A5077426550- Asthma and respiratory diseases
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Neonatal Respiratory Health Research
- Pulmonary Hypertension Research and Treatments
- Respiratory and Cough-Related Research
- Pediatric health and respiratory diseases
- Proteoglycans and glycosaminoglycans research
- RNA and protein synthesis mechanisms
- Inhalation and Respiratory Drug Delivery
- Protease and Inhibitor Mechanisms
- Cytokine Signaling Pathways and Interactions
- Peptidase Inhibition and Analysis
- Cancer-related gene regulation
- Respiratory viral infections research
- RNA Research and Splicing
- Eicosanoids and Hypertension Pharmacology
- Immune Response and Inflammation
- Ecology, Conservation, and Geographical Studies
- Transplantation: Methods and Outcomes
- IL-33, ST2, and ILC Pathways
- Estrogen and related hormone effects
- Cell Adhesion Molecules Research
- Religion, Theology, and Education
- Inflammatory Bowel Disease
George Washington University
2025
University Hospital of Basel
2015-2024
University of Basel
2014-2024
Naval Medical Center Portsmouth
2024
Massachusetts General Hospital
2024
Staatliche Museen zu Berlin
2023
Georgetown University
2023
Hospital Base
2009-2022
University of Stuttgart
2022
Fulcrum Therapeutics (United States)
2022
Skin aging is a multifactorial process consisting of two distinct and independent mechanisms: intrinsic extrinsic aging. Youthful skin retains its turgor, resilience pliability, among others, due to high content water. Daily external injury, in addition the normal aging, causes loss moisture. The key molecule involved moisture hyaluronic acid (HA) that has unique capacity retaining There are multiple sites for control HA synthesis, deposition, cell protein association degradation, reflecting...
We demonstrate that four different proteins from calf thymus are able to restore splicing in the same splicing-deficient extract using several pre-mRNA substrates. These members of a conserved family recognized by monoclonal antibody binds active sites RNA polymerase II transcription. purified this nuclear phosphoproteins apparent homogeneity two salt precipitations. The family, called SR for their serine- and arginine-rich carboxy-terminal domains, consists at least five with molecular...
Increased airway smooth muscle (ASM) within the bronchial wall of asthmatic patients has been well documented and is likely to be result increased proliferation. We have for first time able culture ASM cells from compare their proliferation rate with that nonasthmatic patients. Asthmatic cell cultures (n = 12) were established explanted lungs endobronchial biopsies. Nonasthmatic 10) obtained tissue no disease, emphysema, carcinoma, fibrosing alveolitis. Cell counts, tritiated thymidine...
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. The kinase inhibitor nintedanib specific for vascular endothelial growth factor receptor (VEGFR), platelet-derived (PDGFR) and fibroblast (FGFR) significantly reduced the rate of decline forced vital capacity versus placebo.To determine in vitro effect on primary human fibroblasts.Fibroblasts were isolated from lungs IPF patients non-fibrotic controls. We assessed VEGF, PDGF-BB basic FGF (bFGF) ± on: (i)...
Abstract Silica particles induce lung inflammation and fibrosis. Here we show that stimulator of interferon genes (STING) is essential for silica-induced inflammation. In mice, silica induces cell death self-dsDNA release in the bronchoalveolar space activates STING pathway. Degradation extracellular by DNase I inhibits activation downstream type IFN response. Patients with silicosis have increased circulating dsDNA CXCL10 sputum, patients fibrotic interstitial disease display lung. vitro,...
The glucocorticoid receptor (GR) is a ubiquitously expressed transcription factor present in most cell types. Upon ligand binding, the GR activated and translocates into nucleus where it transmits anti-inflammatory actions of glucocorticoids. Here, we describe ligand-independent activation by β2-adrenergic (β2-AR) agonists, salbutamol salmeterol, primary human lung fibroblasts vascular smooth muscle cells. Immunohistochemistry demonstrated expression β2-AR Treatment cells with or resulted...
An antibody was identified previously that recognizes sites of polymerase II transcription on lampbrush chromosomes, puffs polytene and many small granules in the nucleoplasm all cells tested. This binds a conserved family phosphorylated polypeptides vertebrate invertebrate cells. We developed method for purifying these proteins involves differential solubility MgCl2. isolated Drosophila cDNA encoding one using information obtained from microsequencing. In vivo expression studies show this...
