A5031611833- Ginseng Biological Effects and Applications
- Genomics and Chromatin Dynamics
- Autophagy in Disease and Therapy
- Analytical Chemistry and Chromatography
- Epigenetics and DNA Methylation
- Pharmacological Effects of Natural Compounds
- Cellular transport and secretion
- Adipose Tissue and Metabolism
- Nuclear Structure and Function
- Protease and Inhibitor Mechanisms
- Advanced Proteomics Techniques and Applications
- RNA modifications and cancer
- MicroRNA in disease regulation
- Mass Spectrometry Techniques and Applications
- Ubiquitin and proteasome pathways
- Extracellular vesicles in disease
- Protein Degradation and Inhibitors
- Mitochondrial Function and Pathology
- Cardiac Imaging and Diagnostics
- Phytoestrogen effects and research
- Calcium signaling and nucleotide metabolism
- Retinoids in leukemia and cellular processes
- Signaling Pathways in Disease
- Erythrocyte Function and Pathophysiology
- Endoplasmic Reticulum Stress and Disease
Nanyang Technological University
2012-2023
Hutchinson-Gilford progeria (HGPS) is a premature ageing syndrome caused by mutation in LMNA, resulting truncated form of lamin A called progerin. Progerin triggers loss the heterochromatic marker H3K27me3, and senescence, which prevented telomerase. However, mechanism how progerin causes disease remains unclear. Here, we describe an inducible cellular system to model HGPS find that LAP2α (lamina-associated polypeptide-α) interacts with A, while its interaction significantly reduced....
Tumor hypoxia induces cancer cell angiogenesis, invasiveness, treatment resistance, and contributes to poor clinical outcome. However, the molecular mechanism by which tumor exerts a coordinated effect on different pathways enhance growth survival lead outcome is not fully understood. In this study, we attempt elucidate global protein expression functional changes in A431 epithelial carcinoma cells induced reoxygenation using iTRAQ quantitative proteomics biochemical assays. Quantitative...
(1) Background: Doxorubicin (DOX) is a frontline chemotherapeutic, but its side effects from oxidative stress leading to cardiotoxicity, pose significant challenges clinical use. We recently discovered novel family of proteolysis-resistant, cystine-dense, and cell-penetrating microproteins Panax ginseng that we term ginsentides. Ginsentides, such as the 31-residue TP1 coordinate multiple biological systems prevent vascular dysfunction endoplasmic reticulum induced by internal external...
The chromatin-associated proteome (chromatome) regulates cellular gene expression by restricting access of transcriptional machinery to template DNA, and dynamic re-modeling chromatin structure is required regulate critical cell functions including growth replication, DNA repair recombination, oncogenic transformation in progression cancer. Central the control these processes efficient regulation host cycle, which maintained rapid changes conformation during normal cycle progression. A...
In contrast to the intensely studied genetic and epigenetic changes that induce host cell transformation initiate tumor development, those promote malignant progression of cancer remain poorly defined. As emerging evidence suggests hypoxic microenvironment could re-model chromatin-associated proteome (chromatome) alter gene expression in cells, we hypothesized hypoxia-driven evolution chromatome promotes development therapy resistance cells. To test this hypothesis, isolated chromatins from...
Summary Erythropoiesis is marked by progressive changes in morphological, biochemical and mechanical properties of erythroid precursors to generate red blood cells ( RBC ). The earliest enucleated forms derived this process, known as reticulocytes, are multi‐lobular spherical. As reticulocytes mature, they undergo a series dynamic cytoskeletal re‐arrangements the expulsion residual organelles, resulting highly deformable biconcave s (normocytes). To understand significant, yet neglected...
Deamidation of asparaginyl residues in proteins produces a mixture asparaginyl, n-aspartyl, and isoaspartyl residues, which affects the proteins' structure, function, stability. Thus, it is important to identify quantify products evaluate effects biological systems. It still challenging task distinguish between n-Asp isoAsp deamidation proteome-wide analysis because their similar physicochemical properties. The quantification isomeric deamidated peptides also rather difficult coelution/poor...
Atherosclerosis arises from leukocyte infiltration and thickening of the artery walls constitutes a major component vascular disease pathology, but molecular events underpinning this process are not fully understood. Proteins containing an Asn-Gly-Arg (NGR) motif readily undergo deamidation asparagine to generate isoDGR structures that bind integrin αvβ3 on circulating leukocytes. Here we report identification motifs in human atherosclerotic plaque components including extracellular matrix...
The endosome-to-Golgi or endocytic retrograde trafficking pathway is an important post-Golgi recycling route. Here we show that amino acids (AAs) can stimulate the and regulate cell surface localization of certain Golgi membrane proteins. By testing components AA-stimulated mTORC1 signaling pathway, demonstrate SLC38A9, v-ATPase Ragulator, but not Rag GTPases mTORC1, are essential for trafficking. Arl5, ARF-like family small GTPase, interacts with Ragulator in AA-regulated manner both Arl5...
