A5008413888- Cardiac electrophysiology and arrhythmias
- Cytokine Signaling Pathways and Interactions
- IL-33, ST2, and ILC Pathways
- Liver Disease Diagnosis and Treatment
- Cardiac Fibrosis and Remodeling
- Heart Rate Variability and Autonomic Control
- Cardiovascular Function and Risk Factors
- Viral Infections and Immunology Research
- Liver physiology and pathology
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- ECG Monitoring and Analysis
- RNA Research and Splicing
- Cardiomyopathy and Myosin Studies
- Endoplasmic Reticulum Stress and Disease
- Drug-Induced Hepatotoxicity and Protection
- Connective tissue disorders research
- Immune Cell Function and Interaction
- Atrial Fibrillation Management and Outcomes
- Cardiac Arrhythmias and Treatments
- Ocular Diseases and Behçet’s Syndrome
- Lipid metabolism and disorders
- Eosinophilic Disorders and Syndromes
- Occupational and environmental lung diseases
- Liver Diseases and Immunity
- Cancer Genomics and Diagnostics
National Heart Centre Singapore
2017-2025
National University of Singapore
2014-2025
Max Delbrück Center
2024
The University of Adelaide
2012-2021
Royal Adelaide Hospital
2012-2021
The University of Melbourne
2012-2021
South Australian Health and Medical Research Institute
2015-2021
Victorian Comprehensive Cancer Centre
2021
Tan Tock Seng Hospital
2019
Our Lady of Fatima University
2019
Interleukin-11 is important for lung fibroblast activation in idiopathic pulmonary fibrosis, and its signaling represents a therapeutic target.
We studied the role of interleukin 11 (IL11) signaling in pathogenesis nonalcoholic steatohepatitis (NASH) using hepatic stellate cells (HSCs), hepatocytes, and mouse models NASH.We stimulated human fibroblasts, HSCs, or hepatocytes with IL11 other cytokines analyzed them by imaging, immunoblot, functional assays enzyme-linked immunosorbent assays. Mice were given injections IL11. disruption receptor subunit alpha1 gene (Il11ra1-/-) mice Il11ra1+/+ fed a high-fat methionine-...
For healthspan and lifespan, ERK, AMPK mTORC1 represent critical pathways inflammation is a centrally important hallmark
The pivot is critical to rotors postulated maintain atrial fibrillation (AF). We reasoned that wavefronts circling the should broaden amplitude distribution of bipolar electrograms because directional information encoded in these signals. aimed determine whether Shannon entropy (ShEn), a measure signal distribution, could differentiate from surrounding peripheral regions and thereby assist clinical rotor mapping.Bipolar electrogram recordings were studied 4 systems: (1) computer simulations...
Abstract IL11 is important for fibrosis in non-alcoholic steatohepatitis (NASH) but its role beyond the stroma liver disease unclear. Here, we investigate of hepatocyte lipotoxicity. Hepatocytes highly express IL11RA and secrete response to lipid loading. Autocrine activity causes death through NOX4-derived ROS, activation ERK, JNK caspase-3, impaired mitochondrial function reduced fatty acid oxidation. Paracrine stimulates hepatic stellate cells fibrosis. In mouse models NASH,...
Inhibition of IL11 signaling limits drug-induced liver damage and promotes hepatic regeneration in a mouse model.
Interleukin 11 (IL11) is upregulated in inflammatory conditions, where it mostly believed to have anti-inflammatory activity. However, recent studies suggest instead that IL11 promotes inflammation by activating fibroblasts. Here, we assessed whether pro- or Primary cultures of human kidney, lung skin fibroblasts were stimulated with resulted the transient phosphorylation signal transducer and activator transcription 3 (STAT3) sustained activation extracellular signal-regulated protein...
The kidney has large regenerative capacity, but this is compromised when damage excessive and renal tubular epithelial cells (TECs) undergo SNAI1-driven growth arrest. Here we investigate the role of IL11 in TECs, injury repair. stimulation TECs induces ERK- p90RSK-mediated GSK3β inactivation, SNAI1 upregulation pro-inflammatory gene expression. Mice with acute upregulate leading to expression dysfunction, which not seen Il11 deleted mice or administered a neutralizing antibody either...
Interleukin 11 (IL11) is a profibrotic cytokine, secreted by myofibroblasts and damaged epithelial cells. Smooth muscle cells (SMCs) also secrete IL11 under pathological conditions express the receptor. Here we examined effects of SMC-specific, conditional expression murine in transgenic mouse (Il11SMC). Within days transgene activation, Il11SMC mice developed loose stools progressive bleeding rectal prolapse, which was associated with 65% mortality two weeks. The bowel inflamed, fibrotic...
