A5023396611- Acute Myeloid Leukemia Research
- Genomics and Rare Diseases
- Ion channel regulation and function
- RNA regulation and disease
- Cell Image Analysis Techniques
- Genetic and Kidney Cyst Diseases
- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neuropharmacology Research
- Hedgehog Signaling Pathway Studies
- Wnt/β-catenin signaling in development and cancer
- Genomic variations and chromosomal abnormalities
- Cell Adhesion Molecules Research
- Plant Pathogenic Bacteria Studies
- Bone and Joint Diseases
- Epigenetics and DNA Methylation
- Connective tissue disorders research
- Lymphoma Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Cellular transport and secretion
- Morphological variations and asymmetry
- Congenital limb and hand anomalies
- Hippo pathway signaling and YAP/TAZ
- Cardiac electrophysiology and arrhythmias
- Neurological diseases and metabolism
- Genetic Syndromes and Imprinting
National University Hospital
2018-2025
Singapore Institute of Technology
2024
National University Health System
2020-2024
Institute of Molecular and Cell Biology
2005-2023
Agency for Science, Technology and Research
2014-2023
National Skin Centre
2020
National University of Singapore
2003-2019
Isfahan University of Medical Sciences
2019
Shahid Beheshti University of Medical Sciences
2019
Jinan University
2019
Abstract Reports linking long-term use of bisphosphonates (BPs) with atypical fractures the femur led leadership American Society for Bone and Mineral Research (ASBMR) to appoint a task force address key questions related this problem. A multidisciplinary expert group reviewed pertinent published reports concerning fractures, as well preclinical studies that could provide insight into their pathogenesis. case definition was developed so subsequent report on same condition. The defined major...
Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand molecular mechanisms underlying cichlid phenotypic diversity, we sequenced genomes transcriptomes five lineages African cichlids: Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; four members lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent Malawi), Pundamilia nyererei (very recent...
Highlights•A CRISPR-Cas9 and PiggyBac-based approach allows efficient correction of HD hiPSCs•The corrected hiPSCs can be differentiated into synaptically active neurons•Correction gene mutation reverses a number phenotypic abnormalities•Isogenic help distinguish from genetic background-related effectsSummaryHuntington disease (HD) is dominant neurodegenerative disorder caused by CAG repeat expansion in HTT. Here we report human induced pluripotent stem cells (hiPSCs) using piggyBac...
The bacterial pathogen Xanthomonas campestris pv. co-ordinates virulence factor production and biofilm dispersal through a diffusible signal (DSF)-mediated cell-cell communication mechanism. RpfC/RpfG two-component system plays key role in DSF transduction appears to modulate downstream regulon by changing intracellular content of cyclic dimeric GMP (c-di-GMP), an unusual nucleotide second messenger. Here we show that Clp, conserved global regulator showing strong homology the cAMP receptor...
The bacterial pathogen Xanthomonas campestris pv. (Xcc) recruits a diffusible signal factor (DSF), which has recently been structurally characterized as cis-11-methyl-2-dodecenoic acid, cell-cell communication to synchronize virulence gene expression and biofilm dispersal. In this study, we showed that despite the existance of phenotype variations in different Xcc isolates, DSF-mediated functions were general conserved. To investigate genomic profiles DSF regulation, designed conducted...
Abstract Developmental epileptic encephalopathies are devastating disorders characterized by intractable seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH 36 cases from 25 families presenting with encephalopathy delay hypotonia. encodes oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component specific proteoglycans glycolipids. Consistent being loss-of-function alleles, show using patients’ primary fibroblasts...
Failure of neural tube closure during embryonic development can result in anencephaly, one the most common birth defects humans. A family with recurrent anencephalic fetuses was investigated to understand its etiology and pathogenesis. Exome sequencing revealed a recessive germline 21-bp in-frame deletion NUAK2 segregating disease. In vitro kinase assays demonstrated that 7–amino acid truncation NUAK2, serine/threonine kinase, completely abrogated catalytic activity. Patient-derived disease...
