A5061007676- Autophagy in Disease and Therapy
- Cancer Genomics and Diagnostics
- Calcium signaling and nucleotide metabolism
- Epigenetics and DNA Methylation
- Cellular transport and secretion
- Endoplasmic Reticulum Stress and Disease
- Immune Response and Inflammation
- Neonatal Respiratory Health Research
- RNA modifications and cancer
- Infant Nutrition and Health
- Lysosomal Storage Disorders Research
- Single-cell and spatial transcriptomics
- Genetic factors in colorectal cancer
- Ubiquitin and proteasome pathways
- Oral microbiology and periodontitis research
- Preterm Birth and Chorioamnionitis
- Polyamine Metabolism and Applications
- Lung Cancer Treatments and Mutations
- Kawasaki Disease and Coronary Complications
- Environmental DNA in Biodiversity Studies
- Proteoglycans and glycosaminoglycans research
- Plant responses to water stress
- Skin Protection and Aging
- Antimicrobial Peptides and Activities
- Neonatal and Maternal Infections
Genome Institute of Singapore
2021-2025
Agency for Science, Technology and Research
2017-2025
Serdang Hospital
2024
Institute of Medical Biology
2017-2018
Memorial Sloan Kettering Cancer Center
2010-2015
New York Proton Center
2013
Cornell University
2011
The University of Western Australia
2001-2010
National University of Singapore
2008
Graduate School USA
2001
Abstract Autophagy is a cellular catabolic process critical for cell viability and homoeostasis. Inhibition of mammalian target rapamycin (mTOR) complex-1 (mTORC1) activates autophagy. A puzzling observation that amino acid starvation triggers more rapid autophagy than pharmacological inhibition mTORC1, although they both block mTORC1 activity with similar kinetics. Here we find in addition to inactivation, also causes an increase phosphatase towards ULK1, substrate whose dephosphorylation...
Abstract Profiling of circulating tumor DNA (ctDNA) may offer a non-invasive approach to monitor disease progression. Here, we develop quantitative method, exploiting local tissue-specific cell-free (cfDNA) degradation patterns, that accurately estimates ctDNA burden independent genomic aberrations. Nucleosome-dependent cfDNA at promoters and first exon-intron junctions is strongly associated with differential transcriptional activity in tumors blood. A model, based on just 6 regulatory...
Ubiquitin-proteasome system and autophagy are the two major mechanisms for protein degradation in eukaryotic cells. LC3, a ubiquitin-like protein, plays an essential role through its ability to be conjugated phosphatidylethanolamine. In this study, we discovered novel LC3-processing activity, biochemically purified 20S proteasome as responsible enzyme. Processing of LC3 by is ATP- ubiquitin-independent, requires both N-terminal helices ubiquitin fold LC3; addition N terminus renders...
Detection of somatic mutations in cell-free DNA (cfDNA) is challenging due to low variant allele frequencies and pronounced degradation. Here, we present a novel approach resource for benchmarking calling algorithms cfDNA samples from cancer patients. Using longitudinally collected colorectal breast patients, identify patient-matched with high ultra-low circulating tumor (ctDNA) levels. These sample pairs, preserving patient-specific germline haematopoiesis backgrounds, were used generate...
Retinoic acid receptors (RARs) α, β and γ are key regulators of embryonic development. Hematopoietic differentiation is regulated by RARα, several types leukemia show aberrant RARα activity. Through microarray expression analysis, we identified transcripts differentially expressed between F9 wild-type (Wt) knockout cells cultured in the absence or presence RAR-specific ligand all trans retinoic (RA). We validated decreased Mest, Tex13, Gab1, Bcl11a, Tcfap2a HMGcs1 transcript levels,...
Cole disease is a genodermatosis of pigmentation following strict dominant mode inheritance. In this study, we investigated eight patients affected with an overlapping after recessive The presented hypo- and hyperpigmented macules over the body, resembling dyschromatosis universalis hereditaria in addition to punctuate palmoplantar keratosis. By homozygosity mapping whole-exome sequencing, biallelic p.Cys120Arg mutation ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) was...
AbstractA close relationship exists between autophagy and endocytosis with both sharing lysosomes as their common end-point. Autophagy even requires a functional endocytic pathway. The point at which the two pathways merge, i.e., fusion of autophagosomes endosomes is poorly understood. Early work in yeast more recent studies mammalian cells suggested that conventional membrane trafficking control lysosomes; Rab GTPases are required to recruit tethering proteins turn coordinate SNARE family...
The epidermis, outermost layer of the skin, forms a barrier and is involved in innate adaptive immunity an organism. Keratinocytes participate all these three protective processes. However, regulator keratinocyte responses against external dangers stresses remains elusive. We found that upregulation orphan gene 2610528A11Rik was common factor skin mice with several types inflammation. In human peptide expression G protein-coupled receptor 15 ligand (GPR15L), encoded by ortholog C10orf99 ,...
Genome-wide analysis of cell-free DNA methylation profile is a promising approach for sensitive and specific detection many cancers. However, scaling such assays clinical translation impractical because the high cost whole-genome bisulfite sequencing. We show that small fraction GC-rich genome highly enriched in CpG sites disproportionately harbors most cancer-specific signature. Here, we report on simple effective heat enrichment CpG-rich regions sequencing (Heatrich-BS) platform allows...
5-Methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are the most abundant DNA modifications that have important roles in gene regulation. Detailed studies of these different epigenetic marks aimed at understanding their combined effects dynamic interconversion are, however, hampered by inability current methods to simultaneously measure both modifications, particularly samples with limited quantities. We present analysis restriction enzyme for simultaneous detection multiple epigenomic...
Abstract Quantification of circulating tumor DNA (ctDNA) levels in blood enables non-invasive surveillance cancer progression. Fragle is an ultra-fast deep learning-based method for ctDNA quantification directly from cell-free fragment length profiles. We developed using low-pass whole genome sequence (lpWGS) data multiple types and healthy control cohorts, demonstrating high accuracy, improved lower limit detection independent cohorts as compared to existing tumor-naïve methods. Uniquely,...
Abstract Circulating tumour DNA (ctDNA) has emerged as a rich source of biomarkers in precision oncology. However, ctDNA sequence data is often noisier than that derived from standard tissue biopsies, posing significant challenges for accurate cancer mutation detection. Besides, there lack standardised and unbiased benchmark datasets to evaluate compare performance variant callers on ctDNA. To address this issue, we present novel benchmarking approach comprehensive somatic cell-free (cfDNA)...
Ubiquitin‐proteasome system and autophagy are the two major mechanisms for protein degradation in eukaryotic cells. LC3, a ubiquitin‐like protein, plays an essential role through its ability to be conjugated phosphatidylethanolamine. In this study, we discovered novel LC3‐processing activity, biochemically purified 20S proteasome as responsible enzyme. Processing of LC3 by is ATP‐ ubiquitin‐independent, requires both N‐terminal helices ubiquitin fold LC3. The processes stepwise manner, it...