A5011265113- Pulmonary Hypertension Research and Treatments
- Inflammasome and immune disorders
- Respiratory Support and Mechanisms
- Cellular transport and secretion
- Neuroscience of respiration and sleep
- Advanced Glycation End Products research
- Cell death mechanisms and regulation
- Cardiac, Anesthesia and Surgical Outcomes
- Biomedical Research and Pathophysiology
- Neonatal Respiratory Health Research
- Heme Oxygenase-1 and Carbon Monoxide
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Eicosanoids and Hypertension Pharmacology
- RNA and protein synthesis mechanisms
- COVID-19 and healthcare impacts
- Calcium signaling and nucleotide metabolism
- Lipid Membrane Structure and Behavior
- Congenital Heart Disease Studies
- Macrophage Migration Inhibitory Factor
- Intensive Care Unit Cognitive Disorders
- Nosocomial Infections in ICU
- Cardiac Arrhythmias and Treatments
- Erythrocyte Function and Pathophysiology
- Airway Management and Intubation Techniques
- Health and Medical Research Impacts
University of Toronto
2014-2025
Hospital for Sick Children
2015-2025
SickKids Foundation
2015-2024
Great Ormond Street Hospital
2022-2024
University College London
2022-2024
Canada Research Chairs
2009-2023
Committee on Publication Ethics
2019
St. Michael's Hospital
2011-2018
Lee University
2016
Ten Chen Hospital
2016
Recent data indicate that disruption of the microvascular endothelial barrier is a key determinant pathogenesis sepsis.
The protein high-mobility group box 1 (HMGB1) is released into the extracellular space in response to many inflammatory stimuli, where it a potent signaling molecule. Although research has focused on downstream HMGB1 signaling, means by which exits cell controversial. Here we demonstrate that not from bone marrow-derived macrophages (BMDM) after lipopolysaccharide (LPS) treatment. We also explore whether via pore-forming gasdermin D inflammasome activation, as case for IL-1β. only under...
Abstract Plasma membrane rupture (PMR) in dying cells undergoing pyroptosis or apoptosis requires the cell-surface protein NINJ1 1 . PMR releases pro-inflammatory cytoplasmic molecules, collectively called damage-associated molecular patterns (DAMPs), that activate immune cells. Therefore, inhibiting and may limit inflammation is associated with excessive cell death. Here we describe an anti-NINJ1 monoclonal antibody specifically targets mouse blocks oligomerization of NINJ1, preventing PMR....
First recognized more than 30 years ago, glycine protects cells against rupture from diverse types of injury. This robust and widely observed effect has been speculated to target a late downstream process common multiple modes tissue The molecular that mediates cytoprotection, however, remains elusive. Here, we show works at the level NINJ1, newly identified executioner plasma membrane in pyroptosis, necrosis, post-apoptosis lysis. NINJ1 is thought cluster within cause cell rupture. We...
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Inflammasomes are multiprotein complexes tasked with sensing endogenous or exogenous inflammatory signals and integrating this signal into a downstream response. Inflammasome activation has been implicated in variety of pulmonary diseases, including hypertension, bacterial pneumonia, COPD, asthma. Of increasing interest is the contribution inflammasome context acute lung injury/acute respiratory distress syndrome (ALI/ARDS). both parenchyma resident immune cells generates intereukin-1β...
Significance Hypoxic pulmonary vasoconstriction (HPV) is a physiological mechanism that protects against systemic hypoxemia by redistributing blood flow from poorly to better ventilated areas of the lung, thereby minimizing ventilation-perfusion mismatch. However, in chronic hypoxemia-associated lung disease, HPV contributes hypertension. In this study, we provide novel evidence for dual role sphingolipids as important signal mediators HPV, which critically depends on presence functional...
Over past years, a critical role for the immune system and, in particular, mast cells pathogenesis of pulmonary hypertension (PH) has emerged. However, way which promote PH is still poorly understood. Here, we investigated mechanisms by may contribute to PH, specifically focusing on interaction between innate and adaptive response B autoimmunity. Experiments were performed Sprague-Dawley rats cell-deficient JH-KO monocrotaline, Sugen/hypoxia, aortic banding model PH. Hemodynamics, cell...
Hypoxic pulmonary vasoconstriction (HPV) is critically important in regionally heterogeneous lung diseases by directing blood toward better-oxygenated units, yet the molecular mechanism of HPV remains unknown. Transient receptor potential (TRP) channels are a large cation channel family that has been implicated HPV, specifically artery smooth muscle cell (PASMC) Ca and contractile response to hypoxia. In this study, authors probed role TRP member, TRPV4, HPV.HPV was assessed using isolated...
LDL (low-density lipoprotein) transcytosis across the endothelium is performed by SR-BI (scavenger receptor class B type 1) and contributes to atherosclerosis. HMGB1 (high mobility group box a structural protein in nucleus that released cells during inflammation; extracellular has been implicated advanced disease. Whether intracellular regulates through its nuclear functions unknown. Approach Results: was depleted siRNA human coronary artery endothelial cells, of measured total internal...
Golgi-localized Rab34 has been implicated in repositioning lysosomes and activation of macropinocytosis. Using HeLa cells, we undertook a detailed investigation involvement intracellular vesicle transport. Immunoelectron microscopy immunocytochemistry confirmed that is localized to the Golgi stack active shifts cell center. Contrary previous report, found not concentrated at membrane ruffles involved fluid-phase uptake. Also, Rab34-induced does affect mannose 6-phosphate receptor...
Abstract Recent data suggest that adopting a lung protective ventilation strategy will benefit healthy surgical patients. The authors examine the data, and exercising caution prior to implementing practice change affect massive population.
The Cre-Lox system is essential in biomedical research for precise gene deletion specific cell types, crucial understanding genetic roles disease. Although generally considered non-detrimental, Cre recombinase expression has been associated with potential adverse effects, including toxicity, ectopic expression, and disruption of endogenous genes. We investigated the role macrophage nucleotide-binding oligomerization domain (Nod1) obesity-associated diabetes using myeloid-specific...