A5074997110- Neonatal Respiratory Health Research
- Asthma and respiratory diseases
- Cancer Cells and Metastasis
- Cellular Mechanics and Interactions
- Inhalation and Respiratory Drug Delivery
- Cell Adhesion Molecules Research
- Smoking Behavior and Cessation
- Ultrasound and Hyperthermia Applications
- Cytokine Signaling Pathways and Interactions
- Medical Imaging and Pathology Studies
- Mesenchymal stem cell research
- Respiratory viral infections research
- Occupational exposure and asthma
- Sphingolipid Metabolism and Signaling
- Respiratory Support and Mechanisms
- Molecular Biology Techniques and Applications
- Advanced Biosensing Techniques and Applications
- Tracheal and airway disorders
- Tissue Engineering and Regenerative Medicine
- Extracellular vesicles in disease
- Coronary Artery Anomalies
- Cerebrovascular and genetic disorders
- Genomics, phytochemicals, and oxidative stress
- Epigenetics and DNA Methylation
- Immune cells in cancer
Harvard University
2018-2023
McGill University Health Centre
2013-2021
Christie (Canada)
2014-2021
McGill University
2014-2019
Naval Medical Center San Diego
1972
Abstract The epithelial-to-mesenchymal transition (EMT) and the unjamming (UJT) each comprises a gateway to cellular migration, plasticity remodeling, but extent which these core programs are distinct, overlapping, or identical has remained undefined. Here, we triggered partial EMT (pEMT) UJT in differentiated primary human bronchial epithelial cells. After triggering UJT, cell-cell junctions, apico-basal polarity, barrier function remain intact, cells elongate align into cooperative...
The widespread use of electronic cigarettes (e-cigarettes or e-cig) is a growing public health concern. Diacetyl and its chemical cousin 2,3-pentanedione are commonly used to add flavors e-cig; however, little known about how the flavoring chemicals may impair lung function. Here we report that induce transcriptomic changes perturb cilia function in airway epithelium. Using RNA-Seq, identified total 163 568 differentially expressed genes primary normal human bronchial epithelial (NHBE) cells...
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Abstract Bronchospasm compresses the bronchial epithelium, and this compressive stress has been implicated in asthma pathogenesis. However, molecular mechanisms by which alters pathways relevant to disease are not well understood. Using air-liquid interface cultures of primary human epithelial cells derived from non-asthmatic donors asthmatic donors, we applied a then used network approach map resulting changes interactome. In compression itself was sufficient induce inflammatory, late...
During acute bronchoconstriction, the airway epithelium becomes mechanically compressed, as smooth muscle contracts and narrows. This mechanical compression activates to promote asthmatic remodeling. However, whether compressed can feed back on cause of bronchoconstriction has remained an open question. Here we examine potential for epithelial augment proliferation contraction muscle, thus potentiate further compression. Well-differentiated primary human bronchial (HBE) cells maintained in...
Oxidative stress in allergic asthma may result from oxidase activity or proinflammatory molecules pollens. Signaling via TLR4 and its adaptor Toll-IL-1R domain-containing adapter inducing IFN-β (TRIF) has been implicated reactive oxygen species-mediated acute lung injury Th2 immune responses. We investigated the contributions of oxidative TLR4/TRIF signaling to experimental induced by birch pollen exposure exclusively airways. Mice were exposed native heat-inactivated white extract (BPEx)...
The healthy and mature epithelial layer is ordinarily quiescent, non-migratory, solid-like, jammed. However, in a variety of circumstances the transitions to phase that dynamic, migratory, fluid-like unjammed. This has been demonstrated developing embryo, avian airway, reconstituted
Temporal RNA-seq data reveal genomic signatures of the unjamming transition in compressed human bronchial epithelial cells.
The airway epithelium may release pro-inflammatory cytokines and chemokines in the asthmatic airway. Sphingosine 1-phosphate (S1P) is a bioactive lipid, increased airways of asthmatics, that trigger potent neutrophil chemoattractant Interleukin-8 (IL-8) by epithelial cells. S1P ligand for 5 G protein-coupled receptors, S1PR1-5. We wished to explore mechanisms induced IL-8 secretion with regard receptor(s) downstream signaling events involved. Our results indicate mediated S1PR2 transcription...
Background and Purpose Cysteinyl leukotrienes (CysLTs) are pro‐inflammatory lipid mediators that exacerbate disease state in several asthma phenotypes including induced by allergen, virus exercise. However, the role of CysLTs irritant‐induced airway is not well characterized. The purpose current study was to investigate effect montelukast, a CysLT 1 receptor antagonist, on parameters inhalation chlorine mouse. Experimental Approach BALB/c mice were exposed air (100 ppm, for 5 min)....
