A5004657168- Asthma and respiratory diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Neonatal Respiratory Health Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- IL-33, ST2, and ILC Pathways
- Pediatric health and respiratory diseases
- Autophagy in Disease and Therapy
- Caveolin-1 and cellular processes
- Inhalation and Respiratory Drug Delivery
- Wnt/β-catenin signaling in development and cancer
- Respiratory and Cough-Related Research
- Cell Adhesion Molecules Research
- Receptor Mechanisms and Signaling
- Medical Imaging and Pathology Studies
- Immune Response and Inflammation
- Ion channel regulation and function
- S100 Proteins and Annexins
- Axon Guidance and Neuronal Signaling
- Pulmonary Hypertension Research and Treatments
- Peptidase Inhibition and Analysis
- Neuropeptides and Animal Physiology
- Immune Cell Function and Interaction
- Ion Channels and Receptors
- Protein Kinase Regulation and GTPase Signaling
- Tracheal and airway disorders
University of Manitoba
2016-2025
Children's Hospital Research Institute of Manitoba
2016-2025
Breathing Buildings (United Kingdom)
2025
Research Manitoba
2014-2024
Research Institute of General Pathology and Pathophysiology, the Russian Academy of Medical Sciences
2023
Université de Saint-Boniface
2023
McMaster University
2020-2021
Canadian Respiratory Research Network
2016-2021
University of British Columbia
2015-2021
McMaster University Medical Centre
2021
Abstract IL-33, a new member of the IL-1 cytokine family, promotes Th2 inflammation, but evidence on implications this in asthma is lacking. IL-33 would be mainly expressed by structural cells, whether proinflammatory cytokines modulate its expression airway smooth muscle cells (ASMC) unknown. Endobronchial biopsies were obtained from adults with mild (n = 8), moderate severe 9), and control subjects 5). Immunocytochemistry, laser-capture microdissection, reverse transcriptase, real-time...
Abstract Transforming growth factor- β 1 (TGF- ) is an important regulator of fibrogenesis in heart disease. In many other cellular systems, TGF- may also induce autophagy, but a link between its fibrogenic and autophagic effects unknown. Thus we tested whether or not -induced autophagy has regulatory function on fibrosis human atrial myofibroblasts (hATMyofbs). Primary hATMyofbs were treated with to assess for responses. Using immunoblotting, immunofluorescence transmission electron...
Progressive fibrosing interstitial lung disease (PF-ILD) is characterised by progressive physiological, symptomatic and/or radiographic worsening. The real-world prevalence and characteristics of PF-ILD remain uncertain.Patients were enrolled from the Canadian Registry for Pulmonary Fibrosis between 2015 2020. was defined as a relative forced vital capacity (FVC) decline ≥10%, death, transplantation or any two of: FVC ≥5% <10%, worsening respiratory symptoms fibrosis on computed tomography...
Airway smooth muscle plays a principal role in the pathogenesis of asthma. Primary cultures are being used to investigate airway myocyte proliferation and cellular pathways regulating contraction. cells (SMC) modulate from contractile noncontractile phenotype culture, but no systematic study concomitant changes expression cytocontractile cytoskeletal proteins has been reported. We measured temporal protein marker canine tracheal SMC primary using specific antibodies cDNA probes. Immunoblot...
Chronic inflammation in asthma and chronic obstructive pulmonary disease drives pathological structural remodelling of the airways. Using tiotropium bromide, acetylcholine was recently identified as playing a major regulatory role airway smooth muscle guinea pig model ongoing allergic asthma. The aim present study to investigate other aspects compare effectiveness glucocorticosteroid budesonide. Ovalbumin-sensitised pigs were challenged for 12 weeks with aerosolised ovalbumin. ovalbumin...
Chronic airways diseases, including asthma, are associated with an increased airway smooth muscle (ASM) mass, which may contribute to chronic hyperresponsiveness. Increased mass is due, in part, ASM proliferation, although the precise molecular mechanisms for this response not completely clear. Caveolae, abundant cells, membrane microdomains where receptors and signaling effectors can be sequestered. We hypothesized that caveolae caveolin-1 play important regulatory role proliferation....
Abstract Brevinin‐2R is a novel non‐hemolytic defensin that was isolated from the skin of frog Rana ridibunda . It exhibits preferential cytotoxicity towards malignant cells, including Jurkat (T‐cell leukemia), BJAB (B‐cell lymphoma), HT29/219, SW742 (colon carcinomas), L929 (fibrosarcoma), MCF‐7 (breast adenocarcinoma), A549 (lung carcinoma), as compared to primary cells peripheral blood mononuclear (PBMC), T and human lung fibroblasts. overexpressing Bcl2, over‐expressing dominant‐negative...
Thymic stromal lymphopoietin (TSLP) is a novel cytokine that triggers dendritic cell-mediated T helper (Th)-2 inflammatory responses. Previous studies have demonstrated human airway smooth muscle cells (HASMC) play critical role in initiating or perpetuating inflammation by producing chemokines and cytokines. In this study, we first evaluated the expression of TSLP primary HASMC investigated how proinflammatory cytokines (TNF-α IL-1β) Th-2 (IL-4, IL-9) regulate production from HASMC. mRNA...
