A5074581885- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Genetic Syndromes and Imprinting
- Cancer-related gene regulation
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Chromatin Remodeling and Cancer
- Genomics and Chromatin Dynamics
- Genetic factors in colorectal cancer
- Hemoglobinopathies and Related Disorders
- Congenital heart defects research
- Metabolism and Genetic Disorders
- Autism Spectrum Disorder Research
- Cancer-related molecular mechanisms research
- Iron Metabolism and Disorders
- BRCA gene mutations in cancer
- Mitochondrial Function and Pathology
- Chronic Myeloid Leukemia Treatments
- Tumors and Oncological Cases
- Lymphoma Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
Western University
2016-2025
London Health Sciences Centre
2016-2025
Amsterdam University Medical Centers
2024
University of Amsterdam
2023-2024
Hanover College
2024
University of Wisconsin–Madison
2024
Victoria Hospital
2017-2024
Pitié-Salpêtrière Hospital
2023
Deleted Institution
2021-2023
Sorbonne Université
2023
The cellular mechanism of bioactivation underlying guanylate cyclase activation by organic nitrates was investigated. In cultured rat lung fibroblasts (RFL-6 cells), the inhibitor cytochrome P-450 proadifen (0.1 mM) decreased cyclic GMP stimulation glyceryl trinitrate (GTN, 1-100 microM) up to 81%. Cyclic isoidide dinitrate inhibited a similar degree under these conditions. However, did not affect sodium nitroprusside that spontaneously releases nitric oxide. in RFL-6 cells GTN remained...
PurposeWe describe the clinical implementation of genome-wide DNA methylation analysis in rare disorders across EpiSign diagnostic laboratory network and assessment results impact first subjects tested.MethodsWe outline logistics data flow between an integrated diagnostics laboratories Europe, United States, Canada. We validation using 211 specimens assess test performance yield 207 tested involving two patient subgroups: targeted cohort (subjects with previous ambiguous/inconclusive genetic...
Overlapping clinical phenotypes and an expanding breadth complexity of genomic associations are a growing challenge in the diagnosis management Mendelian disorders. The functional consequences impacts variation may involve unique, disorder-specific, DNA methylation episignatures. In this study, we describe 19 novel episignature disorders compare findings alongside 38 previously established episignatures for total 57 associated with 65 genetic syndromes. We demonstrate increasing resolution...
Both genetic and epigenetic changes contribute to development of human cancer. Oncogenomics has primarily focused on understanding the basis neoplasia, with less emphasis being placed role epigenetics in tumourigenesis. Genomic alterations cancer vary between different types stages, tissues individuals. Moreover, genomic change ranges from single nucleotide mutations gross chromosomal aneuploidy; which may or not be associated underlying instability. Collectively, result widespread...
MicroRNAs (miRs) are non-coding RNA molecules involved in cancer initiation and progression. Deregulated miR expression has been implicated cancer; however, there no studies implicating an signature associated with progression oral squamous cell carcinoma (OSCC). Although OSCC may develop from leukoplakia, clinical histological assessments have limited prognostic value predicting which leukoplakic lesions will progress. Our aim was to quantify changes leukoplakia same-site identify We...
Despite possessing limited protein-coding potential, long non-coding RNAs (lncRNAs) have been implicated in a myriad of pathologic conditions. Most well documented cancer, one prominent intergenic lncRNA known as MALAT1 is notorious for its role impacting epigenetic mechanisms. In this study, we established novel paradigm MALAT diabetic retinopathy (DR) by employing siRNA-mediated knockdown human retinal endothelial cells (HRECs), Malat1 knockout animal model, vitreous humor from patients,...
Abstract Background Human osteosarcoma is the most common pediatric bone tumor. There limited understanding of molecular mechanisms underlying oncogenesis, and a lack good diagnostic as well prognostic clinical markers for this disease. Recent discoveries have highlighted potential role number genes including: RECQL4 , DOCK5 SPP1 RUNX2 RB1 CDKN1A P53 IBSP LSAMP MYC TNFRSF1B BMP2 HISTH2BE FOS CCNB1 CDC5L . Methods Our objective was to assess relative expression levels these 16 biomarkers...
Altered gene expression in tumors can be caused by copy number alterations to DNA or mutation affecting coding regulatory regions of genes. However, epigenetic events may also influence expression. Malignant cells show major disruptions methylation profiles, which are manifested as aberrant hypermethylation hypomethylation promoters, well global genomic hypomethylation. In this study we performed integrative whole-genome analysis number, promoter and using 10 osteosarcomas. We identified...