Increased proliferation of bronchial smooth-muscle cells may lead to increased muscle mass in the airways patients with asthma. The antiproliferative effect glucocorticoids subjects without asthma is mediated by a complex glucocorticoid receptor and CCAAT/enhancer binding protein alpha (C/EBPalpha). We examined signaling pathway controlling inhibitory on cell interleukin-6 synthesis those asthma.Lines were established from 20 asthma, 8 emphysema, 26 control subjects. Cell was determined...
Cardiac hypertrophy is largely due to cardiac fibroblast growth and increased synthesis of extracellular matrix. This study has investigated the contribution vasoactive hormone, angiotensin II, toward this hypertrophic process. We have demonstrated that cultures adult rat fibroblasts express AT1 but not AT2 receptors for II. The ability II stimulate phosphoinositide catabolism elevate intracellular calcium concentrations in these cells was blocked by losartan, a specific receptor antagonist,...
Vascular endothelial growth factor (VEGF) is a potent peptide specific for vascular cells, which promotes neovascularization and increases permeability in vivo. Enhanced microvascular edema are common characteristics of inflammatory neoplastic disorders. Two proinflammatory mediators, platelet-activating (PAF) platelet-derived (PDGF), known to contribute cellular damage tissue remodeling number lung diseases. To determine whether PAF or PDGF induce VEGF gene expression primary cultures human...
Increased collagen and extracellular matrix (ECM) deposition within the lung is a characteristic feature of fibrosis. Transforming growth factor (TGF)-β isoforms play pivotal role in production ECM. In this study, we investigated effects TGF-β1 TGF-β3 on main processes controlling ECM using primary human fibroblasts. We analyzed 1) metabolism by [ 3 H]proline incorporation, 2) metalloproteinase (MMP) expression substrate gel zymography, 3) tissue inhibitor metalloproteinases (TIMP) Western...
An mAb library was produced against proteins from the germinal vesicle (GV) of frog Xenopus laevis; 104 selected this on basis its immunofluorescent staining lampbrush chromosome loops. Chromosomes several species frogs and salamanders stained equally well. The antibody also surface numerous small granules in GV nucleoplasm. interior same by antibodies nuclear ribonucleoproteins (snRNPs). somatic nuclei many vertebrate invertebrate species, usually a finely punctate pattern similar to that...
Background: Rhinovirus infection is responsible for considerable morbidity and mortality as the major cause of exacerbations asthma, also known to induce cystic fibrosis chronic obstructive pulmonary disease. Exacerbations these diseases are frequently associated with bacterial atypical infection. Alveolar macrophages immune cells in airways important defence against infections. Methods: The authors investigated whether rhinovirus modifies cytokine release, pattern recognition receptor...
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...
Transforming growth factor (TGF)-β1 induces extracellular matrix deposition and proliferation of mesenchymal cells. We recently reported that interleukin (IL)-6 is an essential mediator factor-induced lung fibroblasts. Here, we demonstrate by reverse transcriptase polymerase chain reaction enzyme-linked immunoassay TGF-β1 a potent inducer IL-6 mRNA protein in primary human Transient transfections fibroblasts with luciferase reporter gene construct containing nucleotides −651 to +1 the...
The extracellular matrix (ECM) is an intricate network composed of array macromolecules capable regulating the functional responsiveness cells. Its composition greatly varies among different types tissue, and dysregulation its metabolism may contribute to vascular remodeling during pathogenesis various diseases, including atherosclerosis. In view their antiatherosclerotic effects, role Ca2+ channel blockers in ECM was examined. Nanomolar concentrations five amlodipine, felodipine,...
If pre-mRNA splicing begins during RNA synthesis, then transcriptionally active genes may be expected to contain high concentrations of factors. However, previous studies have localized factors a network "speckles," which is distinct from individual sites gene transcription where spliced. Speckles been detected with antibodies specific for snRNPs and members the SR family Here we report that dilution these probes results in visualization hundreds throughout HeLa cell nucleus, size...