Defining mechanisms by which differentiated, contractile smooth muscle cells become proliferative and secretory in response to mechanical environmental stress is crucial for determining the contribution of airway (ASM) inflammatory responses that result disease. Regulation microRNAs (miRNAs) has emerged as an important post-transcriptional mechanism regulating gene expression may modulate ASM phenotype, but little known about functions miRNA muscle. In present study we used microarrays...
Increased airway smooth muscle (ASM) mass is a hallmark of remodeling in severe asthma. Th17-associated cytokines, particularly IL-17A, IL-17F, and IL-22, have been postulated to play role the pathogenesis To investigate vitro effect Th17 cytokines on proliferation survival cells (ASMCs), human ASMCs from asthmatic nonasthmatic subjects were incubated with or IL-22. The aforementioned demonstrated an ability promote subjects, which mediated by selective activation their corresponding...
Structural cell migration plays a central role in the pathophysiology of several diseases, including asthma. Previously, we established that IL-17-induced (CXCL1, CXCL2, and CXCL3) production promoted airway smooth muscle (ASMC) migration, consequently sought to investigate molecular mechanism CXC-induced ASMC migration. Recombinant human CXCL1, CXCL3 were used assess primary ASMCs from normal asthmatic subjects using modified Boyden chamber. Neutralizing Abs or small interfering RNA (siRNA)...
3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins) are cholesterol-lowering drugs that exert other cellular effects and underlie their beneficial health effects, including those associated with myocardial remodeling. We recently demonstrated statins induces apoptosis autophagy in human lung mesenchymal cells. Here, we extend our knowledge showing simultaneously activation of the apoptosis, unfolded protein response (UPR) primary atrial fibroblasts (hATF). Thus tested degree to...
Idiopathic pulmonary fibrosis (IPF) is a lethal fibrotic lung disease in adults with limited treatment options. Autophagy and the unfolded protein response (UPR), fundamental processes induced by cell stress, are dysregulated fibroblasts epithelial cells from humans IPF. Human primary cultured parenchymal airway non-IPF IPF donors were stimulated transforming growth factor-β1 (TGF-β1) or without inhibitors of autophagy UPR (IRE1 inhibitor). Using immunoblotting, we monitored temporal changes...
MicroRNA (miR)-146a and miR-146b are negative regulators of inflammatory gene expression in lung fibroblasts, epithelial cells, monocytes, endothelial cells. The abundance cyclooxygenase-2 (COX-2) IL-1β is negatively regulated by the miR-146 family, suggesting miR-146a and/or might modulate mediator airway smooth muscle thereby contributing to pathogenesis asthma. To test this idea we compared human cells (hASMCs) from nonasthmatic asthmatic subjects treated with cytomix (IL-1β, TNF-α, IFNγ)...
Transforming growth factor β (TGF-β), a key mediator of fibrotic responses, is increased in asthma and drives airway remodeling by inducing expression extracellular matrix (ECM) proteins. We investigated the molecular mechanisms underlying TGF-β-induced ECM smooth muscle cells demonstrate novel link between TGF-β Wingless/integrase 1 (WNT) signaling deposition. Airway expresses abundant WNT ligands, with noncanonical WNT-5A being most profoundly expressed. Interestingly, shows ∼2-fold higher...
Autophagy and apoptosis are two major interconnected host cell responses to viral infection, including influenza A virus (IAV). Thus, delineating these events could facilitate the development of better treatment options provide an effective anti-viral strategy for controlling IAV infection. We used A549 cells mouse embryonic fibroblasts (MEF) study role virus-induced autophagy apoptosis, cross-talk between both pathways, their relation infection [ATCC strain A/Puerto Rico/8/34(H1N1)...
Airway remodeling (AR) is a prominent feature of asthma and other obstructive lung diseases that minimally affected by current treatments. The goals this Official American Thoracic Society (ATS) Research Statement are to discuss the scientific, technological, economic, regulatory issues deter progress AR research development therapeutics targeting propose approaches solutions these specific problems. This not intended provide clinical practice recommendations on any disease in which observed...
We tested the hypothesis that prolonged serum deprivation would allow a subset of cultured airway myocytes to reacquire abundant contractile protein content, marked shortening capacity, and elongated morphology characteristic cells within intact tissue. Passage 1 or 2 canine tracheal smooth muscle (SM) were grown confluence, then deprived for up 19 days. During deprivation, two differentiation pathways emerged. One-sixth developed an aligned into bundles. Elongated contained cables...
RhoA and its downstream target Rho kinase regulate serum response factor (SRF)-dependent skeletal smooth muscle gene expression. We previously reported that long-term deprivation reduces transcription of contractile apparatus encoding genes, by redistributing SRF out the nucleus. Because components stimulate activity, these observations suggest hypothesis RhoA/Rho pathway regulates SRF-dependent in part controlling subcellular localization. Our present results support this hypothesis:...
Recently, IL-17A has been shown to be expressed in higher levels respiratory secretions from asthmatics and correlated with airway hyperresponsiveness. Although these studies raise the possibility that may influence allergic disease, mechanisms remain unknown. In this study, we investigated molecular involved IL-17A-mediated CC chemokine (eotaxin-1/CCL11) production human smooth muscle (ASM) cells. We found incubation of ASM cells rIL-17A resulted a significant increase eotaxin-1/CCL11...