A5061591462- Helicobacter pylori-related gastroenterology studies
- Epigenetics and DNA Methylation
- Mycotoxins in Agriculture and Food
- Genomics and Chromatin Dynamics
- Plant Pathogens and Fungal Diseases
- Glaucoma and retinal disorders
- Telomeres, Telomerase, and Senescence
- Genetic Syndromes and Imprinting
- Plant Disease Resistance and Genetics
- RNA Research and Splicing
- Eosinophilic Esophagitis
- Genetics and Neurodevelopmental Disorders
- Mitochondrial Function and Pathology
- Cancer-related gene regulation
- RNA modifications and cancer
- Genetic Neurodegenerative Diseases
- Prenatal Screening and Diagnostics
- Genomics and Rare Diseases
- Whipple's Disease and Interleukins
- Aquaculture disease management and microbiota
- Cancer-related molecular mechanisms research
- Plant Pathogens and Resistance
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Fungal Biology and Applications
- Retinal Diseases and Treatments
University of Ottawa
2017-2024
Children's Hospital of Eastern Ontario
2017-2024
International University of Health and Welfare
2021-2024
University of Tsukuba
2024
Cancer Research UK
2009-2021
University of Cambridge
2009-2021
Newborn Screening Ontario
2020
Université de Montréal
2015-2018
Cancer Research UK Cambridge Center
2008-2017
Waseda University
2000-2017
Cohesin is a chromatin-associated protein complex that mediates sister chromatid cohesion by connecting replicated DNA molecules. also has important roles in gene regulation, but the mechanistic basis of this function poorly understood. In mammalian genomes, cohesin co-localizes with CCCTC binding factor (CTCF), zinc finger implicated multiple regulatory events. At imprinted IGF2-H19 locus, CTCF plays an role organizing allele-specific higher-order chromatin conformation and functions as...
Environmental factors interact with the genome throughout life to determine gene expression and, consequently, tissue function and disease risk. One such factor that is known play an important role in determining long-term metabolic health diet during critical periods of development. Epigenetic regulation has been implicated mediating these programming effects early diet. The precise epigenetic mechanisms underlie remain largely unknown. Here, we show transcription Hnf4a , which etiology...
<h3>Background and aims</h3> Although aberrant methylation of key genes in the progression colorectal neoplasia has been reported, no model-based analysis incremental changes through intermediate adenoma stage described. In addition, biological drivers for these have yet to be defined. Linear mixed-effects modelling was used this study understand onset patterns <i>SFRP2</i>, <i>IGF2</i> DMR0, <i>H19</i>, <i>LINE-1</i> a CpG island methylator phenotype (CIMP) marker panel, they were...
Senescent cells trigger their own immune-mediated destruction, termed senescence surveillance. This is dependent on the inflammatory senescence-associated secretory phenotype (SASP), which includes COX2, an enzyme with complex roles in cancer. The role COX2 plays during surveillance unknown. Here, we show that RAS-induced (RIS), a critical regulator of SASP composition and vivo. regulates expression multiple components through autocrine feedback loop involving its downstream product,...
AbstractA new aflatoxigenic species of Aspergillus, A. bombycis, was discovered during isolation fungi from insect frass collected in silkworm rearing houses Japan. The resembles flavus, but produces B and G aflatoxins. It is distinguished flavus nomius by differences growth rates at 37 42 C, roughness the stipe, both these nucleotide sequences beta-tubulin, calmodulin, norsolorinic acid reductase, ITS, lsu-rDNA genes. Aspergillus bombycis known nine isolates, eight silkworm-rearing Japan...
Around 25-40% of cases hereditary diffuse gastric cancer (HDGC) are caused by heterozygous E-cadherin (CDH1) germline mutations. The mechanisms for loss the second allele still remain unclear. aims this study were to elucidate somatic inactivation wild-type CDH1 and seek evidence cadherin switching. Archival tumour material was analysed from 16 patients with mutations seven fulfilling HDGC criteria without exons sequenced. promoter methylation bisulphite sequencing pyrosequencing specificity...
The imprinted insulin-like growth factor 2 (IGF2) gene is expressed predominantly from the paternal allele. Loss of imprinting (LOI) associated with hypomethylation at promoter proximal sequence (DMR0) IGF2 was proposed as a predisposing constitutive risk biomarker for colorectal cancer. We used pyrosequencing to assess whether DMR0 methylation either present constitutively prior cancer or it acquired tissue-specifically after onset DNA samples tumour tissues and matched non-tumour 22 breast...
