A5028857454- Acute Myocardial Infarction Research
- Cardiovascular Function and Risk Factors
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Adenosine and Purinergic Signaling
- Circular RNAs in diseases
- Heart Failure Treatment and Management
- Dermatologic Treatments and Research
- Systemic Sclerosis and Related Diseases
- Cancer-related molecular mechanisms research
- Cardiovascular Disease and Adiposity
- Cancer-related gene regulation
- Glycosylation and Glycoproteins Research
- MicroRNA in disease regulation
- Heme Oxygenase-1 and Carbon Monoxide
- Cardiac Ischemia and Reperfusion
- Neuroblastoma Research and Treatments
- Cancer Mechanisms and Therapy
- Neonatal Health and Biochemistry
- Epigenetics and DNA Methylation
- T-cell and B-cell Immunology
- Cardiac Imaging and Diagnostics
- Galectins and Cancer Biology
- Cancer, Hypoxia, and Metabolism
- Diabetic Foot Ulcer Assessment and Management
Duke-NUS Medical School
2021-2023
National University of Singapore
2023
The University of Texas Health Science Center at Houston
2018-2022
The University of Texas MD Anderson Cancer Center
2020-2021
ORCID
2021
Providence VA Medical Center
2020
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
2018
Gilead Sciences (United States)
2018
Brown University
2015
Human cancer cell lines are fundamental models for research and therapeutic strategy development. However, there is no characterization of circular RNAs (circRNAs) in a large number lines.Here, we apply four circRNA identification algorithms to heuristically characterize the expression landscape circRNAs across ~ 1000 human from CCLE polyA-enriched RNA-seq data. By using integrative analysis experimental approaches, explore landscape, biogenesis, functional consequences, drug response...
Epidemiologic evidence indicates that cigarette smoke (CS) is associated with the development of acute lung injury (ALI). We have previously shown brief CS exposure exacerbates lipopolysaccharide (LPS)-induced ALI in vivo and endothelial barrier dysfunction vitro. In this study, we found also exacerbated Pseudomonas-induced mice. demonstrated microvascular cells (ECs) isolated from mice exposed to had a greater permeability or incomplete recovery after challenges by LPS thrombin. Histone...
Idiopathic pulmonary fibrosis (IPF) is a chronic and deadly disease with poor prognosis few treatment options. Pathological remodeling of the extracellular matrix (ECM) by myofibroblasts key factor that drives pathogenesis, although underlying mechanisms remain unknown. Alternative polyadenylation (APA) has recently been shown to play major role in cellular responses stress driving expression fibrotic factors ECMs through altering microRNA sensitivity, but connection IPF not established....
Abstract Background Stress-induced hyperglycaemia at time of hospital admission has been linked to worse prognosis following acute myocardial infarction (AMI). In addition glucose, other glucose-related indices, such as HbA1c, glucose-HbA1c ratio (GHR), and stress-hyperglycaemia (SHR) are potential predictors clinical outcomes AMI. However, the optimal blood GHR, SHR cut-off values for predicting adverse post-AMI unknown. As such, we determined 1-year all cause mortality in diabetic...
Cigarette smoke (CS) exposure increases the risk for acute respiratory distress syndrome in humans and promotes alveolar-capillary barrier permeability lung injury animal models. However, underlying mechanisms are not well understood. Mitochondrial fusion fission essential mitochondrial homeostasis health disease. In this study, we hypothesized that CS caused endothelial via an imbalance of resultant oxidative stress dysfunction. We noted altered morphology by shortening networks causing...
Acute myocardial infarction (AMI) cases have decreased in part due to the advent of targeted therapies for standard modifiable cardiovascular disease risk factors (SMuRF). Recent studies reported that ST-elevation (STEMI) patients without SMuRF (termed "SMuRF-less") may be increasing prevalence and worse outcomes than "SMuRF-positive" patients. As these been limited STEMI comprised mainly Caucasian cohorts, we investigated changes mortality both SMuRF-less non-STEMI (NSTEMI) a multiethnic...
Abstract Smoking is one of the leading risk factors for cardiovascular diseases, including ischemic heart disease and hypertension. However, in acute myocardial infarction (AMI) patients, smoking has been associated with better clinical outcomes, a phenomenon termed “smoker’s paradox.” Given known detrimental effects on system, it proposed that beneficial effect outcomes due to age differences between smokers non-smokers therefore smoker’s pseudoparadox. The aim this study was evaluate...
Systemic sclerosis (SSc; scleroderma) is a multisystem fibrotic disease. The mammalian cleavage factor I 25-kD subunit (CFIm25; encoded by NUDT21) key regulator of alternative polyadenylation, and its depletion causes predominantly 3'UTR shortening through loss stimulation distal polyadenylation sites. A shortened will often lack microRNA target sites, resulting in increased mRNA translation due to evasion microRNA-mediated repression. Herein, we report that CFlm25 downregulated SSc skin,...
