A5040898168- Metabolism, Diabetes, and Cancer
- CRISPR and Genetic Engineering
- Congenital heart defects research
- Cancer-related molecular mechanisms research
- Diet and metabolism studies
- Animal Genetics and Reproduction
- RNA modifications and cancer
- RNA Interference and Gene Delivery
- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- RNA Research and Splicing
- Hormonal Regulation and Hypertension
- PI3K/AKT/mTOR signaling in cancer
- Cardiac electrophysiology and arrhythmias
- Epigenetics and DNA Methylation
- Pharmacogenetics and Drug Metabolism
- Cancer, Hypoxia, and Metabolism
- Genetic factors in colorectal cancer
- Genomics and Chromatin Dynamics
- MicroRNA in disease regulation
- Colorectal Cancer Treatments and Studies
- Circular RNAs in diseases
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer Genomics and Diagnostics
- RNA and protein synthesis mechanisms
National University Health System
2016-2024
Genome Institute of Singapore
2016-2024
National University of Singapore
2016-2024
Agency for Science, Technology and Research
2016-2022
National University Heart Centre Singapore
2020
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...
Abstract Hepatocellular carcinoma (HCC) has one of the poorest survival rates among cancers. Using multi-regional sampling nine resected HCC with different aetiologies, here we construct phylogenetic relationships these sectors, showing diverse levels genetic sharing, spanning early to late diversification. Unlike variegated pattern found in colorectal cancers, a large proportion display clear isolation-by-distance where spatially closer sectors are genetically more similar. Two...
Abstract Human pluripotent stem cells (hPSCs)-derived cardiovascular progenitor (CVPCs) are a promising source for myocardial repair, while the mechanisms remain largely unknown. Extracellular vesicles (EVs) known to mediate cell–cell communication, however, efficacy and of hPSC-CVPC-secreted EVs (hCVPC-EVs) in infarct healing when given at acute phase infarction (MI) Here, we report cardioprotective effects secreted from hESC-CVPCs under normoxic (EV-N) hypoxic (EV-H) conditions infarcted...
Cardiac regeneration may revolutionize treatment for heart failure but endogenous progenitor-derived cardiomyocytes in the adult mammalian are few and pre-existing divide only at very low rates. Although candidate genes that control cardiomyocyte cell cycle re-entry have been implicated, expression heterogeneity stress-response has never explored. Here, we show by single nuclear RNA-sequencing of from both mouse human failing, non-failing hearts sub-populations upregulate activators...
Abstract Aldosterone-producing adenomas (APAs) are the commonest curable cause of hypertension. Most have gain-of-function somatic mutations ion channels or transporters. Herein we report discovery, replication and phenotype in neuronal cell adhesion gene CADM1 . Independent whole exome sequencing 40 81 APAs found intramembranous p.Val380Asp p.Gly379Asp variants two patients whose hypertension periodic primary aldosteronism were cured by adrenalectomy. Replication identified more with each...
Selection of the target site is an inherent question for any project aiming directed transgene integration. Genomic safe harbour (GSH) loci have been proposed as sites in human genome Although several characterised integration literature, most these do not meet criteria set out a GSH and limited that extensively. Here, we conducted computational analysis using publicly available data to identify 25 unique putative reside active chromosomal compartments. We validated stable expression minimal...
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...
Adult mammalian cardiomyocytes have limited proliferative capacity, but in specifically induced contexts they traverse through cell-cycle reentry, offering the potential for heart regeneration. Endogenous cardiomyocyte proliferation is preceded by dedifferentiation (CMDD), wherein adult revert to a less matured state that distinct from classical myocardial fetal stress gene response associated with failure. However, very little known about CMDD as defined cell transition.
There is increasing preclinical evidence suggesting that metformin, an antidiabetic drug, has anticancer properties against various malignancies, including colorectal cancer. However, the majority of evidence, which was derived from cancer cell lines and xenografts, likely to overestimate benefit metformin because these models are inadequate require supraphysiologic levels metformin. Here, we generated patient-derived xenograft (PDX) 2 patients assess 5-fluorouracil (5-FU), first-line drug...
Objective Use next-generation sequencing (NGS) technology to improve our diagnostic yield in patients with suspected genetic disorders the Asian setting. Design A study conducted between 2014 and 2019 (and ongoing) under Singapore Undiagnosed Disease Program. Date of last analysis was 1 July 2019. Setting Inpatient outpatient genetics service at two large academic centres Singapore. Patients Inclusion criteria: disorders, based on abnormal antenatal ultrasound, multiple congenital anomalies...
