A5056576556- Neonatal Respiratory Health Research
- Pediatric health and respiratory diseases
- Cystic Fibrosis Research Advances
- Asthma and respiratory diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Antimicrobial Peptides and Activities
- Tracheal and airway disorders
- Inhalation and Respiratory Drug Delivery
- Respiratory viral infections research
- Air Quality and Health Impacts
- Immunodeficiency and Autoimmune Disorders
- CRISPR and Genetic Engineering
- SARS-CoV-2 and COVID-19 Research
- Bacterial biofilms and quorum sensing
- Epigenetics and DNA Methylation
- Bacterial Genetics and Biotechnology
- Pluripotent Stem Cells Research
- Renal and related cancers
- SARS-CoV-2 detection and testing
- Neonatal and Maternal Infections
- Evolution and Genetic Dynamics
- Climate Change and Health Impacts
- Gut microbiota and health
- Inflammation biomarkers and pathways
- Infection Control and Ventilation
Utrecht University
2018-2025
University Medical Center Utrecht
2018-2025
Wilhelmina Children's Hospital
2018-2025
Leiden University Medical Center
2012-2024
Leiden University
2010-2016
University of British Columbia
2010
Resource14 January 2019Open Access Transparent process Long-term expanding human airway organoids for disease modeling Norman Sachs Oncode Institute, Hubrecht Institute-KNAW and UMC Utrecht, The Netherlands Search more papers by this author Angelos Papaspyropoulos Domenique D Zomer-van Ommen Wilhelmina Children's Hospital Inha Heo Lena Böttinger Dymph Klay St. Antonius Nieuwegein, Fleur Weeber Cancer Amsterdam, Guizela Huelsz-Prince FOM Institute AMOLF, Nino Iakobachvili Maastricht...
The generation of protective secretory IgA relies on the epithelial polymeric immunoglobulin receptor (pIgR). pIgR expression is reduced in chronic obstructive pulmonary disease (COPD), but correlation to severity and underlying mechanisms remains unknown.To address hypothesis that down-regulation COPD concerns severe relation aberrant programming bronchial epithelium.Surgical lung tissue primary epithelium (cultured air-liquid interface, ALI) obtained from a large series patients (n = 116)...
Mesenchymal stromal cells (MSCs) are investigated for their potential to reduce inflammation and repair damaged tissue. Inflammation tissue damage hallmarks of chronic obstructive pulmonary disease (COPD) MSC infusion is a promising new treatment COPD. Inflammatory mediators attract MSCs sites affect immune-modulatory properties, but little known about effect on regenerative properties MSCs. This study investigates the pro-inflammatory cytokines TNF-α IL-1β MSCs, using an in vitro wound...
Abstract Basal cells play a critical role in the response of airway epithelium to injury and are recently recognized also contribute epithelial immunity. Antimicrobial proteins peptides essential effector molecules this innate However, little is known about specific basal antimicrobial protein peptide production regulation ubiquitous RNase 7. In study, we report that principal cell type producing 7 cultured primary bronchial (PBEC). Exposure submerged PBEC (primarily consisting cells)...
Antimicrobial proteins and peptides (AMPs) are a central component of the antibacterial activity airway epithelial cells. It has been proposed that decrease in lung defense contributes to an increased susceptibility microbial infection smokers patients with chronic obstructive pulmonary disease (COPD). However, whether reduced AMP expression epithelium this lower is largely unknown. We investigated bacterial killing AMPs by air-liquid interface-cultured primary bronchial cells from COPD...
It is currently unknown how cigarette smoke-induced airway remodelling affects highly expressed respiratory epithelial defence proteins and thereby mucosal host defence. Localisation of a selected set was assessed in well-differentiated primary bronchial cell (PBEC) cultures. Next, PBEC were cultured at the air–liquid interface, during differentiation for 2–3 weeks exposed daily to whole smoke. Gene expression, protein levels markers subsequently assessed. In addition, functional activities...
Cystic fibrosis is caused by genetic defects that impair the CFTR channel in airway epithelial cells. These may be overcome specific modulating drugs, for which efficacy can predicted a personalized manner using 3D nasal-brushing–derived organoids forskolin-induced swelling assay. Despite of this, previously described function assays were not fully optimal, because inefficient organoid differentiation and limited scalability. In this report, we therefore describe an alternative method...
Cigarette smoking is the main risk factor associated with chronic obstructive pulmonary disease (COPD), and contributes to COPD development progression by causing epithelial injury inflammation. Whereas it known that cigarette smoke (CS) may affect innate immune function of airway cells repair, this has so far not been explored in an integrated design using mucociliary differentiated cells. In study, we examined effect whole CS exposure on wound repair activity primary bronchial cells, upon...
