A5101548895- Muscle Physiology and Disorders
- Infant Nutrition and Health
- Congenital heart defects research
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Birth, Development, and Health
- Pregnancy and preeclampsia studies
- Fungal and yeast genetics research
- RNA Research and Splicing
- Tissue Engineering and Regenerative Medicine
- Neonatal Respiratory Health Research
- Mitochondrial Function and Pathology
- Clinical Nutrition and Gastroenterology
- Pediatric Hepatobiliary Diseases and Treatments
- Genomics and Chromatin Dynamics
- Plant Reproductive Biology
- Cardiomyopathy and Myosin Studies
- Digestive system and related health
- Yeasts and Rust Fungi Studies
- Aldose Reductase and Taurine
- Prenatal Screening and Diagnostics
- Adipose Tissue and Metabolism
- Plant Gene Expression Analysis
- Genetics, Aging, and Longevity in Model Organisms
- Viral Infections and Immunology Research
Hospital for Sick Children
1997-2024
University of Toronto
1997-2023
SickKids Foundation
2018
Initial pollen-pistil interactions in the Brassicaceae are regulated by rapid communication between pollen grains and stigmatic papillae fundamentally important, as they first step toward successful fertilization. The goal of this study was to examine requirement exocyst subunits, which function docking secretory vesicles sites polarized secretion, context interactions. One subunit genes, EXO70A1, previously identified an essential factor stigma for acceptance compatible Arabidopsis...
Major risk factors for necrotizing enterocolitis (NEC) are formula feeding and prematurity, however, their pathogenic mechanisms unknown. We found that insufficient arginine/nitric oxide synthesis limits blood flow in the intestinal microvasculature, leading to hypoxia, mucosa damage NEC premature intestine after feeding. Formula led increased hypoxia pups at postnatal day 1(P1) P5, but not more mature P9. Accordingly, microvasculature only P9 pups. mRNA profiling revealed regulators of...
The existence of histone H1 in the yeast, Saccharomyces cerevisiae, has long been debated. In this report we describe presence yeast. YPL127c, a gene encoding protein with high degree similarity to from other species was sequenced as part contribution Montreal Yeast Genome Sequencing Group chromosome XVI. To reflect similarity, designation changed HHO1 (Histone H One). is highly expressed poly A+ RNA Although deletion had no detectable effect on cell growth, viability or mating, it...
Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency and currently the leading cause of mortality in preterm infants. Recent studies show that human milk oligosaccharides (HMOs) reduce frequency incidence NEC; however, molecular mechanisms for their protection are largely unexplored.To address this gap, genome-wide profiling intestinal epithelial transcriptome response to HMOs using RNA-sequencing performed. It found alter host 225 unique target genes pertaining cell...
ABSTRACT Duchenne muscular dystrophy (DMD) is a life-threatening neuromuscular disease caused by the lack of dystrophin, resulting in progressive muscle wasting and locomotor dysfunctions. By adulthood, almost all patients also develop cardiomyopathy, which primary cause death DMD. Although there has been extensive effort creating animal models to study treatment strategies for DMD, most fail recapitulate complete skeletal cardiac manifestations that are presented affected patients. Here, we...
Abstract Cardiac metabolism is deranged in heart failure, but underlying mechanisms remain unclear. Here, we show that lysine demethylase 8 (Kdm8) maintains an active mitochondrial gene network by repressing Tbx15 , thus preventing dilated cardiomyopathy leading to lethal failure. Deletion of Kdm8 mouse cardiomyocytes increased H3K36me2 with activation and repression target genes the NAD + pathway before initiated. supplementation prevented mutant mice, TBX15 overexpression blunted...
Defective fetoplacental vascular maturation causes intrauterine growth restriction (IUGR). A transcriptional switch initiates placental where blood vessels elongate. However, cellular mechanisms and regulatory pathways involved are unknown. We show that the histone methyltransferase Ehmt2, also known as G9a, activates Notch pathway to promote maturation. Placental vasculature from embryos with G9a-deficient endothelial progenitor cells failed expand due decreased cell proliferation increased...
