A5005982193- Animal Genetics and Reproduction
- Pluripotent Stem Cells Research
- RNA Research and Splicing
- RNA modifications and cancer
- Reproductive System and Pregnancy
- Cancer therapeutics and mechanisms
- Genomics and Chromatin Dynamics
- Gene expression and cancer classification
- Bioinformatics and Genomic Networks
- Neonatal Respiratory Health Research
- Epigenetics and DNA Methylation
- Adipose Tissue and Metabolism
- Cancer Genomics and Diagnostics
- Cardiovascular Disease and Adiposity
- Hypothalamic control of reproductive hormones
- Genomics and Rare Diseases
- Ubiquitin and proteasome pathways
- Renal and related cancers
- Nuclear Receptors and Signaling
- 14-3-3 protein interactions
- COVID-19 Clinical Research Studies
- Hedgehog Signaling Pathway Studies
- Growth Hormone and Insulin-like Growth Factors
- Molecular Biology Techniques and Applications
- interferon and immune responses
Hospital for Sick Children
2016-2025
SickKids Foundation
2016-2024
Great Ormond Street Hospital
2022-2024
University College London
2022-2024
University of Toronto
2012-2021
Canada Research Chairs
2012
Type II DNA topoisomerases (TOP2) regulate topology by generating transient double stranded breaks during replication and transcription. Topoisomerase beta (TOP2B) facilitates rapid gene expression functions at the later stages of development differentiation. To gain new insight into genome biology TOP2B, we used proteomics (BioID), chromatin immunoprecipitation, high-throughput chromosome conformation capture (Hi-C) to identify novel proximal TOP2B protein interactions characterize genomic...
Administration of extracellular vesicles derived from amniotic fluid stem cells regenerates underdeveloped fetal lungs in rodents.
Leiomyosarcomas (LMS) are genetically heterogeneous tumors differentiating along smooth muscle lines. Currently, LMS treatment is not informed by molecular subtyping and associated with highly variable survival. While disease site continues to dictate clinical management, the contribution of genetic factors subtype, origins, timing unknown. Here we analyze 70 genomes 130 transcriptomes LMS, including multiple tumor regions paired metastases. Molecular profiling highlight very early origins...
During the maternal-to-zygotic transition (MZT) vast changes in embryonic transcriptome are produced by a combination of two processes: elimination maternally provided mRNAs and synthesis new transcripts from zygotic genome. Previous genome-wide analyses MZT have been restricted to whole embryos. Here we report first such analysis for primordial germ cells (PGCs), progenitors germ-line stem cells.We purified PGCs Drosophila embryos, defined their proteome transcriptome, assessed content,...
Endothelial cell (EC) activation, endotheliitis, vascular permeability, and thrombosis have been observed in patients with severe coronavirus disease 2019 (COVID-19), indicating that the vasculature is affected during acute stages of SARS-CoV-2 infection. It remains unknown whether circulating markers are sufficient to predict clinical outcomes, unique COVID-19, if permeability can be therapeutically targeted.Prospectively evaluating prevalence inflammatory, cardiac, EC activation as well...
Genome sequencing (GS) is a powerful test for the diagnosis of rare genetic disorders. Although GS can enumerate most non-coding variation, determining which variants are disease-causing challenging. RNA (RNA-seq) has emerged as an important tool to help address this issue, but its diagnostic utility remains understudied, and added value trio design unknown. We performed plus RNA-seq from blood using automated clinical-grade high-throughput platform on 97 individuals 39 families where...
The timing of human puberty is highly variable, sexually dimorphic, and associated with adverse health outcomes. Over 20 genes carrying rare mutations have been identified in known pubertal disorders, many which encode critical components the hypothalamic-pituitary-gonadal (HPG) axis. Recent genome-wide association studies (GWAS) more than 100 candidate at loci age menarche or voice breaking males. We know little about spatial, temporal postnatal expression patterns majority these...
