A5019306798- Neonatal Respiratory Health Research
- Asthma and respiratory diseases
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Glycosylation and Glycoproteins Research
- Cystic Fibrosis Research Advances
- Medical Imaging and Pathology Studies
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Pediatric health and respiratory diseases
- Respiratory and Cough-Related Research
- Lung Cancer Treatments and Mutations
- Inhalation and Respiratory Drug Delivery
- Tracheal and airway disorders
- Proteoglycans and glycosaminoglycans research
- Congenital Diaphragmatic Hernia Studies
- IL-33, ST2, and ILC Pathways
- Respiratory viral infections research
- Pulmonary Hypertension Research and Treatments
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- Carbohydrate Chemistry and Synthesis
- Infant Nutrition and Health
- Galectins and Cancer Biology
- Immunodeficiency and Autoimmune Disorders
- Pneumonia and Respiratory Infections
- Adenosine and Purinergic Signaling
University of Colorado Anschutz Medical Campus
2015-2025
University of Colorado Denver
2016-2025
University of Illinois Urbana-Champaign
2024-2025
University College Dublin
2023-2024
Rocky Mountain MS Center
2024
University of Colorado System
2017
National Jewish Health
2016
The University of Texas MD Anderson Cancer Center
2007-2013
University College London
2013
CRUK Lung Cancer Centre of Excellence
2013
The mutations that have been implicated in pulmonary fibrosis account for only a small proportion of the population risk.
De novo expression of Muc5ac, a mucin not normally expressed in the intestinal tract, is induced cecum mice resistant to Trichuris muris infection. In this study, we investigated role which detected shortly before worm expulsion and associated with production interleukin-13 (IL-13), resistance nematode. Muc5ac-deficient were incapable expelling T. from intestine harbored long-term chronic infections, despite developing strong T(H)2 responses. had elevated levels IL-13 and, surprisingly, an...
In asthma, airflow obstruction is thought to result primarily from inflammation-triggered airway smooth muscle (ASM) contraction. However, anti-inflammatory and muscle-relaxing treatments are often temporary or ineffective. Overproduction of the mucin MUC5AC an additional disease feature that, while strongly associated pathologically, poorly understood functionally. Here we show that Muc5ac a central effector allergic inflammation required for hyperreactivity (AHR) methacholine (MCh). mice...
The gain-of-function MUC5B promoter variant rs35705950 is the dominant risk factor for developing idiopathic pulmonary fibrosis (IPF). Here we show in humans that MUC5B, a mucin thought to be restricted conducting airways, co-expressed with surfactant protein C (SFTPC) type 2 alveolar epithelia and epithelial cells lining honeycomb cysts, indicating cell types involved lung distal airspace express MUC5B. In mice, demonstrate Muc5b concentration bronchoalveolar related impaired mucociliary...
Airway mucus hypersecretion is a prominent feature of many obstructive lung diseases. We thus determined the ontogeny and exocytic phenotype mouse airway mucous cells. In naive mice, ciliated (approximately 40%) nonciliated 60%) epithelial cells line airways, > 95% are Clara that contain cell secretory protein (CCSP). Mucous comprise < 5% After sensitization single aerosol antigen challenge, alcian blue-periodic acid Schiff's positive numbers increase dramatically, appearing 6 h after...
Mucus hypersecretion contributes to morbidity and mortality in many obstructive lung diseases. Gel-forming mucins are the chief glycoprotein components of airway mucus, elevated expression these during mucous metaplasia precedes hypersecretory phenotype. Five orthologous genes (MUC2, MUC5AC, MUC5B, MUC6, MUC19) encode mammalian gel-forming mucin family, several have been implicated asthma, cystic fibrosis, chronic pulmonary disease pathologies. However, absence a comprehensive analysis,...
Intercellular transfer of miR-223 from neutrophils to alveolar epithelial cells reduces lung inflammation in a mouse model ventilator-induced injury or pulmonary bacterial infection.
Abstract Pulmonary arterial hypertension (PAH) is an obstructive disease of the precapillary pulmonary arteries. Schistosomiasis-associated PAH shares altered vascular TGF-β signalling with idiopathic, heritable and autoimmune-associated etiologies; moreover, blockade can prevent experimental (PH) in pre-clinical models. regulated at level activation, but how activated this unknown. Here we show activation by thrombospondin-1 (TSP-1) both required sufficient for development PH Schistosoma...
The gain-of-function mucin 5B (MUC5B) promoter variant, rs35705950, confers the largest risk, genetic or otherwise, for development of idiopathic pulmonary fibrosis; however, mechanisms underlying regulation MUC5B expression have yet to be elucidated. Here, we identify a critical regulatory domain that contains variant and has highly conserved forkhead box protein A2 (FOXA2) binding motif. This region is differentially methylated in association with fibrosis, expression, rs35705950. In...
Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal lung disease. A maladaptive epithelium due to injury prominent feature contributor pathogenic cellular communication in IPF. Recent data highlight the concept of "reprogrammed" as critical development fibrosis. Extracellular vesicles (EVs) are potent mediator crosstalk, recent evidence supports their role pathologies such Here, we demonstrate that syndecan-1 overexpressed by lungs IPF patients murine models after bleomycin injury....
The respiratory tract surface is protected from inhaled pathogens by a secreted layer of mucus rich in mucin glycoproteins. Abnormal accumulation cardinal feature chronic diseases, but the relationship between and during exacerbations poorly understood. We identified elevations airway 5AC (MUC5AC) MUC5B concentrations spontaneous experimentally induced obstructive pulmonary disease (COPD) exacerbations. MUC5AC was more sensitive to changes expression exacerbation therefore predictably...
In antigen-challenged guinea pigs there is recruitment of eosinophils into the lungs and to airway nerves, decreased function inhibitory M2 muscarinic autoreceptors on parasympathetic nerves in lungs, hyperresponsiveness. A rabbit antibody pig eosinophil major basic protein was used determine whether receptor dysfunction, subsequent hyperresponsiveness, are due antagonism by protein. Guinea were sensitized, challenged with ovalbumin tested 24 h later agonist pilocarpine. Antigen-challenged...
Abstract Phosphatase and tensin homologue deleted from chromosome 10 (Pten) is expressed aberrantly in non–small cell lung cancer cells, but the role of Pten neoplasia has not been fully elucidated. In this study, we used a genetic approach to inactivate bronchial epithelium mice. Although, by itself, inactivation had no discernible effect on epithelial histology, it accelerated tumorigenesis initiated oncogenic K-ras, causing more rapid lethality than that induced K-ras alone (8 weeks...
Since the airways of control mouse lungs contain few alcian blue/periodic acid-Schiff's (AB/PAS)+ staining 'goblet' cells in absence an inflammatory stimulus such as allergen sensitization, it was surprising to find that mice deficient for exocytic priming protein Munc13-2 stain prominently with AB/PAS under conditions. Purinergic agonists (ATP/UTP) stimulated release accumulated mucins Munc13-2-deficient airways, suggesting other airway isoform, Munc13-4, supports agonist-regulated...
Recent studies have demonstrated that K-ras mutations in lung epithelial cells elicit inflammation promotes carcinogenesis mice (intrinsic inflammation). The finding patients with chronic obstructive pulmonary disease (COPD), an inflammatory of the lung, increased risk cancer after controlling for smoking suggests a further link between and extrinsic inflammation. Besides exposure to cigarette smoke, it is thought airway COPD caused by bacterial colonization, particularly non-typeable...