A5085022063- Cell Adhesion Molecules Research
- Cancer Genomics and Diagnostics
- Gene expression and cancer classification
- RNA modifications and cancer
- Protease and Inhibitor Mechanisms
- Cancer-related molecular mechanisms research
- Lysosomal Storage Disorders Research
- Proteoglycans and glycosaminoglycans research
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Platelet Disorders and Treatments
- Genomics and Chromatin Dynamics
- Molecular Biology Techniques and Applications
- Genomic variations and chromosomal abnormalities
- Biochemical and Molecular Research
- Cytomegalovirus and herpesvirus research
- Single-cell and spatial transcriptomics
- Head and Neck Cancer Studies
- HER2/EGFR in Cancer Research
- MicroRNA in disease regulation
- Genetic Neurodegenerative Diseases
- Poxvirus research and outbreaks
- Enzyme Production and Characterization
- Genetic Syndromes and Imprinting
- Mitochondrial Function and Pathology
National University of Singapore
2024-2025
Stanford University
2012-2023
Stratford University
2023
University Medical Center
2023
University Hospital and Clinics
2023
Sanofi (United States)
2020
ORCID
2020
Douglas Mental Health University Institute
2013-2019
McGill University
2013-2019
Stanford Medicine
2010
Abstract Background Molecular characterization of tumors has been critical for identifying important genes in cancer biology and improving tumor classification diagnosis. Long non-coding RNAs, as a new, relatively unstudied class transcripts, provide rich opportunity to identify both functional drivers cancer-type-specific biomarkers. However, despite the potential importance long RNAs field, no comprehensive survey RNA expression across various cancers reported. Results We performed...
Gene expression microarrays are the most widely used technique for genome-wide profiling. However, do not perform well on formalin fixed paraffin embedded tissue (FFPET). Consequently, cannot be effectively utilized to gene profiling vast majority of archival tumor samples. To address this limitation microarrays, we designed a novel procedure (3′-end sequencing quantification (3SEQ)) from FFPET using next-generation sequencing. We performed by 3SEQ and microarray both frozen two soft tumors...
RNA sequencing (RNA-seq) is a sensitive and accurate method for quantifying gene expression. Small samples or those whose degraded, such as formalin-fixed paraffin-embedded (FFPE) tissue, remain challenging to study with nonspecialized RNA-seq protocols. Here, we present new method, Smart-3SEQ, that accurately quantifies transcript abundance even small amounts of total effectively characterizes extracted by laser-capture microdissection (LCM) from FFPE tissue. We also obtain distinct...
Liver-directed gene therapy with adeno-associated virus (AAV) vectors effectively treats mouse models of lysosomal storage diseases (LSDs). We asked whether these results were likely to translate patients. To understand what extent preexisting anti-AAV8 antibodies could impede AAV8-mediated liver transduction in primates, commonly preexposed AAV, we quantified the effects on and subsequent transgene expression nonhuman primate (NHP) models. Using highest viral dose previously reported a...
The contribution of pre-mRNA processing mechanisms to the regulation immune responses remains poorly studied despite emerging examples their role as regulators defenses. We sought investigate mRNA in cellular human macrophages live bacterial infections. Here, we used sequencing quantify gene expression and isoform abundances primary from 60 individuals, before after infection with Listeria monocytogenes Salmonella typhimurium. In response both bacteria identified thousands genes that...
ABSTRACT Streptococcus pneumoniae is an important human pathogen that contains single copies of genes encoding the ClpP and FtsH ATP-dependent proteases but lacks Lon HslV proteases. We constructed characterized phenotypes clpP , clpC clpX deletion replacement mutants, which lack protease subunit or putative ClpC ClpX ATPase specificity factor. A Δ mutant, not a virulent D39 type 2 strain S. grew poorly at 30°C failed to grow 40°C. Despite this temperature sensitivity, transcription heat...
ABSTRACT A noninvasive, real-time detection technology was validated for qualitative and quantitative antimicrobial treatment applications. The lux gene cluster of Photorhabdus luminescens introduced into an Escherichia coli clinical isolate, EC14, on a multicopy plasmid. This bioluminescent reporter bacterium used to study effects in vitro vivo, using the neutropenic-mouse thigh model infection. Bioluminescence monitored measured vivo with intensified charge-coupled device (ICCD) camera...
Abstract Anti-PD1 therapy in nasopharyngeal carcinoma (NPC) demonstrates limited efficacy, with only 19.3% of patients achieving one-year progression-free survival. Identifying predictive biomarkers is crucial for enhancing therapeutic outcomes. Endoplasmic reticulum aminopeptidase 2 (ERAP2), an enzyme involved MHC Class I peptide processing, has been implicated immune evasion mechanisms. We analyzed a cohort 10 recurrent/metastatic NPC treated anti-PD-1 therapy. Tumor epithelial and...
Niemann-Pick disease (NPD) is caused by the loss of acid sphingomyelinase (ASM) activity, which results in widespread accumulation undegraded lipids cells viscera and CNS. In this study, we tested effect combination brain systemic injections recombinant adeno-associated viral vectors encoding human ASM (hASM) a mouse model NPD. Animals treated therapy exhibited high levels hASM brain, resulted near-complete correction storage throughout body. This global reversal pathology translated to...
The availability of a murine model Pompe disease has enabled an evaluation the relative merits various therapeutic paradigms, including gene therapy. We report here that administration recombinant adeno-associated virus serotype 8 (AAV8) vector (AAV8/DC190-GAA) encoding human acid alpha-glucosidase (GAA) into presymptomatic mice resulted in nearly complete correction lysosomal storage glycogen all affected muscles. A relatively high dose AAV8/DC190-GAA was necessary to attain threshold level...
Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptoms in men. Current treatments target prostate physiology rather than BPH pathophysiology and are only partially effective. Here, we applied next-generation sequencing to gain new insight into BPH. By RNAseq, uncovered transcriptional heterogeneity among cases, where a 65-gene stromal signature correlated with symptom severity. Stromal signaling molecules BMP5 CXCL13 were enriched while estrogen regulated...
High-occupancy target (HOT) regions are compact genome loci occupied by many different transcription factors (TFs). HOT were initially defined in invertebrate model organisms, and we here show that they a ubiquitous feature of the human gene-regulation landscape.We identified comprehensive analysis ChIP-seq data from 96 DNA-associated proteins 5 cell lines. Most co-localize with RNA polymerase II binding sites, but not near promoters annotated genes. At promoters, TF occupancy is strongly...
In embryonic stem cells, extracellular signals are required to derepress developmental promoters drive lineage specification, but the proteins involved in connecting extrinsic cues relaxation of chromatin remain unknown. We demonstrate that helix-loop-helix (HLH) protein, HEB, directly associates with Polycomb repressive complex 2 (PRC2) at a subset promoters, including genes mesoderm and endoderm specification Hox Fox gene families. While we show depletion HEB does not affect mouse ESCs, it...
Nasopharyngeal cancer (NPC) is an Epstein-Barr virus (EBV)–positive epithelial malignancy with extensive inflammatory infiltrate. Traditional RNA-sequencing techniques uncovered only microenvironment signatures, while the gene expression of tumor compartment has remained a mystery. Here, we use Smart-3SEQ to prepare transcriptome-wide profiles from microdissected NPC tumors, dysplasia, and normal controls. We describe changes in biological pathways across spectrum show that fibroblast growth...
Using immunohistochemistry and competitive PCR for collagen types XII XIV, we have followed the expression of these fibril-associated molecules during development avian cornea. By immunofluorescence histochemistry, both are found in acellular primary stroma therefore presumably epithelial origin. During formation secondary corneal stroma, which is populated by mesenchymal cells, generally appear to be spatially segregated from each other. Type XIV throughout most predominantly a product...
Bowman's membrane is an acellular matrix of the cornea which lies between epithelial basal lamina and corneal stroma. By immunoelectron microscopy, we have determined that types I V collagen are components fibrils in chick cornea. Although these same found stroma, smaller diameter less uniform than those At early stages development, epithelium synthesizes II primary We therefore asked whether it might also be capable synthesizing type at later development. Our results, using competitive...
Peripheral neuropathy is a particularly debilitating complication of both type 1 and 2 diabetes characterized by sensory motor neuron damage decreased circulating levels insulin-like growth factor (IGF-1). Quite often, an early hyperalgesia followed hypoalgesia muscle weakness. Hypoalgesia can lead to significant morbidity for which there no current treatment. Hyperglycemic, streptozotocin (STZ)-induced rodent models reproduce these symptoms. We investigated whether increasing systemic IGF-1...
The combined nucleotide sequences of several overlapping cDNAs provide the first complete amino acid sequence type XIV collagen.Independent confirmation deduced is provided by sequencing tryptic peptides isolated from purified chicken skin collagen.Com- parative analyses show that amino-terminal nontriple-helical region al(X1V) chains contains se- quence motifs are similar to al(1X) collagen, fibronectin 111 repeats, and von Willebrand's factor A-domains.The results also strongly suggest...
Fas ligand (FasL)-induced lung inflammation has recently been suggested to play an important role in the pathogenesis of acute respiratory disease syndrome (ARDS). In order further explore this connection, we established a FasL-induced murine model pulmonary inflammation. Instillation recombinant FasL (rFasL) into induced neutrophil infiltration and increased permeability, as evidenced by total protein airspace; both occur patients with ARDS. These effects were accompanied rapid induction...
Abstract Mutations at the APM1 and APM2 loci in green alga Chlamydomonas reinhardtii confer resistance to phosphorothioamidate dinitroaniline herbicides. Genetic interactions between apm1 apm2 mutations suggest an interaction gene products. We identified genes using a map-based cloning strategy. Genomic DNA fragments containing only DNJ1 encoding type I Hsp40 protein rescue mutant phenotypes, conferring sensitivity herbicides rescuing temperature-sensitive growth defect. Lesions five alleles...
Due to the lack of acid alpha-glucosidase (GAA) activity, Pompe mice develop glycogen storage pathology and progressive skeletal muscle dysfunction with age. Applying either gene or enzyme therapy reconstitute GAA levels in older, symptomatic effectively reduces but provides only modest improvements motor function. As strategies stimulate hypertrophy, such as by myostatin inhibition, have been shown improve strength mouse models muscular dystrophy, we sought determine whether these benefits...
Herpes simplex virus 1 (HSV-1) infects skin and mucosal epithelial cells then travels along axons to establish latency in the neurones of sensory ganglia. Although viral gene expression is restricted during latency, latency-associated transcript (LAT) locus encodes many RNAs, including a 2 kb intron known as hallmark HSV-1 latency. Here, we studied infection role LAT human xenografts vivo cultured explants. We sequenced genomes our stock strain 17s yn + seven derived viruses found...
ABSTRACT The contribution of pre-mRNA processing mechanisms to the regulation immune responses remains poorly studied despite emerging examples their role as regulators defenses. Here, we used mRNA sequencing quantify gene expression and isoform abundances in primary macrophages from 60 individuals, before after infection with two live bacteria. In response both bacteria identified thousands genes that significantly change usage infection, found global shifts towards ( i ) inclusion cassette...