A5006426839- Advanced Proteomics Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Physiological and biochemical adaptations
- Mass Spectrometry Techniques and Applications
- Ubiquitin and proteasome pathways
- Aquaculture Nutrition and Growth
- Neurobiology and Insect Physiology Research
- Autophagy in Disease and Therapy
- Plant Stress Responses and Tolerance
- Aquaculture disease management and microbiota
- Histone Deacetylase Inhibitors Research
- Malaria Research and Control
- Glycosylation and Glycoproteins Research
- Epigenetics and DNA Methylation
- Endoplasmic Reticulum Stress and Disease
- Invertebrate Immune Response Mechanisms
- Photosynthetic Processes and Mechanisms
- Computational Drug Discovery Methods
- Cellular transport and secretion
- Virus-based gene therapy research
- Insect symbiosis and bacterial influences
- Oral microbiology and periodontitis research
- Mitochondrial Function and Pathology
- Trypanosoma species research and implications
- Cancer, Hypoxia, and Metabolism
National University of Singapore
2016-2025
Institute of Hematology & Blood Diseases Hospital
2022
Chinese Academy of Medical Sciences & Peking Union Medical College
2022
Agency for Science, Technology and Research
2007-2021
Bioinformatics Institute
2021
Guangdong Academy of Agricultural Sciences
2015
Institute of Plant Protection
2015
Qingdao Agricultural University
2012
Fujian Normal University
2010
University of Madras
2010
The mechanism of action artemisinin and its derivatives, the most potent anti-malarial drugs, is not completely understood. Here we present an unbiased chemical proteomics analysis to directly explore this in Plasmodium falciparum. We use alkyne-tagged analogue coupled with biotin identify 124 covalent binding protein targets, many which are involved essential biological processes parasite. Such a broad targeting spectrum disrupts biochemical landscape parasite causes death. Furthermore,...
Autophagy is a catabolic process in response to starvation or other stress conditions sustain cellular homeostasis. At present, histone deacetylase inhibitors (HDACIs) are known induce autophagy cells through inhibition of mechanistic target rapamycin (MTOR) pathway. FOXO1, an important transcription factor regulated by AKT, also play role induction. the FOXO1 HDACIs-induced has not been reported. In this study, we first observed that HDACIs increased expression at mRNA and protein level....
Abstract Salt exclusion at the roots and salt secretion in leaves were examined a mangrove, A vicennia officinalis . The non‐secretor mangrove B ruguiera cylindrica was used for comparative study of hydrophobic barrier formation roots. Bypass flow reduced when seedlings previously treated with high concentration. biseriate exodermis detected salt‐treated roots, along an enhanced deposition barriers endodermis. These Na + loading into xylem, accounting 90–95% Prominent found even absence...
Abstract Metastasis is a significant health issue. The standard mode of care combination chemotherapy and targeted therapeutics but the 5-year survival rate remains low. New/better drug targets that can improve outcomes patients with metastatic disease are needed. complex process, each step conferred by set genetic aberrations. Mapping molecular changes associated metastasis improves our understanding etiology this contributes to pipeline therapeutics. Here, phosphoproteomics...
TFEB (transcription factor EB) is a master regulator of lysosomal biogenesis, function and autophagy. The transcriptional activity mainly controlled by its phosphorylation status mediated the MTOR (mechanistic target rapamycin [serine/threonine kinase]) complex 1 (MTORC1). At present, little known whether other forms posttranslational modifications (PTMs) such as acetylation also affects activity. In this study, we first observed that well-established histone deacetylase inhibitor...
Abstract Understanding the mechanism of action (MOA) bioactive natural products will guide endeavor to improve their cellular activities. Artemisinin and its derivatives inhibit cancer cell proliferation, yet with much lower efficiencies than roles in killing malaria parasites. To efficacies on cells, we studied MOA artemisinin using chemical proteomics found that free heme could directly activate artemisinin. We then designed synthesized a derivative, ART‐TPP, which is capable targeting...
Drug target identification is a critical step toward understanding the mechanism of action drug, which can help one improve drug's current therapeutic regime and expand potential. However, in vitro affinity-chromatography-based vivo activity-based protein profiling approaches generally face difficulties discriminating specific drug targets from nonspecific ones. Here we describe novel approach combining isobaric tags for relative absolute quantitation with clickable to specifically...
The antimalarial artemisinin (ART) possesses anticancer activity, but its underlying mechanism remains largely unclear. Using a chemical proteomics approach with artemisinin-based activity probes, we identified over 300 specific ART targets. This reveals an whereby promiscuously targets multiple critical biological pathways and leads to cancer cell death. cytotoxicity of against colorectal (CRC) cells rather than normal colon epithelial is due the elevated capacity heme synthesis in cells....
Abstract Pyrazinamide is a sterilizing first-line tuberculosis drug. Genetic, metabolomic and biophysical analyses previously demonstrated that pyrazinoic acid, the bioactive form of prodrug pyrazinamide (PZA), interrupts biosynthesis coenzyme A in Mycobacterium by binding to aspartate decarboxylase PanD. While most drugs act inhibiting protein function upon target binding, we find here acid only weak enzyme inhibitor. We show PanD triggers degradation caseinolytic protease ClpC1-ClpP. Thus,...
