A5039692874- Glycosylation and Glycoproteins Research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Galectins and Cancer Biology
- Carbohydrate Chemistry and Synthesis
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- RNA and protein synthesis mechanisms
- Cancer Mechanisms and Therapy
- Oral and gingival health research
- Biochemical and Molecular Research
- Proteoglycans and glycosaminoglycans research
- Enzyme Production and Characterization
- Molecular Biology Techniques and Applications
- Microbial Metabolites in Food Biotechnology
- Oral Health Pathology and Treatment
- Cancer Diagnosis and Treatment
- Viral Infections and Vectors
- Pediatric Hepatobiliary Diseases and Treatments
- Skin Diseases and Diabetes
- Mosquito-borne diseases and control
- NF-κB Signaling Pathways
- DNA Repair Mechanisms
- Ubiquitin and proteasome pathways
- Glioma Diagnosis and Treatment
Chulalongkorn University
2023-2025
Yale University
2021-2025
University of New Haven
2022-2025
Khon Kaen University
2012-2023
Faculty (United Kingdom)
2018
Resistance to DNA-damaging agents is a significant cause of treatment failure and poor outcomes in oncology. To identify unrecognized regulators cell survival we performed whole-genome CRISPR-Cas9 screen using with ionizing radiation as selective pressure, identified STING (stimulator interferon genes) an intrinsic regulator tumor survival. We show that regulates transcriptional program controls the generation reactive oxygen species (ROS), loss alters ROS homeostasis reduce DNA damage...
Abstract Increased glucose utilization is a feature of cancer cells to support cell survival, proliferation, and metastasis. An association between diabetes mellitus progression was previously demonstrated in cancers including cholangiocarcinoma (CCA). This study aimed determine the effects high on protein O-GlcNAcylation metastatic potentials CCA cells. Two pairs each parental low highly sublines were cultured normal (5.6 mM) or (25 media. The migration invasion abilities determined...
Membrane-bound oligosaccharides form the interfacial boundary between cell and its environment, mediating processes such as adhesion signaling. These structures can undergo dynamic changes in composition expression based on type, external stimuli, genetic factors. Glycosylation, therefore, is a promising target of therapeutic interventions for presently incurable forms advanced cancer. Here, we show that cholangiocarcinoma metastasis characterized by down-regulation Golgi α-mannosidase I...
Given that unnatural sugar expression is metabolically achieved, the kinetics and disposition of incorporation can lend insight into temporal localization preferences sialylation across cell surface. However, common detection schemes lack ability to detail molecular diversity distribution target moieties. Here we employed a mass spectrometric approach trace placement azido sialic acids on membrane glycoconjugates, which revealed substantial variations in efficiencies between N-/O-glycans,...
Abstract O-GlcNAcylation, an O-linked protein glycosylation with a single molecule of N-acetylglucosamine (GlcNAc), is reversibly controlled by O-GlcNAc transferase (OGT) and N-acetyl D-glucosaminidase (OGA). Aberrant O-GlcNAcylation contributes important role in initiation progression many human cancers. Elevation tumor tissues poor prognosis cholangiocarcinoma (CCA) patients have been reported. In this study, the promoting was further investigated CCA cell lines. Suppression using small...
Berberine is a natural compound found in several herbs. Anticancer activity of berberine was reported cancers, however, little known regarding the effects against cholangiocarcinoma (CCA). In this study, growth inhibitory on CCA cell lines and its molecular mechanisms were explored. Cell cycle distribution examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay flow cytometry. The expression levels regulatory proteins determined Western blot analysis....
A new method for detecting N-glycosylation reveals a role the TRAP complex and mechanism cell state–specific regulation.
O‐Glc NA cylation is a key post‐translational modification that modifies the functions of proteins. Associations between cylation, shorter survival cholangiocarcinoma ( CCA ) patients, and increased migration/invasion cell lines have been reported. However, specific cylated proteins OGP s) participate in promotion progression are poorly understood. s were isolated from human lines, KKU ‐213 ‐214, using click chemistry‐based enzymatic labeling system, identified LC ‐ MS / , searched against...
