A5002667632- Cystic Fibrosis Research Advances
- Bacterial biofilms and quorum sensing
- Sinusitis and nasal conditions
- Inhalation and Respiratory Drug Delivery
- Antibiotic Resistance in Bacteria
- Neonatal Respiratory Health Research
- Asthma and respiratory diseases
- Head and Neck Surgical Oncology
- Antimicrobial Peptides and Activities
- Wnt/β-catenin signaling in development and cancer
- Mycobacterium research and diagnosis
- Evolution and Genetic Dynamics
- Nasal Surgery and Airway Studies
- Bacterial Genetics and Biotechnology
- Pediatric health and respiratory diseases
- Vibrio bacteria research studies
- Pancreatitis Pathology and Treatment
- Drug-Induced Adverse Reactions
- Electronic Health Records Systems
- Nanoplatforms for cancer theranostics
- Cancer Cells and Metastasis
- Dermatological and COVID-19 studies
- Plant Pathogenic Bacteria Studies
- COVID-19 Clinical Research Studies
- EEG and Brain-Computer Interfaces
University of Pittsburgh
2014-2025
University of Pittsburgh Medical Center
2023-2024
Pulmonary and Allergy Associates
2024
Rush University Medical Center
2021
Durham University
2008
University of Washington
2003
BackgroundMany individuals with cystic fibrosis (CF) have chronic rhinosinusitis resulting in nasal obstruction, sinus infections, and repeated surgeries. Elexacaftor-tezacaftor-ivacaftor is a highly effective modulator therapy approved for aged 6 years or older CF who at least one F508del allele other responsive mutation. The current study tests the hypothesis that ELX/TEZ/IVA improves sinonasal disease CF.MethodsThe was pre/post, observational cohort conducted two sites. Participants...
Abstract Background While the widespread initiation of elexacaftor/tezacaftor/ivacaftor (ETI) has led to dramatic clinical improvements among persons with cystic fibrosis (pwCF), little is known about how ETI affects respiratory mucosal inflammatory and physiochemical environment, or these changes relate lung function. Methods We performed a prospective, longitudinal study adults CF chronic rhinosinusitis (CF‐CRS) followed at our center ( n = 18). Endoscopic upper tract (paranasal sinus)...
Today, more than 90% of people with cystic fibrosis (pwCF) are eligible for the highly effective transmembrane conductance regulator (CFTR) modulator therapy called elexacaftor/tezacaftor/ivacaftor (ETI) and its use is widespread. Given drastic respiratory symptom improvement experienced by many post-ETI, clinical studies already underway to reduce number therapies, including antibiotic regimens, that pwCF historically relied on combat lung disease progression. Early suggest bacterial burden...
Background and Purpose— The present study hypothesized that side of stroke level recovery influence motor system organization after stroke. Methods— Functional MRI was performed on 14 control subjects 21 patients with chronic during index finger tapping (control subjects, right; patients, recovered side). Results— On functional MRI, right arm involvement showed (1) significantly smaller activation in contralateral cortexes compared subjects; (2) ipsilateral (nonstroke) premotor larger...
Abstract Maintenance of classic stem cell hierarchies is dependent upon self-renewal mediated in part by Wnt/β-catenin regulation the cycle. This function critical rapidly renewing tissues due to obligate role played tissue cell. However, hierarchy responsible for maintenance conducting airway epithelium distinct from hierarchies. The airways maintained transit-amplifying cells steady state; rare bronchiolar are activated participate epithelial repair only following depletion cells. Here, we...
ABSTRACT Background Severe chronic rhinosinusitis (CRS) is a near universal manifestation of cystic fibrosis. Elexacaftor/tezacaftor/ivacaftor (ETI) an oral, small molecule, highly effective Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) corrector–potentiator drug. In people with fibrosis age > 12 years, ETI improves sinonasal symptoms, endoscopy findings, polyp size, and radiologic findings. This study evaluates changes in CRS children ages 6–12 years newly started on ETI....
Bronchiolar Clara cells undergo phenotypic changes during development and in disease. These are poorly described due to a paucity of molecular markers. We used chemical transgenic approaches ablate cells, allowing identification their unique gene expression profile. Flavin monooxygenase 3 (Fmo3), paraoxonase 1 (Pon1), aldehyde oxidase (Aox3), claudin 10 (Cldn10) were identified as novel cell New existing marker genes categorized into three classes based on developmental pattern. Cldn10 was...
Signaling by Wnt/beta-catenin regulates self-renewal of tissue stem cells in the gut and, when activated embryonic bronchiolar epithelium, leads to cell expansion. We have used transgenic and type-specific knockout strategies determine roles for beta-catenin-regulated gene expression normal maintenance repair epithelium. Analysis TOPGal transgene activity detected beta-catenin signaling steady-state repairing However, broad distribution phenotype precluded establishment a clear role or...
Background Chronic rhinosinusitis (CRS) is a significant manifestation of cystic fibrosis (CF) with wide‐ranging symptom and disease severity. The goal the study was to determine clinical variables that correlate outcome measures Methods A prospective, longitudinal, observational 33 adults symptomatic CRS treated in CF‐focused otolaryngology clinic performed. Symptom severity, presence exacerbations, endoscopic appearance were assessed, regression analysis used predictors outcome. Results...
