A5075552605- Neonatal Respiratory Health Research
- Congenital Diaphragmatic Hernia Studies
- Respiratory Support and Mechanisms
- Pregnancy and preeclampsia studies
- Neuroscience of respiration and sleep
- Hedgehog Signaling Pathway Studies
- Neonatal Health and Biochemistry
- Chromatin Remodeling and Cancer
- Birth, Development, and Health
- Cardiac Arrest and Resuscitation
- Tissue Engineering and Regenerative Medicine
- Cancer, Hypoxia, and Metabolism
- Fibroblast Growth Factor Research
- Renal and related cancers
- Pulmonary Hypertension Research and Treatments
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- Congenital heart defects research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Proteoglycans and glycosaminoglycans research
- Sphingolipid Metabolism and Signaling
- Congenital Anomalies and Fetal Surgery
- Erythrocyte Function and Pathophysiology
- Ethics and Legal Issues in Pediatric Healthcare
- Glioma Diagnosis and Treatment
Hospital for Sick Children
2016-2025
University of Toronto
2016-2025
Lund University
2024
Centre for Global Health Research
2024
Muscular Dystrophy Canada
2023
SickKids Foundation
2012-2022
Institute of Medical Sciences
2015-2022
Czech Academy of Sciences, Institute of Physiology
1999-2021
John Radcliffe Hospital
2020
Wellcome Centre for Integrative Neuroimaging
2020
During early pregnancy, placentation occurs in a relatively hypoxic environment that is essential for appropriate embryonic development. Intervillous blood flow increases around 10 to 12 weeks of gestation and results exposure trophoblast cells increased oxygen tension. Before this time, low appears prevent differentiation toward an invasive phenotype. Using human villous explants 5–8 weeks’ gestation, we found tension triggered proliferation, fibronectin synthesis, α5 integrin expression,...
Abstract Background: Oxygen plays a central role in human placental pathologies including preeclampsia, leading cause of fetal and maternal death morbidity. Insufficient uteroplacental oxygenation preeclampsia is believed to be responsible for the molecular events clinical manifestations this disease. Design: Using high-throughput functional genomics, we determined global gene expression profiles placentae from high altitude pregnancies, natural vivo model chronic hypoxia, as well that...
As the lipidomics field continues to advance, self-evaluation within community is critical. Here, we performed an interlaboratory comparison exercise for using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The study comprised 31 diverse laboratories, with each laboratory different workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates associated uncertainties...
Preeclampsia, the major cause of maternal morbidity and mortality in developed countries, is associated with abnormalities placenta function due to shallow invasion decidua by trophoblasts. Data suggest that TGF-beta may play a role inhibiting trophoblast outgrowth or invasion, both. We report placental 3 expression high early pregnancy but falls at around 9 weeks' gestation. This pattern inversely correlated fibronectin synthesis, markers differentiation toward an invasive phenotype....
Abstract Epithelial-mesenchymal interactions are required for the development of all solid organs but few molecular mechanisms that underlie these have been identified. Pod1 is a basic-helix-loop-helix (bHLH) transcription factor highly expressed in mesenchyme developing include lung, kidney, gut and heart glomerular visceral epithelial cells (podocytes). To determine function vivo, we generated lacZ-expressing null allele. Null mutant mice born die perinatal period with severely hypoplastic...
To test the hypothesis that induction of heat shock proteins before onset sepsis could prevent or reduce organ injury and death in a rat model intra-abdominal sepsis-induced acute lung produced by cecal ligation perforation.Prospective, blind, randomized, controlled trial.University research laboratory.One-hundred forty-two adult Sprague-Dawley rats (weight range 200 to 300 g).Production exposure stress. Animals were randomly divided into four groups: heated septic, sham-septic, unheated...
Permissive hypercapnia, involving tolerance to elevated PaCO2 , is associated with reduced acute lung injury (ALI), thought result from mechanical stretch, and improved outcome in ARDS. However, deliberately elevating inspired CO2 concentration alone (therapeutic TH) protects against ALI ex vivo models. We investigated whether TH would protect an model of ischemia–reperfusion (IR). Anesthetized open chest rabbits were ventilated (standard eucapnic settings), randomized (Fi 0.12) versus...
Gastro-esophageal reflux and related pulmonary bile acid aspiration were prospectively investigated as possible contributors to postlung transplant bronchiolitis obliterans syndrome (BOS). We also studied the impact of on surfactant collectin proteins SP-A SP-D phospholipids--all important components innate immunity in lung. Proximal distal esophageal 24-h pH testing broncho-alveolar lavage fluid (BALF) assays performed at 3-month posttransplant 50 patients. BALF was assayed for SP-A,...