Differentially methylated regions (DMRs) are associated with many imprinted genes. In mice methylation at a DMR upstream of the H19 gene known as Imprint Control region (IC1) is acquired in male germline and influences status DMRs 100 kb away adjacent Insulin-like growth factor 2 (Igf2) through long-range interactions. humans, germline-derived or post-zygotically imprinting defects IC1 aberrant activation repression IGF2, resulting congenital disorders Beckwith-Wiedemann (BWS) Silver-Russell...
Genomic imprinting is a normal process that causes genes to be expressed according parental origin. The selective advantage conferred by not understood but hypothesised act on dosage-critical genes. Here, we report unique model in which the consequences of single, double, and triple dosage imprinted Dlk1/Pref1, normally repressed maternally inherited chromosome, can assessed growing embryo. BAC-transgenic mice were generated over-express Dlk1 from endogenous regulators at all sites embryonic...
Hyper- and hypomethylation at the IGF2-H19 imprinting control region (ICR) result in reciprocal changes expression two contrasting growth disorders, Beckwith-Wiedemann syndrome (BWS) Silver-Russell (SRS). DNA methylation of ICR controls IGF2 H19 by preventing binding insulator protein, CTCF. We here show that local histone modifications CTCF--cohesin BWS SRS together with correlate higher order chromatin structure locus. In lymphoblastoid cells from individuals, we found repressive H3K9me3...
Abstract Long noncoding RNAs (lncRNAs) regulate gene expression via their RNA product or through transcriptional interference, yet a strategy to differentiate these two processes is lacking. To address this, we used multiple small interfering (siRNAs) silence GNG12-AS1 , nuclear lncRNA transcribed in an antisense orientation the tumour-suppressor DIRAS3 . Here show that while most siRNAs post-transcriptionally, siRNA complementary exon 1 of suppresses its transcription by recruiting...
Background MicroRNA (miRNA) is an emerging subclass of small non-coding RNAs that regulates gene expression and has a pivotal role for many physiological processes including cancer development. Recent reports revealed the miRNAs as ideal biomarkers therapeutic targets due to their tissue- or disease-specific nature. Head neck (HNC) major cause cancer-related mortality morbidity, laryngeal highest incidence in it. However, molecular mechanisms involved development remain be known highly...
Biallelic pathogenic variants in PLPBP (formerly called PROSC) have recently been shown to cause a novel form of vitamin B6-dependent epilepsy, the pathophysiological basis which is poorly understood. When left untreated, disease can progress status epilepticus and death infancy. Here we present 12 previously undescribed patients six PLPBP. Suspected clinical diagnoses prior identification included mitochondrial encephalopathy (two patients), folinic acid-responsive epilepsy (one patient)...
The discovery of cytosine hydroxymethylation (5hmC) as a mechanism that potentially controls DNA methylation changes typical neoplasia prompted us to investigate its behaviour in colon cancer. 5hmC is globally reduced proliferating cells such tumours and the gut crypt progenitors, from which can arise. Here, we show colorectal cancer express Ten-Eleven-Translocation (TET) transcripts at levels similar normal tissues. Genome-wide analyses promoters marked by tissue, those identified TET2...
The use of rodent models glaucoma has been essential to understand the molecular mechanisms that underlie pathophysiology this multifactorial neurodegenerative disease. With advent numerous transgenic mouse lines, there is increasing interest in inducible murine ocular hypertension. Here, we present an occlusion model based on injection magnetic microbeads into anterior chamber eye using a modified microneedle with facetted bevel. are attracted iridocorneal angle handheld magnet block...
Senescence is a state of stable proliferative arrest, generally accompanied by the senescence-associated secretory phenotype, which modulates tissue homeostasis. Enhancer-promoter interactions, facilitated chromatin loops, play key role in gene regulation but their relevance senescence remains elusive. Here, we use Hi-C to show that oncogenic RAS-induced human diploid fibroblasts extensive enhancer-promoter rewiring, closely connected with dynamic cohesin binding genome. We find de novo...
Poly(ADP-ribosyl)ation of the conserved multifunctional transcription factor CTCF was previously identified as important to maintain insulator and chromatin barrier functions. However, molecular mechanism this regulation also necessity modification for other functions remain unknown. In study, we potential sites poly(ADP-ribosyl)ation within N-terminal domain generated a mutant deficient in poly(ADP-ribosyl)ation. Using mutant, demonstrated requirement optimal function transcriptional...