In Western cohorts, the prevalence of incidental findings (IFs) or incidentalome, referring to variants in genes that are unrelated patient's primary condition, is between 0.86% and 8.8%. However, data on type IFs Asian population lacking.In 2 cohorts individuals with genomic sequencing performed Singapore (total n = 377), we extracted annotated 56 ACMG-recommended filtered these based level pathogenicity. We then analyzed precise distribution IFs, class genes, related medical conditions,...
Although bulk high-throughput genomic profiling studies have led to a significant increase in the understanding of cancer biology, there is increasing awareness that approaches do not completely elucidate tumor heterogeneity. Single-cell enables distinction heterogeneity, and may improve clinical diagnosis through identification characterization putative subclonal populations. In present study, challenges associated with single-cell genomics workflow for diagnostics were investigated....
Abstract Background Biomechanical stimuli are known to be important cardiac development, but the mechanisms not fully understood. Here, we pharmacologically disrupted biomechanical environment of wild‐type zebrafish embryonic hearts for an extended duration and investigated consequent effects on function, morphological gene expression. Results Myocardial contractility was significantly diminished or abolished in treated 72 hours from 2 dpf with 2,3‐butanedione monoxime (BDM). Image‐based...
Direct cardiac reprogramming represents an attractive way to reversing heart damage caused by myocardial infarction because it removes fibroblasts, while also generating new functional cardiomyocytes. Yet, the main hurdle for bringing this technique clinic is lack of efficacy with current protocols. Here, we describe our unexpected discovery that DMSO capable significantly augmenting direct in vitro.Upon induction transcription factors- Gata4, Hand2, Mef2c and Tbx5 (GHMT), treatment mouse...
Abstract The Peranakan Chinese are culturally unique descendants of immigrants from China who settled in the Malay Archipelago ∼300–500 years ago. Today, among large communities Southeast Asia, Peranakans have preserved traditions with strong influence local indigenous Malays. Yet, whether or to what extent genetic admixture co-occurred cultural mixture has been a topic ongoing debate. We performed whole-genome sequencing (WGS) on 177 Singapore (SG) and analyzed data jointly WGS Asian...
The mammalian genome is coiled, compacted and compartmentalized into complex non-random three-dimensional chromatin loops in the nucleus 1–3 . At core of loop formation CCCTC-binding factor (CTCF), also described as a “weaver genome” 45 Anchored by CTCF, are proposed to form through extrusion process 6 , organising themselves gene neighbourhoods 2 that harbour insulated enhancer-promoter domains, restricting enhancer activities genes within loops, insulating from promiscuous interactions...
Doxorubicin is an anthracycline widely used for the treatment of various cancers; however, drug has a common deleterious side effect, namely dose-dependent cardiotoxicity. increases generation reactive oxygen species, which leads to oxidative stress in cardiac cells and ultimately DNA damage cell death. The most lesion produced by 7,8-dihydro-8-oxoguanine (8-oxoguanine), enzyme responsible its repair 8-oxoguanine glycosylase (OGG1), base excision enzyme. Here, we show that OGG1 deficiency no...
Rationale: Cardiac-expressed long noncoding RNAs (lncRNAs) are important for cardiomyocyte (CM) differentiation and function. Several lncRNAs have been identified characterized early CM lineage commitment, however those in later specification maturation remain less well studied. Moreover, distinctive atrial / ventricular lncRNA expression is still not widely analysed detail.Objectives: Here, we a novel myocyte-restricted lncRNA, expressed cardiomyocytes, conserved only primates.Methods...
Abstract Background Long noncoding RNAs (lncRNAs) control early stages of cardiac differentiation, however their role in later specification and maturation is still not well explored. Methods results We performed single cell RNA-seq for 2, 6 12 week-old hESC-CM. Weighted correlation network analysis (WGCNA) identified core genes significantly upregulated, along with a subset lncRNAs. Importantly, these lncRNAs are highly abundant unique to human heart. Through independent integrative...
ABSTRACT Rationale Long noncoding RNAs (lncRNAs) control cardiac gene expression during heart development and disease. It is accordingly plausible for the same lncRNA to regulate both development, as well play a role in adult disease progression. regulators of early cardiomyocyte (CM) lineage commitment have been identified characterised, however those controlling later CM specification remain unknown. Objectives In this study we novel required specification, maturation function, also...