The COVID-19 pandemic is an ongoing threat to public health. Since the identification of COVID-19, disease caused by SARS-CoV-2, no drugs have been developed specifically target SARS-CoV-2. To develop effective and safe treatment options, a better understanding cellular mechanisms underlying SARS-CoV-2 infection required. fill this knowledge gap, researchers require reliable experimental systems that express host factor proteins necessary for entry These include viral receptor,...
Aberrant remodeling of the asthmatic airway is not well understood but thought to be attributable in part mechanical compression epithelial cells. Here, we examine compression-induced expression and secretion extracellular matrix protein tenascin C (TNC) from well-differentiated primary human bronchial (HBE) cells grown an air-liquid interface culture. We measured TNC mRNA using RT-qPCR secreted Western blotting ELISA. To determine intracellular signaling pathways, used specific inhibitors...
The increased mass of airway smooth muscle (ASM) in the airways asthmatic patients may contribute to pathology this disease by increasing capacity for narrowing. Evidence epithelium as a participant ASM remodeling is accruing. To investigate mechanisms which epithelial cells induce cell (ASMC) proliferation, we have employed co-culture model explore markers ASMC proliferative phenotype. Co-culture with led incorporation bromodeoxyuridine into ASMCs, indicating augmented proliferation and an...
Abstract Every organ surface and body cavity is lined by a confluent collective of epithelial cells. In homeostatic circumstances the remains effectively solid-like sedentary. But during morphogenesis, remodeling or repair, as well malignant invasion metastasis, becomes fluid-like migratory 1–4 . This conversion from sedentary to behavior has traditionally been understood manifestation epithelial-to-mesenchymal transition (EMT) partial EMT (pEMT) 5–8 However, in certain contexts this...
ABSTRACT Under homeostatic conditions, epithelial cells remain non-migratory. However, during embryonic development and pathological they become migratory. The mechanism underlying the transition of layer between non-migratory migratory phases is a fundamental question in biology. Using well-differentiated primary human bronchial that form pseudostratified epithelium, we have previously identified confluent can from to phase through an unjamming (UJT). We defined collective cellular...
Abstract Activated CD4 T cells connect to airway smooth muscle (ASMCs) in vitro via lymphocyte-derived membrane conduits (LMCs) structurally similar nanotubes with unknown intercellular signals triggering their formation. We examined the structure and function of cell–derived LMCs, we established a role for ASMC-derived basic fibroblast growth factor 2 (FGF2b) FGF receptor (FGFR)1 LMC Blocking FGF2b’s synthesis FGFR1 reduced Mitochondrial flux from ASMCs was partially FGF2b dependent....
Abstract The widespread use of electronic cigarettes (e-cig) is a serious public health concern; however, mechanisms by which e-cig impair the function airway epithelial cells—the direct target smoke—are not fully understood. Here we report transcriptomic changes, including decreased expression many ribosomal genes, in cells response to exposure. Using RNA-seq identify over 200 differentially expressed genes air–liquid interface cultured primary normal human bronchial (NHBE) exposed smoke...
Rhinovirus (RV) infection of airway epithelial cells triggers asthma exacerbations, during which smooth muscle (ASM) excessively contracts. Due to ASM contraction, become mechanically compressed. We previously reported that compressed human bronchial (HBE) are a source endothelin-1 (ET-1) causes contraction. Here, we hypothesized sensing RV by TLR3 and compression induce ET-1 secretion through TGF-β receptor (TGFβR)-dependent mechanism. To test this, used primary HBE well-differentiated in...
Airway smooth muscle cells (ASMCs) are phenotypically regulated to exist in either a proliferative or contractile state. However, the influence of other airway structural cell types on ASMC phenotype is largely unknown. Although epithelial known drive ASM proliferation, their effects uncertain. In current study, we tested hypothesis that reduce ASMCs. To do so, measured force production by traction microscopy, gene and protein expression, as well calcium release Fura-2 ratiometric imaging....
Bone marrow stromal cells (BMSCs) contain a subset of multipotent stem cells. Here, we demonstrate that serotonin, biogenic amine released by platelets and mast cells, can induce the smooth muscle differentiation BMSCs. Brown Norway rat BMSCs stimulated with serotonin had increased expression markers myosin heavy chain (MHC) α actin (α-SMA) qPCR Western blot, indicating differentiation. This was accompanied concomitant down-regulation microRNA miR-25-5p, which found to negatively regulate...
Cystic fibrosis (CF) is a genetic disease that causes multiple airway abnormalities. Two major respiratory consequences of CF are hyperresponsiveness (AHR) and remodeling. Airway smooth muscle (ASM) hypothesized to be responsible for the dysfunction, since their thickening involved in remodeling, excessive contraction by ASM may cause AHR. It unclear whether intrinsically altered favor increased contractility or proliferation if microenvironmental influences induce pathological behavior...