We recently reported a deletion of exon 2 the trimethyllysine hydroxylase epsilon ( TMLHE ) gene in proband with autism. maps to X chromosome and encodes first enzyme carnitine biosynthesis, 6- N -trimethyllysine dioxygenase. Deletion causes deficiency, resulting increased substrate concentration (6- -trimethyllysine) decreased product levels (3-hydroxy-6- γ-butyrobetaine) plasma urine. deficiency is common control males (24 8,787 or 1 366) was not significantly frequency probands from...
Abstract Coffin–Siris and Nicolaides–Baraitser syndromes (CSS NCBRS) are Mendelian disorders caused by mutations in subunits of the BAF chromatin remodeling complex. We report overlapping peripheral blood DNA methylation epi-signatures individuals with various subtypes CSS ( ARID1B , SMARCB1 SMARCA4 ) NCBRS SMARCA2 ). demonstrate that degree similarity some can be greater than within CSS, indicating a link functional basis two syndromes. show chromosome 6q25 microdeletion syndrome, harboring...
Kabuki syndrome (KS) is caused by mutations in KMT2D, which a histone methyltransferase involved methylation of H3K4, marker associated with DNA methylation. Analysis >450,000 CpGs 24 KS patients pathogenic KMT2D and 216 controls, identified genomic regions, along 1,504 CpG sites significant changes including number Hox genes the MYO1F gene. Using most differentiating probes regions we developed "methylation variant pathogenicity (MVP) score," enables 100% sensitive specific identification...
ADNP syndrome is a rare Mendelian disorder characterized by global developmental delay, intellectual disability, and autism. It caused truncating mutations in ADNP, which involved chromatin regulation. We hypothesized that the disruption of regulation might result specific DNA methylation patterns could be used molecular diagnosis syndrome. identified two distinct partially opposing genomic episignatures peripheral blood samples from 22 patients with The "epi-ADNP-1" episignature included ~...
Epigenetic clocks are mathematical models that predict the biological age of an individual using DNA methylation data and have emerged in last few years as most accurate biomarkers aging process. However, little is known about molecular mechanisms control rate such clocks. Here, we examined human epigenetic clock patients with a variety developmental disorders, harboring mutations proteins machinery.Using Horvath clock, perform unbiased screen for acceleration blood these patients. We...
An expanding range of genetic syndromes are characterized by genome-wide disruptions in DNA methylation profiles referred to as episignatures. Episignatures distinct, highly sensitive, and specific biomarkers that have recently been applied clinical diagnosis syndromes. contained within the broader disorder-specific changes, which can share significant overlap among different conditions. In this study, we performed functional genomic assessment comparison overlapping changes related 65 with...
Background The field of oncology is at the forefront advances in artificial intelligence (AI) health care, providing an opportunity to examine early integration these technologies clinical research and patient care. Hope that AI will revolutionize care delivery improve outcomes has been accompanied by concerns about impact on equity. Objective We aimed conduct a scoping review literature address question, “What are current potential impacts equity oncology?” Methods Following PRISMA-ScR...
Background . Thrombocytosis is a common reason for referral to Hematology. Differentiating between secondary causes of thrombocytosis and essential thrombocythemia (ET) often clinically challenging. A practical diagnostic approach identify could reduce overinvestigation such as next generation sequencing (NGS) panel. Methods Results All adult patients with (≥450 × 10 9 /L) who underwent molecular testing at single tertiary care centre January 1, 2018 May 31, 2021 were evaluated. Clinical...
Background Promoter and 5′ end methylation regulation of tumour suppressor genes is a common feature many cancers. Such occurrences often lead to the silencing these key thus they may contribute development cancer, including prostate cancer. Methodology/Principal Findings In order identify changes in we performed genome-wide analysis DNA using Agilent human CpG island arrays. Using computational gene-specific validation approaches have identified large number potential epigenetic biomarkers...
DNA methylation is an essential epigenetic mark, controlled by methyltransferase (DNMT) proteins, which regulates chromatin structure and gene expression throughout the genome. In this study, we describe a family with adult-onset autosomal dominant cerebellar ataxia deafness narcolepsy (ADCA-DN) caused mutations in maintenance DNMT1 assess profile of these individuals.We report six individuals affected ADCA-DN; specifically, patients first developed hearing loss ataxia, followed narcolepsy,...