Despite the recognized significance of reversible protein lipidation (S-acylation) for T cell receptor signal transduction, enzymatic control this post-translational modification in cells remains poorly understood. Here, we demonstrate that DHHC21 (also known as ZDHHC21), a member DHHC family mammalian acyltransferases, mediates receptor-induced S-acylation proximal signaling proteins. Using Zdhhc21dep mice, which express functionally deficient version DHHC21, show is...
Systemic sclerosis (SSc; scleroderma) is a chronic disease that affects the skin and various internal organs. Dermal fibrosis major component of this disease. The mechanisms promote dermal remain elusive. Elevations in tissue adenosine levels subsequent engagement profibrotic A2B receptor (ADORA2B) have been shown to regulate multiple organs including lung, kidney, penis; however, role ADORA2B has not investigated. We undertook study test our hypothesis elevated expression drives development...
Key Points CD73-mediated adenosine production contributes to SCD pathogenesis by promoting erythrocyte 2,3-BPG and sickling. Specific inhibition of CD73 significantly attenuates disease severity mice provides a novel therapeutic strategy treat SCD.
Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by the pathological remodeling of air sacs as result excessive accumulation extracellular matrix (ECM) proteins, but mechanism governing robust protein expression poorly understood. Our recent findings demonstrate that alternative polyadenylation (APA) caused NUDT21 reduction important for increased fibrotic mediators and ECM proteins in lung fibroblasts shortening 3′-untranslated regions (3′-UTRs) mRNAs stabilizing their...
Idiopathic pulmonary fibrosis (IPF) is a fatal disease with limited treatment options. The role of the developmental transcription factor Sine oculis homeobox homolog 1 (SIX1) in pathophysiology lung not known. IPF tissue samples and IPF-derived alveolar type II cells (AT2) showed significant increase SIX1 mRNA protein levels, transcriptional coactivators EYA1 EYA2 were elevated. Six1 was also upregulated bleomycin-treated (BLM-treated) mice model spontaneous driven by deletion Telomeric...
Evolving evidence suggests that nicotine may contribute to impaired asthma control by stimulating expression of nerve growth factor (NGF), a neurotrophin associated with airway remodeling and hyperresponsiveness. We explored the hypothesis increases NGF reducing lung fibroblast (LF) microRNA-98 (miR-98) PPARγ levels, thus promoting remodeling. Levels NGF, miR-98, PPARγ, fibronectin 1 (FN1), endothelin-1 (EDN1, herein referred as ET-1), collagen (COL1A1 COL3A1) were measured in human LFs...
Adenosine is a potent signaling molecule that has paradoxical effects on lung diseases. We have previously demonstrated sustained adenosine exposure by inhibition of degradation impairs endothelial barrier integrity and causes intrinsic apoptosis through equilibrative nucleoside transporter 1/2 ‐mediated intracellular signaling. In this study, we further increased mitochondrial reactive oxygen species reduced respiration via , but not receptor‐mediated shown activates p38 c‐Jun N‐terminal...
Obesity is an important risk factor for acute myocardial infarction (AMI), but the interplay between metabolic health and obesity on AMI mortality has been controversial. In this study, we aimed to elucidate of short- long-term all-cause by in patients using data from a multi-ethnic national registry.A total 73,382 Singapore Myocardial Infarction Registry (SMIR) were included. These classified into four groups based presence or absence diseases, diabetes mellitus, hyperlipidaemia,...
Risk stratification plays a key role in identifying acute myocardial infarction (AMI) patients at higher risk of mortality. However, current AMI scores such as the Global Registry Acute Coronary Events (GRACE) score were derived from predominantly Caucasian populations and may not be applicable to Asian populations. We previously developed an national-level Singapore Myocardial Infarction (SMIR) confined ST-segment elevation (STEMI) did include non-STEMI (NSTEMI) patients. Here, we modified...
Abstract Despite the recognized significance of reversible protein lipidation (S-acylation) for T cell receptor signal transduction, enzymatic control this post-translational modification in cells remains poorly understood. Here, we demonstrate that DHHC21, a member DHHC family mammalian acyltransferases, mediates agonist-induced S-acylation proximal signaling proteins. Using Zdhhc21 dep mice expressing functionally deficient version show DHHC21 is calcium/calmodulin-dependent enzyme...
Cigarette smoke (CS) has been independently associated with the development of acute lung injury (ALI). We have previously demonstrated that CS exposure increases adenosine levels in mice and sustained to causes endothelial by equilibrative nucleoside transporter (ENT) 1/2-dependent mechanism. In this study we hypothesize CS-induced increased injury, leading susceptibility ALI, via ENT1/2- mediated mitochondrial dysfunction. Using inhaled Pseudomonas aeruginosa, a clinically relevant model...
Figure S1. Expression landscape of circRNAs across cancer cell lines. S2. Potential regulation EMT on biogenesis circRNAs. S3. Enrichment in clinically actionable genes. S4. Characterization functional effects and drug response circMYC cancer. S5. Therapeutic liability CTRP. S6. Examples modules CircRiC. Table Summary identified different (PDF 7931 kb)