygous...
The aberrant expression of the Tn antigen (CD175) on surface glycoproteins human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, chimeric anti-Tn-specific monoclonal IgG. However, antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation its N-glycans. Here describe generation an afucosylated Remab6 (Remab6-AF) in HEK293 cells which FX gene deleted (FXKO)....
Abstract There is an urgent need to develop new tumor biomarkers for early cancer detection, but the variability of tumor-derived antigens has been a limitation. Here we demonstrate novel anti-Tn antibody microarray platform detect Tn+ glycoproteins, near universal antigen in carcinoma-derived broad detection cancer. The uses specific recombinant IgG1 Tn (CD175) as capture reagent and IgM detecting reagent. These reagents were validated by immunohistochemistry recognizing using hundreds...
The methanol extract of Brazilian propolis was fractionated by HPLC, based on HuH13 (human hepatocellular carcinoma) cell cytotoxicity assay. Two isomers diterpenoid with a molecular formula C20H30O3 (MW: 318.46) were isolated. structures these colorless compounds determined as clerodane diterpenoids (I, 15-oxo-3, 13Z-kolavadien-17-oic acid; II, 15-oxo-3Z, 13E-kolavadien-17-oic acid).
Although regulatory mechanisms for immune cells with inhibitory signals via immunoreceptor tyrosine-based motifs are well known, transduced interaction between Siglecs and sialyl compounds on their counterreceptors into target have not been reported to date. In this study, we found that an astrocytoma cell line, AS, showed detachment from culture plates when co-cultured Siglec-9-expressing and/or soluble Siglec-9. Moreover, detached AS regrew as Siglec-9-deficient cells. They also increased...
ppGalNAc-T13 is upregulated along with reduced expression of GM1 in high metastatic sublines the murine Lewis lung cancer cell line, but little known about implication human cancers. Since lines showed levels ppGalNAc-T13, we analyzed surgical specimens to examine whether can be used as a prognostic marker or therapeutic target. We mRNA GALNT13 and its variant exon usages by real-time RT-PCR, results were evaluated correlating clinical data. Ninety-one analyzed. Consequently, recurrence-free...