A5029460367- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neonatal Respiratory Health Research
- Pulmonary Hypertension Research and Treatments
- Inhalation and Respiratory Drug Delivery
- Endoplasmic Reticulum Stress and Disease
- Occupational and environmental lung diseases
- Medical Imaging and Pathology Studies
- Tissue Engineering and Regenerative Medicine
- Asthma and respiratory diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Systemic Sclerosis and Related Diseases
- Pleural and Pulmonary Diseases
- Extracellular vesicles in disease
- Immune cells in cancer
- Occupational exposure and asthma
- Connective Tissue Growth Factor Research
- Respiratory viral infections research
- Autophagy in Disease and Therapy
- Microbial metabolism and enzyme function
- Virus-based gene therapy research
- Peptidase Inhibition and Analysis
- Immune Response and Inflammation
- Cannabis and Cannabinoid Research
- Cellular Mechanics and Interactions
- Liver Disease Diagnosis and Treatment
McMaster University
2016-2025
St. Joseph’s Healthcare Hamilton
2015-2024
McGill University
2024
McMaster University Medical Centre
2009-2023
Institute for Respiratory Health
2009-2023
Energy Norway
2023
St. Joseph's Hospital
2008-2022
RELX Group (United States)
2020
Hamilton Health Sciences
2013
University of Regensburg
2009
The clinical management of idiopathic pulmonary fibrosis (IPF) remains a major challenge due to lack effective drug therapy or accurate indicators for disease progression. Fibrocytes are circulating mesenchymal cell progenitors that involved in tissue repair and fibrosis.To test the hypothesis assay these cells may provide biomarker activity progression IPF.Fibrocytes were defined as positive CD45 collagen-1 by flow cytometry quantified patients with stable IPF during acute exacerbation...
Rationale: Recent findings suggesting transforming growth factor (TGF)-β1 activation by mechanical stimuli in vitro raised the question of whether this phenomenon was relevant vivo context pulmonary fibrosis.Objectives: To explore effect stress on TGF-β1 and its signaling pathway rat human fibrotic lung tissue using a novel ex model.Methods: Rat fibrosis induced transient gene expression active TGF-β1. Lungs were harvested at Day 14 or 21 submitted to various bath equipped with force...
In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, causing the disease 2019 (COVID-19) pandemic. SARS-CoV, agent responsible for 2003 SARS outbreak, utilises angiotensin-converting enzyme (ACE2) and transmembrane serine protease (TMPRSS2) host molecules viral entry. ACE2 TMPRSS2 have recently been implicated in SARS-CoV-2 infection. Additional including ADAM17, cathepsin L, CD147 GRP78 may also function as receptors SARS-CoV-2.To determine expression
Transient adenovirus-mediated gene transfer of IL-1beta (AdIL-1beta), a proinflammatory cytokine, induces marked inflammation and severe progressive fibrosis in rat lungs. This is associated with an increase TGF-beta1 concentration bronchoalveolar lavage (BAL) fluid. key cytokine the process fibrogenesis, using intracellular signaling pathways involving Smad2 Smad3. In this study we investigate whether induced by able to independently induce lung mice deficient Smad3 gene. Seven days after...
Idiopathic pulmonary fibrosis (IPF) can lead to the development of secondary hypertension (PH) and ultimately death. Despite this known association, precise mechanism disease remains unknown. Using a rat model IPF, we explored role proangiogenic antiapoptotic growth factor VEGF in vascular remodeling that underlies PH. In model, adenoviral delivery active TGF-beta1 induces arterial remodeling, loss microvasculature fibrotic areas, increased pressure (PAP). Immunohistochemistry mRNA analysis...
Adhesion with macrophages promotes the activation of fibroblasts into myofibroblasts and creates a self-sustaining profibrotic niche.
Matrix stiffening with downstream activation of mechanosensitive pathways is strongly implicated in progressive fibrosis; however, pathologic changes extracellular matrix (ECM) that initiate mechano-homeostasis dysregulation are not defined human disease. By integrated multiscale biomechanical and biological analyses idiopathic pulmonary fibrosis lung tissue, we identify increased tissue stiffness a function dysregulated post-translational collagen cross-linking rather than any concentration...
Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have been associated with fibrotic lung disease, although exactly how they modulate this process remains unclear. Here we investigated role of GRP78, main UPR regulator, in an experimental model injury fibrosis. Grp78(+/-) , Chop(-/-) wild type C57BL6/J mice were exposed to bleomycin by oropharyngeal intubation lungs examined at days 7 21. We demonstrate here that strongly protected from bleomycin-induced fibrosis, as...
Background In clinical trials, the two anti-interleukin (IL)-5 monoclonal antibodies (mAbs: mepolizumab and reslizumab) approved to treat severe eosinophilic asthma reduce exacerbations by ∼50–60%. Objective To observe response anti-IL-5 mAbs in a real-life setting, evaluate predictors of suboptimal response. Methods four Canadian academic centres, predefined end-points 250 carefully characterised moderate-to-severe asthmatic patients were collected prospectively assess mAbs. Suboptimal was...
Abstract Although recent evidence indicates that gp130 cytokines, Oncostatin M (OSM) and IL-6 are involved in alternative programming of macrophages, their role lung fibrogenesis is poorly understood. Here, we investigated the effect transient adenoviral overexpression OSM or mice during bleomycin-induced fibrosis. Lung fibrosis M2-like macrophage accumulation were assessed by immunohistochemistry, western blotting, gene expression flow cytometry. Ex-vivo isolated alveolar bone...
Idiopathic pulmonary fibrosis (IPF) is characterized by progressive fibroblast and myofibroblast proliferation, extensive deposition of extracellular matrix (ECM). Fibroblast growth factor-1 (FGF-1) belongs to the FGF family has been shown inhibit collagen production differentiation into myofibroblasts, revert epithelial–mesenchymal transition inhibiting TGF-β1 signalling pathways. However, precise role FGF-1 in not yet elucidated. In this study, we explore mechanisms underlying...
Idiopathic pulmonary fibrosis is a fatal lung disease characterized by progressive and excessive accumulation of myofibroblasts in the lung. Connective-tissue growth factor (CTGF) exacerbates radiation-induced fibrosis, this study, we demonstrate upregulation CTGF rat model induced an adenovirus vector encoding active TGF-β1 (AdTGF-β1). We show that also upregulated patients with idiopathic fibrosis. Expression was vascular smooth muscle cells cultured from fibrotic lungs on Days 7 14 as...
Rationale: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by progressive scarring. IPF-related vascular remodeling and hypertension (PH) result in particularly poor prognosis. Objectives: To study the pathogenesis of fibrotic lungs its contribution to progression fibrosis. Methods: We used an experimental model associated with PH transient overexpression active TGF-β1 (transforming growth factor-β1). Samples from patients diseases were analyzed depth using...
Sarcoidosis is a systemic granulomatous disease of unknown cause. Natural improvement with favorable outcome common, but significant number patients present difficult to manage and progressive disease. The identification biomarkers associated activity progression warranted. Extracellular heat shock protein 90 (HSP90) α signaling molecule released by cells that induces proinflammatory through interaction certain receptors, such as lipoprotein receptor-related 1. HSP90α expression in lung...
The individual susceptibility to pulmonary fibrosis (PF) remains a mystery, suggesting role for genetic predisposition. pathogenesis of PF involves multitude factors mediating crosstalk between various tissue components. Some factors, such as transforming growth factor beta, are recognized key elements in the process, whereas others, connective (CTGF), is unclear. We investigated if Balb/c mice, known be resistant partly due lack CTGF induction upon stimulation with bleomycin, can...
An increasing number of drugs are recognized to induce distinctive patterns infiltrative lung disease (ILD), ranging from benign infiltrates life-threatening adult respiratory distress syndromes. In addition drugs, biomolecules such as proteins and cytokines, medicinal plants also capable inducing disease, some being severe and/or irreversible. For several reasons it is difficult estimate the exact frequency drug-induced (DI-ILD). The risk for DI-ILD clinical vary depending on a variety host...
Different forms of acute kidney injury (AKI) have been associated with endoplasmic reticulum (ER) stress; these include AKI caused by acetaminophen, antibiotics, cisplatin, and radiocontrast. Tunicamycin (TM) is a nucleoside antibiotic known to induce ER stress commonly used inducer AKI. 4-phenylbutyrate (4-PBA) an FDA approved substance in children who suffer from urea cycle disorders. 4-PBA acts as inhibitor aiding protein folding at the molecular level preventing misfolded aggregation....