The leading cause of death in cancer patients is metastasis, for which an effective treatment still necessary. During cells aberrantly express several glycans that are correlated with poor patient outcome. This study was aimed toward exploring the effects O-GlcNAcylation on membranous N-glycans associated progression cholangiocarcinoma (CCA). Global CCA depleted using specific siRNA against O-GlcNAc transferase (OGT), transfers GlcNAc to acceptor proteins. Using HPLC-Chip/Time-of-Flight...
Abstract Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common cancer worldwide, local failure of disease following treatment with radiation therapy remains a major challenge for improving patient outcomes. We therefore designed CRISPR-Cas9 pooled genetic screen to identify signaling mechanisms that regulate HNSCC radiosensitivity. Using kinome gRNA library (763 genes 8 gRNAs each), Cal27 Detroit562 cells were screened using fractionated exposure ionizing as selection...
To gain insight into biological mechanisms that cause resistance to DNA damage, we performed parallel pooled genetic CRISPR-Cas9 screening for survival in high risk HNSCC subtypes. Surprisingly, and addition ATM, DNAPK, NFKB signaling, JAK1 was identified as a driver of tumor cell radiosensitivity. Knockout increases by enhancing the damage-induced G2 arrest, both knockout inhibition with abrocitinib prevent subsequent formation radiation-induced micronuclei. Loss function does not affect...
Abstract Aberrant glycosylation is recognized as a cancer hallmark that associated with development and progression. In this study, the clinical relevance significance of terminal fucose (TFG), by fucosyltransferase-1 (FUT1) in carcinogenesis progression cholangiocarcinoma (CCA) were demonstrated. TFG expression human hamster CCA tissues determined using Ulex europaeus agglutinin-I (UEA-I) histochemistry. Normal bile ducts rarely expressed while 47% had high was correlated shorter survival...
Oral lichen planus (OLP) is considered a chronic inflammatory immune-mediated disease of the oral mucosa. Immunopathogenesis OLP thought to be associated with cell-mediated immune dysregulation. O-GlcNAcylation form reversible glycosylation. It has been demonstrated that promoted nuclear factor kappa B (NF-κB) signalling. Activation NF-кB can induce expression nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which large intracellular...
Diabetes mellitus (DM) is an established risk for hepatocellular carcinoma (HCC), with unclarified mechanisms. This study investigated the effects of hyperglycemia on O-GlcNacylation in hepatocytes and its associations hepatocarcinogenesis.Mouse human HCC cell lines were used vitro model hyperglycemia. Western blotting was to determine high glucose cells. Twenty 4-week-old C3H/HeNJcl mice randomized into four groups: non-DM control, plus diethylnitrosamine (DEN), DM, DM DEN. induced using...
Abstract Secreted proteins are overexpressed in cholangiocarcinoma (CCA) and actively involved promoting metastatic spread. Many of these possess one or more sites glycosylation their various glycoforms have potential utility as prognostic diagnostic biomarkers. To evaluate the effects secretome on patient outcome, we elucidated patterns secreted by parental CCA cells using liquid chromatography‐mass spectrometry. Our analysis showed that was dominated fucosylated fucosialylated glycoforms....
Proteins destined for the secretory compartment of cell are cotranslationally translocated into endoplasmic reticulum. The majority these proteins N-glycosylated, a co- and posttranslational modification that ensures proper protein folding, stability, solubility, cellular localization. Here, we show [Formula: see text] subunit signal recognition particle receptor (SR) is required assembly N-glycosylation-competent translocon. We report guanine analog chemical probes identified by...
Protein asparagine (N)-glycosylation, which promotes folding and trafficking of cell surface receptors such as the EGFR, has not been considered a viable target in oncology due to essential non-redundant enzymatic activities required for glycan synthesis transfer. In mammals an exception this rule is presence oligosaccharyltransferase (OST) catalytic subunit paralogs, STT3A STT3B. Here we delineate chemical biology OST inhibitors develop approach limited inhibition N-glycosylation optimized...
The association between diabetes mellitus, hyperglycemia, and cholangiocarcinoma (CCA) development progression has been established. One speculation of the effects high glucose levels promoting CCA is via feeding substrate to aerobic glycolysis or so-called Warburg in cells. Several glycolytic enzymes transporters are upregulated further activated by conditions. However, increased uptake aggressive phenotypes under conditions might not be solely due this aberrant energy metabolism. High have...