Alport syndrome is a common monogenic kidney disease resulting from pathogenic variants in COL4A3, COL4A4 or COL4A5 genes. The estimated global population prevalence one 106 individuals for autosomal dominant (AD) and 2,320 sex-linked (XL) conditions. Here, we aimed to estimate the of carrying that cause Singapore, stratify by ancestry. We used population-scale genomic data 9,051 unrelated subjects, comprising 5,443 (60.8%) Chinese, 1,922 (21.4%) Indian 1,686 (17.8%) Malay individuals. with...
Endocrine-cerebro-osteodysplasia (ECO) syndrome [MIM:612651] caused by a recessive mutation (p.R272Q) in Intestinal cell kinase (ICK) shows significant clinical overlap with ciliary disorders. Similarities are strongest between ECO syndrome, the Majewski and Mohr-Majewski short-rib thoracic dysplasia (SRTD) polydactyly syndromes, hydrolethalus syndrome. In this study, we present novel homozygous ICK fetus compare effect of previously reported variant on ciliogenesis cilium morphology....
RGK proteins (Kir/Gem, Rad, Rem, and Rem2) form a small subfamily of the Ras superfamily. Despite conserved GTP binding core domain, several differences suggest that structure, mechanism action, functional regulation differ from Ras. down-regulate voltage-gated calcium channel activity by in GTP-dependent fashion to Cavβ subunits. Mutational analysis combined with homology modeling reveal novel effector distinct other GTPases. In this model Switch 1 region acts as an allosteric activator...
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...
Abstract Ermin is an actin‐binding protein found almost exclusively in the central nervous system (CNS) as a component of myelin sheaths. Although has been predicted to play role formation and stability sheaths, this not directly examined vivo. Here, we show that essential for sheath integrity normal saltatory conduction. Loss mice caused de‐compacted fragmented sheaths led slower conduction along with progressive neurological deficits. RNA sequencing corpus callosum, largest white matter...
Abstract Multinational studies have reported monogenic etiologies in 25%–30% of children with steroid‐resistant nephrotic syndrome. Such large are lacking Asia. We established Deciphering Diversities: Renal Asian Genetics Network (DRAGoN) and aimed to describe the genetic clinical spectrums Asians. prospectively studied a cohort 183 probands suspected glomerulopathies from South Southeast Asia, whom 17% had positive family history. Using multi‐gene panel sequencing, we detected pathogenic...
Abstract Developmental studies have shown that the evolutionarily conserved Wnt Planar Cell Polarity (PCP) pathway is essential for development of a diverse range tissues and organs including brain, spinal cord, heart sensory organs, as well establishment left-right body axis. Germline mutations in highly PCP gene VANGL2 humans only been associated with central nervous system malformations, functional testing to understand variant impact has not performed. Here we report three new families...
Prk1p is a serine/threonine kinase involved in the regulation of actin cytoskeleton organization yeast Saccharomyces cerevisiae. Previously, we have identified LxxQxTG as phosphorylation site Prk1p. In this report, recognition sequence for investigated more thoroughly. It found that presence hydrophobic residue at position P-5 necessary and L, I, V, M are all able to confer various efficiencies. The flexibility P-2 has also been include Q, N, T, S. A homology-based three-dimensional model...
Background Body fatness is associated with risk of coronary heart disease and it has been postulated that epicardial adipose tissue (EAT) may have a particularly detrimental effect because its localized toxic effects. We therefore aimed to examine the association between EAT artery calcification compared this associations for visceral (VAT) other regional fat depots. Methods conducted cross-sectional study 487 Chinese participants aged 50 years old above, living in Singapore. Participants,...
Voltage-gated calcium channels (VGCCs) are key regulators of cell signaling and Ca2+-dependent release neurotransmitters hormones. Understanding the mechanisms that inactivate VGCCs to prevent intracellular Ca2+ overload govern their specific subcellular localization is critical importance. We report identification functional characterization VGCC β-anchoring -regulatory protein (BARP), a previously uncharacterized integral membrane glycoprotein expressed in neuroendocrine cells neurons....
The authors present an unsupervised, scalable, and interpretable cell profiling framework that is compatible with data gathered from high-content screening. They demonstrate the effectiveness of their by modeling drug differential effects IC-21 macrophages treated microtubule actin disrupting drugs. identify significant features phenotypes for unsupervised learning based on maximum relevancy minimum redundancy criteria. A 2-stage clustering approach annotates, clusters cells, then merges...