A5038204612- Parasitic Infections and Diagnostics
- Gut microbiota and health
- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- Helicobacter pylori-related gastroenterology studies
- Protein Tyrosine Phosphatases
- Crystallization and Solubility Studies
- Endoplasmic Reticulum Stress and Disease
- X-ray Diffraction in Crystallography
- Inflammatory Bowel Disease
- interferon and immune responses
- Enterobacteriaceae and Cronobacter Research
- Epigenetics and DNA Methylation
- Amoebic Infections and Treatments
- Adipose Tissue and Metabolism
- ATP Synthase and ATPases Research
- Microscopic Colitis
- Mitochondrial Function and Pathology
- Infant Nutrition and Health
- Immunotherapy and Immune Responses
- Genetic factors in colorectal cancer
- Immune Response and Inflammation
- Liver Disease Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- Pancreatitis Pathology and Treatment
National University of Singapore
2014-2024
Mater Research
2008-2022
The University of Queensland
2007-2022
Translational Research Institute
2022
Singapore College of Traditional Chinese Medicine
2015-2021
Mater Health Services
2010-2013
Mucosa-associated bacteria are increased in inflammatory bowel disease (IBD), which suggests the possibility of an source digestible endogenous mucus substrate. We hypothesized that mucolytic IBD, providing substrate to sustain nonmucolytic mucosa-associated bacteria.Mucolytic were characterized by ability degrade human secretory mucin (MUC2) pure and mixed anaerobic cultures. Real-time PCR was used enumerate 46 IBD 20 control patients. Bacterial activity tested vitro using purified MUC2.We...
MUC2 mucin produced by intestinal goblet cells is the major component of mucus barrier. The inflammatory bowel disease ulcerative colitis characterized depleted and a reduced layer, but aetiology remains obscure. In this study we used random mutagenesis to produce two murine models disease, characterised basis nature inflammation in these mice, compared pathology with human colitis.By N-ethyl-N-nitrosourea identified distinct noncomplementing missense mutations Muc2 causing an colitis-like...
Cell surface mucin glycoproteins are highly expressed by all mucosal tissues, yet their physiological role is currently unknown. We hypothesized that cell mucins protect cells from infection. A rapid progressive increase in gastrointestinal expression of 1 (Muc1) followed infection mice with the bacterial pathogen Campylobacter jejuni. In first week following oral infection, C. jejuni was detected systemic organs vast majority Muc1–/– but never Muc1+/+ mice. Although entered epithelial both...
Blastocystis is a common gut eukaryote detected in humans and animals. It has been associated with gastrointestinal disease the past although recent metagenomic studies also suggest that it member of normal microbiota. This study investigates interactions between pathogenic human isolates belonging to subtype 7 (ST7) bacterial representatives Generally, ST7 exerts positive effect on viability representative bacteria except Bifidobacterium longum. Gene expression analysis flow cytometry...
The MUC13 transmembrane mucin is highly and constitutively expressed in the small large intestine. Although polymorphisms have been associated with human inflammatory bowel diseases susceptibility to Escherichia coli infection pigs, biological functions of are unknown. This study aimed explore whether modulates intestinal inflammation.Muc13(-/-) mice were generated, phenotyped challenged colitis-inducing agent, dextran sodium sulphate (DSS). Colitis was assessed by clinical symptoms...
Endoplasmic reticulum (ER) stress in intestinal secretory cells has been linked with colitis mice and inflammatory bowel disease (IBD). Endogenous glucocorticoids are important for homeostasis glucocorticoid drugs efficacious IBD. In Winnie ER caused by misfolding of the Muc2 mucin, dexamethasone (DEX) suppressed activation unfolded protein response (UPR), substantially restoring goblet cell production. lacking inflammation, a receptor antagonist increased stress, DEX induced N-glycosylation...
Blastocystis is a common gut protistan parasite in humans and animals worldwide, but its interrelationship with the host microbiota mucosal immune responses remains poorly understood. Different murine models of colonization were used to examine effect subtype (ST4) on microbial community adaptive system.Blastocystis ST4-colonized normal healthy mice Rag1-/- asymptomatically was able alter composition, mainly leading increases proportion Clostridia vadinBB60 group Lachnospiraceae NK4A136...
Rationale:The gut microbiota plays a significant role in the pathogenesis of inflammatory bowel disease (IBD).However, Blastocystis infection and Blastocystis-altered development diseases their underlying mechanisms are not well understood.Methods: We investigated effect ST4 ST7 on intestinal microbiota, metabolism, host immune responses, then explored microbiome dextran sulfate sodium (DSS)-induced colitis mice.Results: This study showed that prior colonization with conferred protection...
Abstract The large intestine harbors microorganisms playing unique roles in host physiology. beneficial or detrimental outcome of host‐microbiome coexistence depends largely on the balance between regulators and responder intestinal CD4 + T cells. We found that ulcerative colitis‐like changes after infection with protist Blastocystis ST7 a mouse model are associated reduction anti‐inflammatory Treg cells simultaneous expansion pro‐inflammatory Th17 responders. These alterations depended...
Abstract Blastocystis is a species complex that exhibits extensive genetic diversity, evidenced by its classification into several genetically distinct subtypes (ST). Although studies have shown the relationships between specific subtype and gut microbiota, there no study to show effect of ubiquitous ST1 on microbiota host health. Here, we colonization increased proportion beneficial bacteria Alloprevotella Akkermansia , induced Th2 Treg cell responses in normal healthy mice. ST1-colonized...