Bioactive sphingolipids including ceramides are involved in a variety of pathophysiological processes by regulating cell death and survival. The objective the current study was to examine ceramide metabolism preeclampsia, serious disorder pregnancy characterized oxidative stress, increased trophoblast autophagy. Maternal circulating placental levels quantified tandem mass spectrometry were elevated pregnancies complicated preeclampsia. Placental due greater de novo synthesis via high serine...
Abstract Despite being critical for normal brain function, the pools that supply docosahexaenoic acid (DHA) to are not agreed upon. Using multiple kinetic models in free-living adult rats, we first demonstrate DHA uptake from plasma non-esterified fatty (NEFA) pool predicts of upon oral administration, which enters NEFA as well esterified pools. The rate loss by is similar pool. Furthermore, acute iv although more radiolabeled lysophosphatidylcholine (LPC)-DHA than NEFA-DHA, this due longer...
Mechanical ventilation can injure the lung and induce a proinflammatory state; such ventilator-induced injury (VILI) is associated with neutrophil influx. Neutrophils release DNA granular proteins as cytotoxic extracellular traps (NETs). The authors hypothesized that NETs were produced in VILI model may contribute to injury.In two-hit lipopolysaccharide/VILI mouse without intratracheal deoxyribonuclease (DNase) treatment or blockade of known inducers NET formation (NETosis), assessed...
Abstract Mitochondria are in a constant balance of fusing and dividing response to cellular cues. Fusion creates healthy mitochondria, whereas fission results removal non-functional organelles. Changes mitochondrial dynamics typify several human diseases. However, the contribution preeclampsia, hypertensive disorder pregnancy characterized by placental cell autophagy death, remains unknown. Herein, we show that dynamic preeclamptic placentae is tilted toward (increased DRP1...
Rationale: The physiological basis of lung protection and the impact positive end-expiratory pressure (PEEP) during pronation in acute respiratory distress syndrome are not fully elucidated. Objectives: To compare pleural (Ppl) gradient, ventilation distribution, regional compliance between dependent nondependent lungs, investigate effect PEEP supination pronation. Methods: We used a two-hit model injury (saline lavage high-volume ventilation) 14 mechanically ventilated pigs studied supine...
Rationale: It is unknown whether preventing overdistention or collapse more important when titrating positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS). Objective: To compare PEEP targeting either minimal overdistention, using a compromise between and randomized trial, assess the impact on mechanics, gas exchange, inflammation, hemodynamics. Methods: In porcine model of ARDS, lung were estimated by electrical impedance tomography during decremental...
BACKGROUND: Iron is an essential micronutrient for cell survival and growth; however, excess of this metal drives ferroptosis. Although maternal iron imbalance placental hypoxia are independent contributors to the pathogenesis preeclampsia, a hypertensive disorder pregnancy, mechanisms by which their interaction impinge on health remain elusive. METHODS: We used placentae from normotensive preeclampsia pregnancy cohorts, human H9 embryonic stem cells differentiated into cytotrophoblast-like...
On the basis of in vivo animal studies and on experiments nature, it has been suggested that fetal breathing movements are essential for normal lung growth utero. To study this hypothesis vitro, we examined effect mechanical stretch proliferation rat cells maintained organotypic culture to provide a three-dimensional matrix. Initial demonstrated stretch-mediated effects cell division DNA synthesis such cultures were influenced by inoculation density, calf serum concentration, amplitude,...
Recent investigations have suggested an active role for endothelial cells in organ development, including the lung. Herein, we investigated some of molecular mechanisms underlying normal pulmonary vascular development and their influence on epithelial branching morphogenesis. Because lung utero develops a relative hypoxic environment, first low oxygen Two transgenic mouse models, C101-LacZ (epithelial-LacZ marker) Tie2-LacZ (endothelial-LacZ marker), were used. At embryonic day 11.5,...
The purpose of this study was to use gene expression profiling understand how adult rat lung responds high tidal volume (HV) ventilation in vivo. HV for 30 minutes did not cause discernable injury (in terms altered mechanics or histology) but caused obvious when continued 90 minutes. However, at 30-minute ventilation, significant upregulation 10 genes and suppression 12 genes. Among the upregulated were transcription factors, stress proteins, inflammatory mediators; downregulated exemplified...
Physical forces play important roles in regulating cell proliferation, differentiation, and death by activating intracellular signal transduction pathways. How cells sense mechanical stimulation, however, is largely unknown. Most studies focus on cellular membrane proteins such as ion channels, integrins, receptors for growth factors mechanosensory units. Here we show that stretch-induced c-Src protein tyrosine kinase activation mediated through the actin filament-associated (AFAP)....