A5009231300- Respiratory Support and Mechanisms
- Caveolin-1 and cellular processes
- Cell Adhesion Molecules Research
- Sepsis Diagnosis and Treatment
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Erythrocyte Function and Pathophysiology
- Atherosclerosis and Cardiovascular Diseases
- Blood properties and coagulation
- Neonatal Respiratory Health Research
- Extracellular vesicles in disease
- Ultrasound and Hyperthermia Applications
- Influenza Virus Research Studies
- Cardiac Arrest and Resuscitation
- S100 Proteins and Annexins
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Cancer, Lipids, and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Immune Response and Inflammation
- Pancreatic function and diabetes
- Lipid metabolism and disorders
- Intensive Care Unit Cognitive Disorders
- Ultrasound and Cavitation Phenomena
- Complement system in diseases
- Renal and Vascular Pathologies
- Neuroscience of respiration and sleep
University of Toronto
2016-2025
St. Michael's Hospital
2016-2025
Institute for Biomedical Engineering
2025
Toronto Metropolitan University
2017-2024
Unity Health Toronto
2020-2024
Centre of Biomedical Research
2020-2022
Ten Chen Hospital
2016
Lee University
2016
Hospital for Sick Children
2003-2015
SickKids Foundation
2003-2015
Molecular dissection in three models of sepsis implicates a signaling pathway maintaining adhesion endothelial cells to protect against vascular leak.
Recent data indicate that disruption of the microvascular endothelial barrier is a key determinant pathogenesis sepsis.
Virulence of Mycobacterium tuberculosis and related pathogenic mycobacteria requires the secretion early secretory antigenic 6 kDa (ESAT-6) culture filtrate protein 10 (CFP-10), two small proteins that lack traditional signal sequences are exported through an alternative pathway encoded primarily by RD1 genetic locus. Mutations affecting synthesis or ESAT-6 CFP-10 attenuate virulence M. in murine models infection. However, specific functions these their system currently unclear. In this...
Retention of low-density lipoprotein (LDL) cholesterol beneath the arterial endothelium initiates an inflammatory response culminating in atherosclerosis. Since overlying is healthy and intact early on, it likely that LDL passes through endothelial cells by transcytosis. However, technical challenges have made confirming this notion elucidating mechanisms transcytosis difficult. We developed a novel assay for measuring real time across coronary cell monolayers; we used approach to identify...
Abstract In humans and animals lacking functional LDL receptor (LDLR), from plasma still readily traverses the endothelium. To identify pathways of uptake, a genome-wide RNAi screen was performed in endothelial cells cross-referenced with GWAS-data sets. Here we show that activin-like kinase 1 (ALK1) mediates uptake into cells. ALK1 binds lower affinity than LDLR saturates only at hypercholesterolemic concentrations. via an unusual endocytic pathway diverts ligand lysosomal degradation...
Atherosclerosis is driven by synergistic interactions between pathological, biomechanical, inflammatory, and lipid metabolic factors. Our previous studies demonstrated that absence of caveolin-1 (Cav1)/caveolae in hyperlipidemic mice strongly inhibits atherosclerosis, which was attributed to activation endothelial nitric oxide (NO) synthase (eNOS) increased production NO reduced inflammation low-density lipoprotein trafficking. However, the contribution eNOS athero-protection Cav1 exact...
Deficiency of lncRNA SNHG12 impairs DNA damage repair in the vessel wall and predisposes to vascular senescence atherosclerosis.
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Severe influenza infections are complicated by acute lung injury, a syndrome of pulmonary microvascular leak. The pathogenesis this complication is unclear. We hypothesized that human could directly infect the endothelium, leading to loss endothelial barrier function. infected endothelium with both clinical and laboratory strains influenza. Permeability monolayers was assessed spectrofluorimetry measurement transendothelial electrical resistance. determined molecular mechanisms flu-induced...
The vascular endothelium supplying the brain exhibits very low paracellular and transcellular permeability is a major constituent of blood-brain barrier. High-density lipoprotein (HDL) crosses barrier by transcytosis, but technical limitations have made it difficult to elucidate its regulation. Using combination spinning-disc confocal total internal reflection fluorescence microscopy, we examined uptake transcytosis HDL human primary microvascular endothelial cell monolayers. these...
Extracellular vesicles (EVs) contain bioactive cargo including miRNAs and proteins that are released by cells during cell-cell communication. Endothelial (ECs) form the innermost lining of all blood vessels, interfacing with in circulation vascular wall. It is unknown whether ECs release EVs capable governing recipient within these 2 separate compartments. Given their boundary location, we propose use bidirectional distinct EV quiescent (healthy) activated (atheroprone) states to communicate vessel
Hemolytic uremic syndrome (HUS) is a potentially life-threatening condition. It often occurs after gastrointestinal infection with E. coli O157:H7, which produces Shiga toxins (Stx) that cause hemolytic anemia, thrombocytopenia, and renal injury. Stx-mediated changes in endothelial phenotype have been linked to the pathogenesis of HUS. Here we report our studies investigating Stx-induced gene expression their contribution Stx function by inactivating host ribosomes but can also alter at...
Transport of insulin across the microvasculature is necessary to reach its target organs (e.g., adipose and muscle tissues) rate limiting in action. Morphological evidence suggests that enters endothelial cells microvasculature, studies with large vessel-derived show uptake; however, little known about actual transcytosis how this occurs relevant microvascular cells. We report an approach study individual, primary human (HAMECs), involving uptake followed by vesicle-mediated exocytosis...
Objective- The atheroprotective effects of estrogen are independent circulating lipid levels. Whether regulates transcytosis LDL (low-density lipoprotein) across the coronary endothelium is unknown. Approach and Results- Using total internal reflection fluorescence microscopy, we quantified human artery endothelial cells from multiple donors. was significantly higher in men compared with premenopausal women. Estrogen attenuated by male but not female donors; albumin affected. caused...
Obesity is associated with inflammation and immune cell recruitment to adipose tissue, muscle intima of atherosclerotic blood vessels. hyperlipidemia are also tissue insulin resistance can compromise delivery muscle. The muscle/fat microvascular endothelium mediates facilitates monocyte transmigration, yet its contribution the consequences poorly understood. Using primary endothelial cells from human microvasculature (HAMEC), we investigated effects physiological levels fatty acids on...