Pseudomonas aeruginosa notoriously adapts to the airways of people with cystic fibrosis (CF), yet how infection-site biogeography and associated evolutionary processes vary as lifelong infections progress remains unclear. Here we test hypothesis that early adaptations promoting aggregation influence evolutionary-genetic trajectories by examining longitudinal P. from sinuses six adults CF. Highly host-adapted lineages harbored mutator genotypes displaying signatures genome degradation recent...
The cystic fibrosis (CF) respiratory tract harbors pathogenic bacteria that cause life-threatening chronic infections. Of these, Pseudomonas aeruginosa becomes increasingly dominant with age and is associated worsening lung function declining microbial diversity. We aimed to understand why P. dominates over other pathogens disease. Here, we show responds dynamic changes in iron concentration, often viral infection pulmonary exacerbations, become more competitive via expression of the TseT...
Objectives The 22‐question SinoNasal Outcome Test (SNOT‐22) assesses chronic rhinosinusitis (CRS) severity. We aimed to identify predictors of SNOT‐22 score improvement following highly effective modulator therapy (HEMT) initiation and corroborate the minimal clinically important difference (MCID) in adults with cystic fibrosis (CF). Methods Prospective observational data was pooled from four studies across 10 US centers investigating people CF (PwCF) CRS. Three evaluated HEMT's impact on...
Defective epithelial repair in the setting of chronic lung disease has been suggested to contribute uncontrolled extracellular matrix (ECM) deposition and development fibrosis. We sought directly test this hypothesis through gene expression profiling total RNA isolated from mouse models selective cell injury that are associated with either productive or abortive repair. Analysis repairing lungs naphthalene-exposed mice revealed prominent clusters up-regulated genes putative roles regulation...
Pseudomonas aeruginosa is an opportunistic human pathogen with a complex respiratory chain. The bacterium predicted to express three NADH:ubiquinone oxidoreductases (NDH-1, NDH-2 and Nqr). We created deletions strains of the alone, in combination determine respective roles NADH dehydrogenases growth virulence. NDH-1 were largely redundant under aerobic conditions. Aerobic dehydrogenase enzymatic activity assay was lost deletion both NDH-2. Under anaerobic conditions, required for robust...
Chronic rhinosinusitis (CRS) is a common, yet underreported and understudied manifestation of upper respiratory disease in people with cystic fibrosis (CF). Recently developed standard care guidelines for the management CF CRS suggest treatment airway may ameliorate lower disease. We sought to determine whether changes sinus microbial community diversity specific taxa known cause lung are associated increased inflammation. performed 16S rRNA gene sequencing, supplemented cytokine analyses,...
Mucosa-associated biofilms are associated with many human disease states, but the host mechanisms promoting biofilm remain unclear. In chronic respiratory diseases like cystic fibrosis (CF), Pseudomonas aeruginosa establishes infection through formation. P . can be attracted to interspecies potassium currents emanating from biofilms. We hypothesized that could, similarly, sense and respond efflux airway epithelial cells (AECs) promote biofilm. Using co-culture imaging assays of grown in...
Pseudomonas aeruginosa grows in highly antibiotic-tolerant biofilms during chronic airway infections. Dispersal of bacteria from may restore antibiotic susceptibility or improve host clearance. We describe models to study biofilm dispersal the nutritionally complex environment human airway. P. was cocultured apical surface epithelial cells (AECs) a perfusion chamber. Dispersal, triggered by sodium nitrite, nitric oxide (NO) donor, tracked live cell microscopy. Next, static model developed...
Abstract Background Chronic rhinosinusitis (CRS) is common in individuals with cystic fibrosis (CF) and marked by chronic inflammation episodes of infection that negatively impact quality life. Several studies have shown elexacaftor–tezacaftor–ivacaftor (ETI) improves symptoms examination findings CF‐CRS. The current study determines the effect ETI on sinonasal microbiota CF. Methods Sinonasal samples were collected under endoscopic visualization before after starting ETI. Samples subjected...
Sodium nitrite has broad antimicrobial activity at pH 6.5, including the ability to prevent biofilm growth by Pseudomonas aeruginosa on surfaces of airway epithelial cells. Because its activity, is being investigated as an inhaled agent for chronic P. infections in cystic fibrosis patients. However, interaction between and commonly used aminoglycosides unknown. This paper investigates tobramycin liquid culture, abiotic biofilms, a biotic model simulating conditions airway. The addition...
The ubiquitous involvement of key iron-containing metalloenzymes in metabolism is reflected the dependence virtually all bacteria on iron for growth and, thereby, potentially provides multiple biomolecular targets antimicrobial killing. We hypothesized that nitrosative stress, which induces damage to metalloproteins, would sensitize ferric mimic gallium(III) (Ga3+), providing a novel therapeutic combination. Using both laboratory and clinical isolates Pseudomonas aeruginosa, we herein...
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Sodium nitrite inhibits bacterial respiration and is in development as an antimicrobial for chronic infections associated with cystic fibrosis. The goal of the current study was to investigate interaction between ciprofloxacin. Using liquid culture killing assays a biotic biofilm model, we observed that induces tolerance
grows as a biofilm under many environmental conditions, and the bacterium can disperse from biofilms via highly regulated, dynamic processes. However, physiologic triggers of dispersal remain poorly understood. Based on prior literature describing triggered by forms starvation, we tested bacterial respiratory inhibitors for in two models resembling chronic airway infections. Our underlying hypothesis was that could serve model downstream effects starvation. We used experimental conditions....