A5084026631- Pluripotent Stem Cells Research
- Animal Genetics and Reproduction
- Gene expression and cancer classification
- RNA modifications and cancer
- Bioinformatics and Genomic Networks
- Nuclear Receptors and Signaling
- Epigenetics and DNA Methylation
- Reproductive System and Pregnancy
- Extracellular vesicles in disease
- Cancer-related molecular mechanisms research
- Adipose Tissue and Metabolism
- Single-cell and spatial transcriptomics
- Hypothalamic control of reproductive hormones
- Birth, Development, and Health
- Renal and related cancers
- Physiological and biochemical adaptations
- interferon and immune responses
- Prenatal Substance Exposure Effects
- Mitochondrial Function and Pathology
- Maternal Mental Health During Pregnancy and Postpartum
- Congenital heart defects research
- Chromatin Remodeling and Cancer
- Animal Behavior and Reproduction
- Growth Hormone and Insulin-like Growth Factors
- Legal and Policy Issues
University of Toronto
2019-2025
Hospital for Sick Children
2019-2025
SickKids Foundation
2020-2024
Ontario Institute for Cancer Research
2024
New York Academy of Sciences
2023
John Wiley & Sons (Germany)
2023
Moss Landing Marine Laboratories
2023
Hudson Institute
2023
Great Ormond Street Hospital
2022
University College London
2022
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...
Abstract Low blood flow through the fetal left heart is often conjectured as an etiology for hypoplastic syndrome (HLHS). To investigate if a decrease in results growth failure, we generate ventricular inflow obstruction (LVIO) mid-gestation lambs by implanting coils their atrium using ultrasound-guided percutaneous technique. Significant LVIO recapitulates important clinical features of HLHS: decreased antegrade aortic valve flow, compensatory retrograde perfusion brain and ascending aorta...
Many regulatory factors impact the expression of individual genes including, but not limited, to microRNA, long non-coding RNA (lncRNA), transcription (TFs), cis-methylation, copy number variation (CNV), and single-nucleotide polymorphisms (SNPs). While each mechanism can influence gene substantially, relative importance at level tissues is poorly understood. Here, we present integrative Models Estimated (iModEst), which details contribution different regulators 16,000 21 within The Cancer...
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...
Inactivating mutations in SMARCB1 confer an oncogenic dependency on EZH2 atypical teratoid rhabdoid tumors (ATRTs), but the underlying mechanism has not been fully elucidated. We found that sensitivity of ATRTs to inhibition (EZH2i) is associated with viral mimicry response. Unlike other epigenetic therapies targeting transcriptional repressors, EZH2i-induced triggered by cryptic transcription endogenous retroelements, rather mediated increased expression genes enriched for intronic...
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...
Abstract The usability of publicly-available gene expression data is often limited by the availability high-quality, standardized biological phenotype and experimental condition information (“metadata”). We released recount2 project, which involved re-processing ∼70,000 samples in Sequencing Read Archive (SRA), Genotype-Tissue Expression (GTEx), Cancer Genome Atlas (TCGA) projects. While from latter two projects are well-characterized with extensive metadata, ∼50,000 RNA-seq SRA...
Mouse models of fetal alcohol spectrum disorders (FASD) have repeatedly identified genes with long-term changes in expression, DNA methylation, noncoding RNA, and histone modifications response to neurodevelopmental exposure. Articulation FASD is achieved via alcohol's effect on gene likely involving epigenetic regulation. The list affected large heterogeneous, depending experimental protocol. We present reanalysis synthesis results highlighting the Wnt transcription factor 7 like 2 (Tcf7l2)...
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...
Genes are often pleiotropic and plastic in their expression, features which increase diversify the functionality of genome. The foraging (for) gene Drosophila melanogaster is highly a long-standing model for studying individual differences behavior plasticity from ethological, evolutionary, genetic perspectives. Its pleiotropy known to be linked its complex molecular structure; however, downstream pathways interactors remain mostly elusive. To uncover these gain better understanding how...
Abstract Although the hypothalamus plays a critical role in regulation of puberty, more research is needed to identify gene regulatory networks that control pubertal timing. Here, we investigate age-, sex- and cell-type-specific across transition. We used RNA-seq profile hypothalamic expression male female mice at five time points spanning onset puberty (postnatal days (PD) 12, 22, 27, 32, 37). By combining this data with scRNA-seq pre- post-pubertal mice, were able assign changes their cell...
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...
ABSTRACT 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...
I am often asked how our mother inspired my sister Moriah and me to want become scientists. She never directly suggested we should go down that path. Instead, she shared the aspects of natural world, loved, with us while keeping non-science her job separate from lives at home. Now, have learned perspective provides insights spark innovative discoveries, some which challenged status quo. Her passion for research has allowed pursue what believes be worth studying. personality collaborative...
Abstract The pituitary gland is integral to the regulation of growth, metabolism, puberty, reproduction, and stress responses. Previously, we found that many genes associated with age-at-menarche in genome-wide association studies (GWAS) displayed increasingly sex-biased expression across pubertal transition mouse pituitary. However, whether this trend exists beyond puberty-related was not known. In addition, regulatory mechanisms underlying these gene changes remained be explored. To answer...
ABSTRACT 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...