Sphingomyelinases are a family of enzymes that hydrolyze sphingomyelin to generate phosphocholine and ceramide. The brain distribution function neutral sphingomyelinase 2 (nSMase2) were elucidated in this study. nSMase2 mRNA expression was greatest the striatum, followed by prefrontal cortex, hippocampus, cerebellum, thalamus, brainstem, olfactory bulb. striatum had highest level protein expression, cerebellum. Dense immunolabeling observed including caudate-putamen, while moderately dense...
TGFBI-associated corneal dystrophies are inherited disorders caused by TGFBI gene variants that promote deposition of mutant protein (TGFBIp) as insoluble aggregates in the cornea. Depending on type and position amino acid substitution, may be amyloid fibrillar, amorphous globular or both, but molecular mechanisms drive these different patterns aggregation not fully understood. In current study, we report composition from lattice dystrophy patients Asian origin with H626R R124C mutation...
Hypoxia-induced vascular endothelial dysfunction (VED) is a significant contributor to several severe human diseases, including heart disease, stroke, dementia, and cancer. However, current treatment options for VED are limited due the lack of understanding underlying disease mechanisms therapeutic leads. We recently discovered heat-stable microprotein in ginseng, called ginsentide TP1, that has been shown reduce cardiovascular models. In this study, we use combination functional assays...
The lack of precise biomarkers that identify patients at risk for myocardial injury and stable angina delays administration optimal therapy. Hence, the search noninvasive could accurately stratify with impending heart attack, from coronary artery disease (CAD), is urgently needed in clinic. Herein, we performed comparative quantitative proteomics on whole plasma sampled (NMI), acute infarction (MI), healthy control subjects (Ctrl). We detected a total 371 proteins high confidence (FDR < 1%,...
Abstract Ginseng has been known as a “cure-all” traditional medicine to treat various illnesses and an adaptogen relieve stress. However, the active compounds of ginseng are small-molecule metabolites. Here we report ginsentides, which disulfide-dense, super-stable cell-penetrating peptides with 31–33 amino acids, adaptogens that restore homeostasis in response Using mass spectrometry-based target identification functional studies, show ginsentides promote vasorelaxation by producing nitric...
Studies have shown that the process of extracellular vesicles (EVs) secretion and lysosome status are linked. When is under stress, cells would secrete more EVs to maintain cellular homeostasis. However, governs lysosomal activity remains poorly defined we postulated certain proteins essential for biogenesis constantly synthesized preferentially sorted rather than lysosome. A pulsed stable isotope labelling amino acids in cell culture (pSILAC) based quantitative proteomics methodology was...
Stress and illness connection is complex involves multiple physiological systems. Panax ginsengs, reputed for their broad-spectrum "cure-all" effect, are widely prescribed to treat stress related illnesses. However, the identity of ginseng's medicinal compounds that relieve remains unresolved. Here, we identify ginsentides as principal bioactives coordinate systems restore homeostasis in response stress. Ginsentides disulfide-rich, cell-penetrating proteolytic-stable microproteins. Using...
Biological research often requires the use of sodium dodecyl sulfate (SDS) to solubilize protein samples; however, this detergent is not compatible with direct mass spectrometry (MS) analysis. Here, we report an online high-throughput proteomics method that permits standard in-solution digestion SDS-containing samples followed by liquid chromatography coupled tandem (LC–MS/MS) analysis using weak cation-exchange (WCX). This approach, called removal (Online reSDS), exploits properties WCX in...
Abstract Epidemiological data indicate that human cancer risk is significantly reduced by the consumption of soy‐based foods containing “phytoestrogen” genistein, which can signal via host cell estrogen receptors. While additional chemoprotective effects genistein induced epigenetic factors have also been reported, key molecules and mechanisms involved are poorly defined. We therefore investigated on chromatin‐bound proteins in receptor‐deficient line MDA‐MB‐231 insensitive to phytoestrogen...
Abstract Hypoxia-induced vascular endothelial dysfunction (VED) is a significant contributor to several severe human conditions, including heart disease, stroke, dementia, and cancer. However, current treatment options for VED are limited due lack of understanding the underlying disease mechanisms therapeutic leads. We recently discovered heat-stable microprotein in ginseng, known as ginsentide TP1 that has been shown reduce cardiovascular models. In this study, we use combination functional...
Insulin-resistant diabetes is a common metabolic disease with serious complications. Treatments directly addressing the underlying molecular mechanisms involving insulin resistance would be desirable. Our laboratory recently identified proteolytic-resistant cystine-dense microprotein from huáng qí (Astragalus membranaceus) called α-astratide aM1, which shares high sequence homology to leginsulins. Here we show that aM1 cell-penetrating mimetic, enters cells by endocytosis, and activates...