Transforming growth factor beta-1 (TGFβ1) is a major driver of vascular smooth muscle cell (VSMC) phenotypic switching, an important pathobiology in arterial disease. We performed RNA-sequencing TGFβ1-stimulated human aortic or VSMCs which revealed large and consistent upregulation Interleukin 11 (IL11). IL11 has unknown function VSMCs, highly express the receptor alpha, suggestive autocrine loop. In vitro, activated ERK signaling, but inhibited STAT3 activity, caused VSMC switching to...
Background: Marfan syndrome (MFS) is associated with TGF (transforming growth factor) β–stimulated ERK (extracellular signal-regulated kinase) activity in vascular smooth muscle cells (VSMCs), which adopt a mixed synthetic/contractile phenotype. In VSMCs, TGFβ induces IL (interleukin) 11) that stimulates ERK-dependent secretion of collagens and MMPs (matrix metalloproteinases). Here, we examined the role IL11 MFS aorta. Methods: We used echocardiography, histology, immunostaining,...
IL11 initiates fibroblast activation but also causes epithelial cell dysfunction. The mechanisms underlying these processes are not known. We report that IL11-stimulated ERK/P90RSK activity the phosphorylation of LKB1 at S325 and S428, leading to its inactivation. This inhibits AMPK activates mTOR across types. In stromal cells, ERK LKB1/AMPK which is associated with activation, ⍺SMA expression, myofibroblast transformation. hepatocytes IL11/ERK SNAI1 Across IL11-induced phenotypes were...
Abstract Peutz‐Jeghers syndrome (PJS) is associated with early‐onset gastrointestinal polyposis caused by hereditary inactivating pathogenic variants in the tumor suppressor gene STK11 ( LKB1 ). Due to lack of prophylactic therapies, management PJS polyps requires frequent surveillance. Interestingly, studies mouse models have revealed that stromal cells drive polyp formation, but detailed understanding cell types and interactions involved has been lacking. Using single‐cell RNA sequencing...
Cardiac fibrosis is a common pathological process in heart disease, representing therapeutic target. Transforming growth factor β (TGFβ) the canonical driver of cardiac and was recently shown to be dependent on interleukin 11 (IL11) for its profibrotic effects fibroblasts. In opposite direction, recombinant human IL11 has been reported as anti-fibrotic anti-inflammatory mouse heart. this study, we determined expression cardiomyocytes pathobiology function. We used Cre-loxP system generate...
Interleukin-11 (IL11) is important for fibrosis and inflammation, but its role in the pancreas unclear. In pancreatitis, fibrosis, inflammation organ dysfunction are associated with pancreatic stellate cell (PSC)-to-myofibroblast transformation. Here, we show that IL11 stimulation of PSCs, which specifically express IL11RA pancreas, results transient STAT3 phosphorylation, sustained ERK activation PSC activation. contrast, IL6 PSCs caused phosphorylation did not result or Pancreatitis...
The artemisinin compounds, which are well-known for their potent therapeutic antimalarial activity, possess in vivo and vitro antitumor effects. Although the anticancer effect of compounds has been extensively reported, precise mechanisms underlying its cytotoxicity remain under intensive study. In present study, a high-throughput quantitative proteomics approach was applied to identify differentially expressed proteins HCT116 colorectal cancer cell line with artesunate (ART) treatment....
Background: Marfan Syndrome (MFS) is an inherited connective tissue disorder caused by mutations in the FBN1 (fibrillin-1) gene. Lung abnormalities are common MFS, but their pathogenesis poorly understood. IL11 (interleukin-11) causes aortic disease a mouse model of MFS and was studied here lung. Methods: We examined histological molecular phenotypes lungs Fbn1 C1041G/+ mice (mouse [mMFS]), established MFS. To identify IL11-expressing cells, we used immunohistochemistry on 4- 16-week-old :...
Abstract Interleukin‐11 (IL11) is important for fibroblast‐to‐myofibroblast transformations. Here, we examined the signalling and phenotypic effects of inhibiting IL11 using neutralizing antibodies against or its cognate receptor (IL11RA) in a mouse model acute severe pressure overload. C57BL/6J mice underwent ascending aortic constriction (AAC) surgery were randomized to anti‐IL11, anti‐IL11RA, isotype control (20 mg/kg, bi‐weekly 2 weeks). AAC induced expression IL11, IL11RA extracellular...
Abstract Background: Cardiac fibrosis is a common pathological process in heart disease and represents therapeutic target. TGFβ the canonical driver of cardiac was recently shown to be dependent on IL11 for its profibrotic effects fibroblasts. In opposite direction, recombinant human has been reported as anti-fibrotic also anti- inflammatory mouse heart. Objectives: this study, we determined expression cardiomyocytes pathobiology function. Methods: We used Cre-loxP system generate...