A5059995755- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- RNA modifications and cancer
- Genetic factors in colorectal cancer
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Chromatin Remodeling and Cancer
- Cancer Cells and Metastasis
- Folate and B Vitamins Research
- Pancreatic and Hepatic Oncology Research
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Genetic Syndromes and Imprinting
- Cancer Genomics and Diagnostics
- Birth, Development, and Health
- Bladder and Urothelial Cancer Treatments
- Esophageal Cancer Research and Treatment
- Breast Cancer Treatment Studies
- Metabolism and Genetic Disorders
- Cancer Risks and Factors
- Cancer Treatment and Pharmacology
- Immunotherapy and Immune Responses
- MicroRNA in disease regulation
- Demographic Trends and Gender Preferences
- Ion Channels and Receptors
Duke-NUS Medical School
2016-2023
University of Cambridge
2013-2020
National Centre for Biological Sciences
2009-2010
Tata Institute of Fundamental Research
2009-2010
University of Pennsylvania
2010
Physiological Society
1990
Guy's Hospital
1985-1987
The Honourable Society of Lincoln's Inn
1985
Abstract Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analyzed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined 4 CCA clusters—fluke-positive (clusters 1/2) are enriched ERBB2 amplifications TP53 mutations; conversely, fluke-negative 3/4) exhibit copy-number alterations PD-1/PD-L2 or...
Gastric cancer heterogeneity represents a barrier to disease management. We generated comprehensive single-cell atlas of gastric (>200,000 cells) comprising 48 samples from 31 patients across clinical stages and histologic subtypes. identified 34 distinct cell-lineage states including novel rare cell populations. Many lineage exhibited cancer-associated expression profiles, individually contributing combined tumor-wide molecular collage. observed increased plasma proportions in diffuse-type...
Fetal growth is critically dependent on energy metabolism in the placenta, which drives active exchange of nutrients. Placental oxygen levels are therefore vital, and chronic hypoxia during pregnancy impairs fetal growth. Here we tested hypothesis that placental alters mitochondrial electron transport chain (ETS) function, sought to identify underlying mechanisms. We cultured human cells under different concentrations. Mitochondrial respiration was measured, alongside ETS complexes....
Exportin-1 (XPO1) controls the nucleo-cytoplasmic trafficking of several key growth regulatory and tumor suppressor proteins. Nuclear export blockade through XPO1 inhibition is a target for therapeutic in many cancers. Studies have suggested upregulation as an indicator poor prognosis gastric cancer. In current study, we investigated anti-tumor efficacy selective inhibitors nuclear (SINE) compounds KPT-185, KTP-276 clinical stage selinexor (KPT-330) was found to be overexpressed cancer...
Abstract Background Deregulated gene expression is a hallmark of cancer; however, most studies to date have analyzed short-read RNA sequencing data with inherent limitations. Here, we combine PacBio long-read isoform (Iso-Seq) and Illumina paired-end comprehensively survey the transcriptome gastric cancer (GC), leading cause global mortality. Results We performed full-length analysis across 10 GC cell lines covering four major molecular subtypes (chromosomal unstable, Epstein-Barr positive,...
Abstract Promoter elements play important roles in isoform and cell type–specific expression. We surveyed the epigenomic promoter landscape of gastric adenocarcinoma, analyzing 110 chromatin profiles (H3K4me3, H3K4me1, H3K27ac) primary cancers, cancer lines, nonmalignant tissues. identified nearly 2,000 alterations (somatic promoters), many deregulated various epithelial malignancies mapping frequently to alternative promoters within same gene, generating potential pro-oncogenic isoforms...
Calcium (Ca(2+)) signaling is known to regulate the development, maintenance and modulation of activity in neuronal circuits that underlie organismal behavior. In Drosophila, intracellular Ca(2+) by inositol 1,4,5-trisphosphate receptor store-operated channel (dOrai) regulates formation function control flight. Here, we show restoring InsP(3)R insulin-producing neurons flightless mutants (itpr) during pupal development can rescue systemic flight ability. Expression store operated entry...
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...
The Inositol 1,4,5- trisphosphate receptor (InsP(3)R) is an intracellular ligand gated channel that releases calcium from stores in response to extracellular signals. To identify and understand physiological processes behavior depends on the InsP(3) signaling pathway at a systemic level, we are studying Drosophila mutants for InsP(3)R (itpr) gene. Here, show growth defects precede larval lethality both consequence of inability feed normally. Moreover, restoring function insulin producing...
Folate (folic acid) deficiency and mutations in folate-related genes humans result megaloblastic anaemia. metabolism, which requires the enzyme methionine synthase reductase (MTRR), is necessary for DNA synthesis transmission of one-carbon methyl groups cellular methylation. In this study, we show that hypomorphic Mtrr
Abstract Background CIMP (CpG island methylator phenotype) is an epigenetic molecular subtype, observed in multiple malignancies and associated with the silencing of tumor suppressors. Currently, for most cancers including gastric cancer (GC), mechanisms underlying remain poorly understood. We sought to discover contributors GC, by performing global DNA methylation, gene expression, proteomics profiling across 14 cell lines, followed similar integrative analysis 50 GC lines 467 primary GCs....
Nonalcoholic fatty liver disease (NAFLD) is associated with dietary folate deficiency and mutations in genes required for one‑carbon metabolism. However, the mechanism through which this occurs unclear. To improve our understanding of link, we investigated morphology, metabolism fuel storage adult mice a hypomorphic mutation gene methionine synthase reductase (Mtrrgt). MTRR enzyme key regulator cycles. The Mtrrgt was previously shown to disrupt cause wide-spectrum developmental phenotypes...
The exposure to adverse environmental conditions (e.g. poor nutrition) may lead increased disease risk in an individual and their descendants. In some cases, the results be sexually dimorphic. A range of phenotypes has been associated with deficiency or defective metabolism vitamin folate. However, molecular mechanism linking folate development is still not well defined nor it clear whether are sex-specific. enzyme methionine synthase reductase (MTRR) required for progression utilization...
The effect of temperature on the form propagated action potential was investigated in frog skeletal muscle fibres. Increasing decreased duration initial overshoot but a hump then appeared during more prominent after-depolarization. Finally, at 28-30 degrees C, after-depolarization either noticeably enlarged or entirely absent. This all-or-none failure tubular conduction suggests that excitation membrane takes place through regenerative activity rather than graded electrotonic spread...