Activin-A is a pleiotropic cytokine belonging to the transforming growth factor-β superfamily and has been implicated in asthma pulmonary fibrosis. However, role of activin-A its endogenous inhibitor, follistatin, pathogenesis chronic obstructive disease (COPD) unknown. We first quantified follistatin lungs air- or cigarette smoke-exposed mice patients with COPD by immunohistochemistry, ELISA quantitative real-time PCR. subsequently studied effect smoke on primary human bronchial epithelial...
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Pseudomonas aeruginosa is a Gram-negative bacterium that notorious for airway infections in cystic fibrosis (CF) subjects. Bacterial quorum sensing (QS) coordinates virulence factor expression and biofilm formation at population level. Better understanding of QS the bacterium-host interaction required. Here, we set up new P. infection model, using 2D upper nasal organoids were derived from 3D organoids. Using dual RNA-sequencing, dissected between organoid epithelial cells WT or QS-mutant...
Aberrant activity of a disintegrin and metalloprotease 17 (ADAM17), also known as TACE, epidermal growth factor receptor (EGFR) has been suggested to contribute chronic obstructive pulmonary disease (COPD) development progression. The aim this study was investigate the role these proteins in activation primary bronchial epithelial cells differentiated at air-liquid interface (ALI-PBEC) by whole cigarette smoke (CS), comparing from COPD patients with non-COPD CS exposure ALI-PBEC enhanced...
The nasal cavity displays immune tolerance to commensal bacteria under homeostatic conditions, which is rapidly converted a pro-inflammatory response upon infection. Yet, the factors that control this conversion are still largely unknown. Here, we provide evidence Fc gamma receptor III (FcγRIII) stimulation breaks in human through activation of epithelial cells, first line defense against invading microbes. While steady-state conditions cells were completely non-responsive Gram-negative P....
INTRODUCTION Our lungs have a vital role in mediating the exchange of oxygen and carbon dioxide between air we breathe body. This function is under constant pressure as inhaled contains numerous particles, gasses, microorganisms that may cause injury infection to lungs. Removal neutralization potential harmful substances from main airway epithelium. pseudo-stratified layer cells covers surface conducting airways plays an important protecting alveoli, where gas takes place, injury. The...
We present a protocol to generate organoids from air-liquid-interface (ALI)-differentiated nasal epithelia. detail their application as cystic fibrosis (CF) disease model in the transmembrane conductance regulator (CFTR)-dependent forskolin-induced swelling (FIS) assay. describe steps for isolation, expansion and cryostorage of brushing-derived basal progenitor cells, differentiation ALI cultures. Furthermore, we conversion differentiated epithelial fragments into healthy controls CF...
<title>Abstract</title> Although vaccines and treatments have strengthened our ability to combat the COVID-19 pandemic, new variants of SARS-CoV-2 continue emerge in human populations. Because evolution is driven by mutation, a better understanding its mutation rate spectrum could improve forecast trajectory pandemic. Here, we used circular RNA consensus sequencing (CirSeq) determine six performed short-term experiment impact these mutations on viral fitness. Our analyses indicate that...
Individuals with cystic fibrosis (CF) suffer from severe respiratory disease due to a genetic defect in the transmembrane conductance regulator (CFTR) gene, which impairs airway epithelial ion and fluid secretion. New CFTR modulators that restore mutant function have been recently approved for large group of people CF (pwCF), but ~19% pwCF cannot benefit Restoration secretion through non-CFTR pathways might be an effective treatment all pwCF. Here, we developed medium-throughput 384-well...
In cystic fibrosis (CF), defects in the CF transmembrane conductance regulator (CFTR) channel lead to an acidic airway surface liquid (ASL), which compromises innate defence mechanisms, predisposing pulmonary failure. Restoring ASL pH is a potential therapy for people with CF, particularly those who cannot benefit from current highly effective modulator therapy. However, we lack comprehensive understanding of complex mechanisms underlying regulation. The calcium-activated chloride channel,...
Abstract A better understanding of host cell remodeling by the coronavirus SARS-CoV-2 is urgently needed to understand viral pathogenesis and guide drug development. Expression profiling electron microscopy have frequently been used study virus-host interactions, but these techniques do not readily enable spatial, sub-cellular molecular analysis specific cellular compartments. Here, we use diffraction-unlimited fluorescence analyze how infection exploits repurposes subcellular architecture...
Recurrent respiratory syncytial virus (RSV) infection requiring hospitalization is rare and the underlying mechanism unknown. We aimed to determine role of CD14-mediated immunity in pathogenesis recurrent RSV infection.We performed genotyping longitudinal immunophenotyping first patient with a genetic CD14 deficiency who developed infection. analyzed gene expression profiles interleukin (IL)-6 production by peripheral blood mononuclear cells response pre- post-fusion (F) protein. generated...