We recently characterized Winnie mice carrying a missense mutation in Muc2, leading to severe endoplasmic reticulum stress intestinal goblet cells and spontaneous colitis. In this study, we the immune responses due epithelial dysfunction. Winnie, there was fourfold increase activated dendritic (DCs; CD11c(+) major histocompatibility complex (MHC) class II(hi)) colonic lamina propria accompanied by decreased secretion of an inhibitor DC activation, thymic stromal lymphopoietin (TSLP). also...
Blastocystis is a common enteric protistan parasite that can cause acute, as well chronic, infection and associated with irritable bowel syndrome (IBS). However, the pathogenic status of remains unclear. In this study, we found antigens induced abundant expression proinflammatory cytokines, including interleukin 1β (IL-1β), IL-6, tumor necrosis factor alpha (TNF-α), in mouse intestinal explants, colitis colon, macrophages. Further investigation utilizing RAW264.7 murine macrophages showed...
Abstract Drug resistance is a major obstacle to the treatment of most human tumors. In this study, we find that dual-specificity phosphatase 16 (DUSP16) regulates chemotherapy in nasopharyngeal carcinoma, colorectal cancer, gastric and breast cancer. Cancer cells expressing higher DUSP16 are intrinsically more resistant chemotherapy-induced cell death than with lower expression. Overexpression cancer leads increased upon treatment. contrast, knockdown increases their sensitivity...
Dysfunction of adipocytes and adipose tissue is a primary defect in obesity obesity-associated metabolic diseases. Interferon regulatory factor 3 (IRF3) has been implicated adipogenesis. However, the role IRF3 disorders remains unclear. Here, we show that expression human tissues positively associated with insulin sensitivity negatively type 2 diabetes. In mouse pre-adipocytes, deficiency results increased PPARγ PPARγ-mediated adipogenic genes, leading to adipogenesis altered adipocyte...
Background & Aims: Dysbiosis is associated with gastric cancer (GC) development.However, no longitudinal study was carried out to identify key bacteria that could predict for GC progression.Here, we aimed investigate changes in bacterial metagenome prior and develop a microbiome-based predictive model accurately classify patients at risk of GC.Methods: Bacterial 16S rDNA sequenced from 89 antral biopsies obtained 43 participants.This nested prospective, study, whereby participants underwent...
Detection of cytosolic nucleic acids by pattern recognition receptors, including STING and RIG-I, leads to the activation multiple signalling pathways that culminate in production type I interferons (IFNs) which are vital for host survival during virus infection. In addition protective immune modulatory functions, IFNs also associated with autoimmune diseases. Hence, it is important elucidate mechanisms govern their expression. this study, we identified a critical regulatory function DUSP4...
<h3>Objective</h3> The anti-leukemic drugs, azathioprine and 6-mercaptopurine (6MP), are important in the treatment of inflammatory bowel disease but an alternative faster-acting, less-allergenic thiopurine, 6-thioguanine (6TG), can cause hepatic veno-occlusive disease/sinusoidal obstructive syndrome (SOS). Understanding SOS has been hindered by inability to ethically perform serial liver biopsies on patients lack animal model. <h3>Design</h3> Normal C57Bl/6 mice with specific genes altered...
The type I interferon system is essential for antiviral immune response and a primary target of viral evasion strategies. Here, we show that virus infection induces the expression MAPK phosphatase 5 (MKP5), dual-specificity (DUSP), in host cells. Mice deficient MKP5 were resistant to H1N1 influenza infection, which associated with increased IRF3 activation comparison WT mice. Increased responses also observed MKP5-deficient cells animals upon other RNA including vesicular stomatitis sendai...
The mitogen-activated protein kinase (MAPK) cascades are activated in innate immune cells such as macrophages upon the detection of microbial infection, critically regulating expression pro-inflammatory cytokines and chemokines TNF-α, IL-6 MCP-1. As a result, activation MAPKs is tightly regulated to ensure appropriate adequate responses. Dual-specificity phosphatases (DUSPs) family proteins which specifically dephosphorylates threonine tyrosine residues essential for MAPK negatively regulate...
Blastocystis spp. are widely prevalent extra cellular, non-motile anerobic protists that inhabit the gastrointestinal tract. Although have been associated with symptoms, irritable bowel syndrome and urticaria, their clinical significance has remained controversial. We established an ex vivo mouse explant model to characterize adhesion in context of tissue architecture presence mucin layer. Using confocal microscopy whole mounts two axenic isolates spp., subtype 7 notable differences...
// Heng Boon Low 1, 2 , Chin Wen Png Chunwei Li 3 De Yun Wang 4 Soon Justin Wong 2, 5 Yongliang Zhang 1 Department of Microbiology and Immunology, Yong Loo Lin School Medicine, National University Singapore, Singapore 117545, Immunology Programme, the Life Science Institute, 117597, Otorhinolaryngology, First Affiliated Hospital Sun Yat-Sen University, Guangzhou 510080, China Otolaryngology, Pathology, Hospital, 119074, Correspondence to: Zhang, email: miczy@nus.edu.sg Keywords:...
Nonalcoholic fatty liver disease is currently the most common and a leading cause of liver-related morbidity mortality. However, its pathogenesis remains largely unclear. We previously showed that mice deficient in mitogen-activated protein kinase (MAPK) phosphatase 5 (MKP5) spontaneously developed insulin resistance glucose intolerance, which are associated with visceral obesity adipose tissue inflammation. In this study, we discovered MKP5 more severe hepatic steatosis steatohepatitis age...
Notch1 plays various roles in cancer development, and Notch1-induced transactivation is controlled by phosphorylation of its cleaved intracellular domain. However, it unclear whether there are phosphatases capable dephosphorylating the transmembrane/intracellular region (NTM) to regulate function. Here, we show that DUSP6 can function as a phosphatase for Notch1, thereby regulating NTM stability transcriptional activity, thus influencing colorectal (CRC) development. In human CRC cells,...