The CCCTC-binding factor (CTCF) is a versatile transcriptional regulator required for embryogenesis, but its function in vascular development or diseases with component poorly understood. Here, we found that endothelial Ctcf essential mouse and limits accumulation of reactive oxygen species (ROS). Conditional knockout progenitors their descendants affected embryonic growth, caused lethality at day 10.5 because defective yolk sac placental development. Analysis global gene expression revealed...
Heart disease risk can be programmed by intrauterine exposure to obesity. Dysregulating key transcription factors in cardiac progenitors cause subsequent adult-onset heart disease. In this study, we investigated the transcriptional pathways that are altered embryonic and linked offspring exposed obesity during pregnancy. Female mice were fed an obesogenic diet mated with males a control diet. function genome-wide gene expression analyzed adult born obese lean at baseline response stress....
The neonatal mouse heart has the remarkable capacity to regenerate lost myocardium within first week of life. Neonatal cardiomyocytes re-express fetal genes that control cell proliferation after injury promote regeneration. loss regenerative one birth coincides with repression a transcriptional program coordinated by epigenetic regulators. histone methyltransferase enhancer zeste homolog 2 (Ezh2) is repressor cardiac programs and suppresses cardiomyocyte proliferation, suggesting potential...
Purpose Necrotizing enterocolitis (NEC) is one of the most distressing gastrointestinal emergencies affecting neonates. Amniotic fluid stem cells (AFSC) improve intestinal injury and survival in experimental NEC but are difficult to administer. In this study, we evaluated whether conditioned medium (CM) derived from human AFSC have protective effects. Methods Three groups C57BL/6 mice were studied: (i) breast-fed as control; (ii) receiving PBS; (iii) CM. was induced between post-natal days...
Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency affecting preterm infants. Breastmilk protects against NEC, partly due to human milk oligosaccharides (HMOs). HMO compositions are highly diverse, and it unclear if anti-NEC properties specific carbohydrate motifs. Here, this study compares intestinal epithelial transcriptomes of five synthetic HMOs (sHMOs) examines structure-function relationships on signaling.This interrogates the transcriptome Caco-2Bbe1 cells in...
Duchenne muscular dystrophy (DMD) is a disease with life-threatening trajectory resulting from mutations in the dystrophin gene, leading to degeneration of skeletal muscle and fibrosis cardiac muscle. The overwhelming majority are multiexonic deletions. We previously established dystrophic mouse model deletion exons 52–54 Dmd that develops an early-onset phenotype similar DMD patients. Here we employed CRISPR-Cas9 delivered intravenously by adeno-associated virus (AAV) vectors restore...
As the fetal heart develops, cardiomyocyte proliferation potential decreases while fatty acid oxidative capacity increases in a highly regulated transition known as cardiac maturation. Small noncoding RNAs, such microRNAs (miRNAs), contribute to establishment and control of tissue-specific transcriptional programs. However, small RNA expression dynamics genome-wide miRNA regulatory networks controlling maturation human remain poorly understood.Transcriptome profiling RNAs revealed temporal...
Becker Muscular Dystrophy (BMD) is a rare X-linked recessive neuromuscular disorder frequently caused by in-frame deletions in the DMD gene that result production of truncated, yet functional, dystrophin protein. The consequences BMD-causing on organism are difficult to predict, especially regard long-term prognosis. Here, we employed CRISPR-Cas9 generate new Dmd del52-55 mouse model deleting exons 52-55, resulting BMD-like deletion. To delineate effects this deletion, studied these mice...
Abstract Becker Muscular Dystrophy (BMD) is a rare X-linked recessive neuromuscular disorder caused by in-frame deletions in the DMD gene that result production of truncated, yet functional, dystrophin protein. BMD often considered milder form Duchenne Dystrophy, which mutations typically disruption reading frame and malfunction or loss dystrophin. The consequences BMD-causing on organism are more difficult to predict, especially regard long-term prognosis. Here, we employed CRISPR-Cas9...
ABSTRACT Recently we demonstrated the utility of a nerve-sparing mid-urethra model partial outlet obstruction (NeMO) that has high consistency and minimal mortalities, unlike traditional proximal to bladder neck. Our goal was uncover potential therapeutic targets by investigating genome wide transcriptional changes pathways altered in NeMO compare with published human data. We performed RNAseq analysed differentially upregulated downregulated genes for associated pathways, transcription...