A5058260498- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- RNA Research and Splicing
- 3D Printing in Biomedical Research
- Cardiovascular Function and Risk Factors
- Cardiac Fibrosis and Remodeling
- Congenital heart defects research
- Genetics and Neurodevelopmental Disorders
- Cancer-related gene regulation
- Signaling Pathways in Disease
- Chromatin Remodeling and Cancer
- Peptidase Inhibition and Analysis
- Cancer Mechanisms and Therapy
- Pancreatic function and diabetes
- Cardiac Structural Anomalies and Repair
- Liver physiology and pathology
- MicroRNA in disease regulation
- RNA and protein synthesis mechanisms
- Cancer-related molecular mechanisms research
- Mitochondrial Function and Pathology
- Congenital Heart Disease Studies
- Genomic variations and chromosomal abnormalities
- Chemotherapy-induced cardiotoxicity and mitigation
- Atherosclerosis and Cardiovascular Diseases
Université de Montréal
2022-2025
National University Health System
2016-2024
Genome Institute of Singapore
2016-2024
Montreal Heart Institute
2022-2024
University Health System
2021-2024
Agency for Science, Technology and Research
2022-2023
National University of Singapore
2010-2023
Cardiovascular Institute Hospital
2021-2022
National University Heart Centre Singapore
2020-2022
National University Hospital
2022
Circular RNA (circRNA) is a newly validated class of single-stranded RNA, ubiquitously expressed in mammalian tissues and possessing key functions including acting as microRNA sponges transcriptional regulators by binding to RNA-binding proteins. While independent studies confirm the expression circRNA various tissue types, genome-wide heart has yet be described detail.We performed deep RNA-sequencing on ribosomal-depleted isolated from 12 human hearts, 25 mouse hearts across 28-day...
DNA methylation acts as a mechanism of gene transcription regulation. It has recently gained attention possible therapeutic target in cardiac hypertrophy and heart failure. However, its exact role cardiomyocytes remains controversial. Thus, we knocked out the main de novo methyltransferase cardiomyocytes, DNMT3A, human induced pluripotent stem cells. Functional consequences methylation-deficiency under control stress conditions were then assessed engineered tissue from knockout cell-derived...
Identifying genetic markers for heterogeneous complex diseases such as heart failure is challenging and requires prohibitively large cohort sizes in genome-wide association studies to meet the stringent threshold of statistical significance. On other hand, chromatin quantitative trait loci, elucidated by direct epigenetic profiling specific human tissues, may contribute toward prioritizing subthreshold variants disease association.
Objective Gastric cancer (GC) comprises multiple molecular subtypes. Recent studies have highlighted mesenchymal-subtype GC (Mes-GC) as a clinically aggressive subtype with few treatment options. Combining studies, we derived and applied consensus Mes-GC classifier to define the enhancer landscape revealing disease vulnerabilities. Design Transcriptomic profiles of ~1000 primary GCs cell lines were analysed derive classifier. Clinical genomic associations performed across >1200 patients...
Objective Gastric cancer (GC) is a leading cause of mortality, with ARID1A being the second most frequently mutated driver gene in GC. We sought to decipher -specific GC regulatory networks and examine therapeutic vulnerabilities arising from loss. Design Genomic profiling patients including Singapore cohort (>200 patients) was performed derive mutational signatures inactivation across molecular subtypes. Single-cell transcriptomic profiles -mutated GCs were analysed tumour...
There have been considerable efforts to engineer three-dimensional (3D) microfluidic environments enhance cellular function over conventional two-dimensional (2D) cultures in chips, but few involve topographical features, such as micro/nano-grooves, which are beneficial for cell types of cardiac, skeletal and neuronal lineages. Here we developed a cost-effective scalable method incorporate micro-topographical cues into chips induce alignment. Using commercially available optical media molds...
Abstract Conventional two‐dimensional (2D) monolayer cultures of HepaRG cells allow in vitro maintenance many liver‐specific functions. However, cellular dedifferentiation and functional deterioration over an extended culture period the conventional 2D have hampered its applications drug testing. To address this issue, we developed tethered spheroids on Arg–Gly–Asp (RGD) galactose‐conjugated substratum with optimized hybrid ratio as three‐dimensional (3D) human hepatocyte model. The gene...
The human genome folds in 3 dimensions to form thousands of chromatin loops inside the nucleus, encasing genes and cis-regulatory elements for accurate gene expression control. Physical tethers are anchored by DNA-binding protein CTCF cohesin ring complex. Because heart failure is characterized hallmark changes, it was recently reported that substantial CTCF-related reorganization underpins myocardial stress-gene response, paralleled domain boundary changes observed knockout.We undertook an...
Transcriptional reactivation of telomerase catalytic subunit (TERT) is a frequent hallmark cancer, occurring in 90% human malignancies. However, specific mechanisms driving TERT remain obscure for many tumor types and particular gastric cancer (GC), leading cause global mortality. Here, through comprehensive genomic epigenomic analysis primary GCs GC cell lines, we identified the transcription factor early B 1 (EBF1) as transcriptional repressor inactivation EBF1 function major upregulation....
Abstract Background Enhancers are distal cis -regulatory elements required for cell-specific gene expression and cell fate determination. In cancer, enhancer variation has been proposed as a major cause of inter-patient heterogeneity—however, most predicted regions remain to be functionally tested. Methods We analyzed 132 epigenomic histone modification profiles 18 primary gastric cancer (GC) samples, normal tissues, 28 GC lines using Nano-ChIP-seq technology. applied Capture-based...
Primary valvular heart disease is a prevalent cause of morbidity and mortality in both industrialized developing countries. Although the primary consequence myocardial dysfunction, treatment diseases centers around valve repair or replacement rather than prevention reversal dysfunction. This particularly evident mitral regurgitation (MR), which invariably results eccentric hypertrophy left ventricular (LV) failure absence timely replacement. The mechanism LV dysfunction severe MR entirely...
Lifestyle and environmental-related exposures are important risk factors for hepatocellular carcinoma (HCC), suggesting that epigenetic dysregulation significantly underpins HCC. We profiled 30 surgically resected tumours the matched adjacent normal tissues to understand aberrant events associated with HCC.We identified tumour differential enhancers genes by analysing H3K27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) Hi-C/HiChIP data from samples of patients...
Although genome wide association studies (GWAS) in large populations have identified hundreds of variants associated with common diseases such as coronary artery disease (CAD), most disease-associated lie within non-coding regions the genome, rendering it difficult to determine downstream causal gene and cell type. Here, we performed paired single nucleus expression chromatin accessibility profiling from 44 human arteries. To link molecular traits, developed a meta-map 88 samples discovered...
Understanding the mechanisms involved in biotransformation of new drugs and their toxicological implications is important for drug development. In this regard, a lot effort has been put into research to recreate liver tissue laboratory purpose screening. This also helped minimize use animal reduce incidence post-market withdrawal drugs. Despite progress made so far, cell source remains major limitation since primary human hepatocytes are scarce various alternatives do not express all genes...