To date, the exact targets and mechanism of action curcumin, a natural product with anti-inflammatory anti-cancer properties, remain elusive. Here we synthesized cell permeable curcumin probe (Cur-P) an alkyne moiety, which can be tagged biotin for affinity enrichment, or fluorescent dye visualization direct-binding protein in situ. iTRAQ(TM) quantitative proteomics approach was applied to distinguish specific binding from non-specific ones. In total, 197 proteins were confidently identified...
Colorectal cancer is the second leading killer worldwide and presently most common among males in Singapore. The study aimed to detect changes of protein profiles associated with process colorectal tumorigenesis identify specific markers for early detection diagnosis or as potential therapeutic targets. Seven pairs tissues adjacent normal mucosa were examined by two-dimensional gel electrophoresis at basic pH range (pH 7–10). Intensity 34 spots detected statistical significance. 16...
White spot syndrome virus (WSSV) is at present one of the major pathogens in shrimp culture worldwide. The complete genome this has been sequenced recently. To identify structural and functional proteins WSSV, purified virions were separated by SDS-PAGE. Twenty-four protein bands excised, in-gel digested with trypsin, subjected to matrix-assisted laser desorption ionization-time flight mass spectrometry electrospray ionization tandem spectrometry, respectively. Eighteen matching open reading...
To identify novel tyrosine kinase substrates that have never been implicated in cancer, we studied the phosphoproteomic changes MCF10AT model of breast cancer progression using a combination phosphotyrosyl affinity enrichment, iTRAQ™ technology, and LC-MS/MS. Using complementary MALDI- ESI-based mass spectrometry, 57 unique proteins comprising kinases, phosphatases, other signaling were detected to undergo differential phosphorylation during disease progression. Seven these (SPAG9,...
Abstract The specialized salt glands on the epidermis of halophytic plants secrete excess salts from tissues by a mechanism that is poorly understood. We examined as putative and water bi‐regulatory units can respond swiftly to altering environmental cues. tropical mangrove tree species ( A vicennia officinalis ) able grow under fluctuating salinities (0.7–50.0 dS m −1 at intertidal zones, its offer an excellent platform investigate their dynamic responses rapidly changing salinities....
Salinity affects growth and development of plants, but mangroves exhibit exceptional salt tolerance. With direct exposure to salinity, mangrove roots possess specific adaptations tolerate stress. Therefore, studying the early effects on can help us better understand tolerance mechanisms. Using two-month-old greenhouse-grown seedlings tree Avicennia officinalis subjected NaCl treatment, we profiled gene expression changes in by RNA-sequencing. Of 6547 genes that were differentially regulated...
Target-identification and understanding of mechanism-of-action (MOA) are challenging for development small-molecule probes their application in biology drug discovery. For example, although aspirin has been widely used more than 100 years, its molecular targets have not fully characterized. To cope with this challenge, we developed a novel technique called quantitative acid-cleavable activity-based protein profiling (QA-ABPP) combination the following two parts: (i) (ABPP) iTRAQ™ proteomics...
Abstract Omic approaches have been increasingly used in the zebrafish model for holistic understanding of molecular events and mechanisms tissue functions. However, plasma is rarely omic profiling because technical challenges collecting sufficient blood. In this study, we employed two mass spectrometric (MS) a comprehensive characterization proteome, i.e. conventional shotgun liquid chromatography-tandem spectrometry (LC-MS/MS) an overview study quantitative SWATH (Sequential Window...
Yeasts contain bioactive components that can enhance fish immune robustness and disease resistance. Our study focused on analyzing intestinal immunoregulatory pathways in zebrafish (Danio rerio) using iTRAQ 2D LC-MS/MS to quantify proteins. Zebrafish were fed either control diet (C) or supplemented with autolyzed Cyberlindnera jadinii (ACJ). KEGG analysis revealed ACJ yeast induced increased abundance of proteins related arginine proline metabolism, phagosome, C-lectin receptor signaling,...
In the present study, profiles of protein expression were examined during early development zebrafish, an increasingly popular experimental model in vertebrate and human diseases. By 2-DE, initial increase spots from 6 h post-fertilization (hpf) to 8-10 hpf was observed. There no dramatic change up 18 hpf, but significant changes occurred subsequent stages. Interestingly, 49% proteins detected at remained detectable by 1 week age. To map patterns 2-D gels, MALDI-TOF/TOF MS employed identify...
Cerberus rynchops (dog-faced water snake) belongs to Homalopsidae of Colubroidea (rear-fanged snakes). So far, venom compositions snakes the family are not known. To determine composition C. rynchops, we have used both transcriptomics and proteomics approaches. The gland transcriptome revealed 104 ESTs presence three known snake protein families, namely, metalloprotease, CRISP, C-type lectin. In addition, identified two proteins that showed sequence homology ficolin, a mammalian with...