Abstract RNA sequencing (RNA-seq) is widely used to identify differentially expressed genes (DEGs) and reveal biological mechanisms underlying complex processes. RNA-seq often performed on heterogeneous samples the resulting DEGs do not necessarily indicate cell-types where differential expression occurred. While single-cell (scRNA-seq) methods solve this problem, technical cost constraints currently limit its widespread use. Here we present single cell Mapper (scMappR), a method that...
Canonical splice site variants (CSSVs) are often presumed to cause loss-of-function (LoF) and assigned very strong evidence of pathogenicity (according American College Medical Genetics/Association for Molecular Pathology criterion PVS1). The exact nature predictability splicing effects unselected rare CSSVs in blood-expressed genes poorly understood. We identified 168 112 individuals using genome sequencing, studied their impact on RNA sequencing (RNA-seq). There was no a frameshift, nor...
Abstract Type-II topoisomerases resolve topological stress in DNA through controlled double-strand breaks. While TOP2A is a chemotherapy target proliferating cells, the ubiquitously expressed TOP2B potential off-target. Here we explore roles of mutagenesis by generating DNA-binding maps TOP2B, CTCF, and RAD21 human cancer samples analyzing these for driver mutations mutational processes 6500 whole genomes. TOP2B-CTCF-RAD21 TOP2B-RAD21 sites are enriched somatic structural variants (SVs),...
During gestation, uterine smooth muscle cells transition from a state of quiescence to one contractility, but the molecular mechanisms underlying this at genomic level are not well-known. To better understand these events, we evaluated epigenetic landscape mouse myometrium during pregnant, laboring, and postpartum stages. We generated gestational time point–specific enrichment profiles for histone H3 acetylation on lysine residue 27 (H3K27ac), trimethylation 4 (H3K4me3), RNA polymerase II...
The pituitary gland regulates essential physiological processes such as growth, pubertal onset, stress response, metabolism, reproduction, and lactation. While sex biases in these functions hormone production have been described, the underlying identity, temporal deployment, cell-type specificity of sex-biased gene regulatory networks are not fully understood.To capture differences regulation dynamics during postnatal development, we performed 3' untranslated region sequencing small RNA to...
Differential gene expression analysis using RNA sequencing (RNA-seq) data is a standard approach for making biological discoveries. Ongoing large-scale efforts to process and normalize publicly available enable rapid systematic reanalysis. While several powerful tools systematically RNA-seq data, enabling their reanalysis, few resources recompute differentially expressed genes (DEGs) generated from individual studies. We developed robust differential pipeline 3162 human DEG lists The Cancer...
Shortening ends of mRNAs cooperate with oncogenes in development and cancer.
Abstract RNA sequencing (RNA-seq) is widely used to identify differentially expressed genes (DEGs) and reveal biological mechanisms underlying complex processes. RNA-seq often performed on heterogeneous samples the resulting DEGs do not necessarily indicate cell types where differential expression occurred. While single-cell (scRNA-seq) methods solve this problem, technical cost constraints currently limit its widespread use. Here we present single Mapper (scMappR), a method that assigns...
ABSTRACT Type-II topoisomerases resolve topological stress in DNA through controlled double-strand breaks. While TOP2A is a chemotherapy target proliferating cells, the ubiquitously expressed TOP2B potential off-target. Here we explore roles of mutagenesis by generating DNA-binding maps TOP2B, CTCF, and RAD21 human cancer samples analysing these for driver mutations mutational processes 6500 whole genomes. TOP2B-CTCF-RAD21 TOP2B-RAD21 sites are enriched somatic structural variants (SVs),...
The naked mole-rat (NMR; Heterocephalus glaber ) is a eusocial subterranean rodent with highly unusual set of physiological traits that has attracted great interest amongst the scientific community. However, genetic basis most these not been elucidated. To facilitate our understanding molecular mechanisms underlying NMR physiology and behaviour, we generated long-read chromosomal-level genome assembly NMR. This was subsequently annotated incorporated into multiple whole alignments in Ensembl...