A5060336450- Cystic Fibrosis Research Advances
- Soybean genetics and cultivation
- Legume Nitrogen Fixing Symbiosis
- Bacterial biofilms and quorum sensing
- Respiratory viral infections research
- Antibiotic Resistance in Bacteria
- Neonatal Respiratory Health Research
- Antimicrobial Peptides and Activities
- Pediatric health and respiratory diseases
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Bacterial Infections and Vaccines
- Inhalation and Respiratory Drug Delivery
- Genomics and Phylogenetic Studies
- Retinoids in leukemia and cellular processes
- Sinusitis and nasal conditions
- Pneumonia and Respiratory Infections
- Extracellular vesicles in disease
- Vibrio bacteria research studies
- Pneumocystis jirovecii pneumonia detection and treatment
- Asthma and respiratory diseases
- Gut microbiota and health
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Receptor Mechanisms and Signaling
University of Pittsburgh
2015-2024
Dartmouth College
2007-2024
Stanford University
2023
Medscape
2023
Baylor College of Medicine
2023
American College of Medical Genetics
2023
University of Iowa
2023
Pittsburg State University
2021
Michigan State University
2003-2012
C3J Therapeutics (United States)
2012
Transforming growth factor beta1 (TGF-beta1) is a potent fibrotic responsible for the synthesis of extracellular matrix. TGF-beta1 acts through TGF-beta type I and II receptors to activate intracellular mediators, such as Smad proteins, p38 mitogen-activated protein kinase (MAPK), signal-regulated pathway. We expressed domain receptor [activin receptor-like (ALK)5] substrate, Smad3, determined that SB-431542 selective inhibitor Smad3 phosphorylation with an IC50 94 nM. It inhibited...
Bacteria use a variety of secreted virulence factors to manipulate host cells, thereby causing significant morbidity and mortality. We report mechanism for the long-distance delivery multiple bacterial factors, simultaneously directly into cell cytoplasm, thus obviating need direct interaction pathogen with cause cytotoxicity. show that outer membrane–derived vesicles (OMV) by opportunistic human Pseudomonas aeruginosa deliver including β-lactamase, alkaline phosphatase, hemolytic...
Ferroptosis is a death program executed via selective oxidation of arachidonic acid–phosphatidylethanolamines (AA-PE) by 15-lipoxygenases. In mammalian cells and tissues, ferroptosis has been pathogenically associated with brain, kidney, liver injury/diseases. We discovered that prokaryotic bacterium, Pseudomonas aeruginosa, does not contain AA-PE can express lipoxygenase (pLoxA), oxidize host to 15-hydroperoxy-AA-PE (15-HOO-AA-PE), trigger in human bronchial epithelial cells. Induction...
Enhanced antibiotic resistance of Pseudomonas aeruginosa in the cystic fibrosis (CF) lung is thought to be due formation biofilms. However, there no information on P. biofilms grown human airway epithelial cells or effects biofilm by aeruginosa. Thus we developed a coculture model and report that increase tobramycin (Tb) >25-fold compared with abiotic surfaces. Therefore, concentration Tb required kill 10-fold higher than achievable lungs CF patients. In addition, expressing DeltaF508-CFTR...
Clinical observations link respiratory virus infection and Pseudomonas aeruginosa colonization in chronic lung disease, including cystic fibrosis (CF) obstructive pulmonary disease. The development of P. into highly antibiotic-resistant biofilm communities promotes airway accounts for disease progression patients. Although clinical studies show a strong correlation between CF patients' acquisition infections infection, little is known about the mechanism by which are initiated host. Using...
Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen chronically infecting the lungs of patients with chronic obstructive pulmonary disease (COPD), pneumonia, cystic fibrosis (CF), and bronchiectasis. Cif (PA2934), a bacterial toxin secreted in outer membrane vesicles (OMV) by P. aeruginosa, reduces CFTR-mediated chloride secretion human airway epithelial cells, key driving force for mucociliary clearance. The aim this study was to investigate mechanism whereby secretion....
Laboratory models have become a cornerstone of modern microbiology. However, the accuracy even most commonly used has never been evaluated. Here, we propose quantitative framework based on gene expression data to evaluate model performance and apply it Pseudomonas aeruginosa cystic fibrosis lung infection. We discovered that these captured different aspects P. infection physiology, identify which functional categories are not by each model. These methods will provide researchers with solid...
Laboratory models are critical to basic and translational microbiology research. Models serve multiple purposes, from providing tractable systems study cell biology allowing the investigation of inaccessible clinical environmental ecosystems. Although there is a recognized need for improved model systems, gap in rational approaches accomplish this goal. We recently developed framework assessing accuracy microbial by quantifying how closely each gene expressed natural environment various...
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...
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)...
ABSTRACT We previously reported that Pseudomonas aeruginosa PA14 secretes a protein can reduce the apical membrane expression of c ystic f ibrosis t ransmembrane conductance r egulator (CFTR) protein. Here we report have used proteomic approach to identify this secreted as PA2394, and named gene cif , for C FTR i nhibitory actor. demonstrate Cif is found associated with outer membrane-derived vesicles. Expression in Escherichia coli purification C-terminal six-His-tagged showed necessary...
The cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ABC transporter superfamily, is cyclic AMP-regulated chloride channel and other ion channels transporters. In epithelial cells CFTR rapidly endocytosed from apical plasma membrane efficiently recycles back to membrane. Because ubiquitination targets for degradation in lysosome, deubiquitinating enzymes (DUBs) are likely facilitate recycling. Accordingly, aim this study was identify DUBs that regulate...
Epithelial host defense proteins comprise a critical component of the pulmonary innate immune response to infection. The short palate, lung, nasal epithelium clone (PLUNC) 1 (SPLUNC1) protein is member bactericidal/permeability-increasing (BPI) fold-containing (BPIF) family, sharing structural similarities with BPI-like proteins. SPLUNC1 25 kDa secretory that expressed in nasal, oropharyngeal, and lung epithelia, has been implicated airway against Pseudomonas aeruginosa other organisms....
A major challenge in microbial biofilm control is biocide resistance. Phenotypic adaptations and physical protective effects have been historically thought to be the primary mechanisms for glutaraldehyde resistance bacterial biofilms. Recent studies indicate presence of genetic resistance, but very little known about contributory factors. Here, we demonstrate that efflux pumps contribute Pseudomonas fluorescens aeruginosa The RNA-seq data show phosphonate degradation, lipid biosynthesis,...
Significance Pseudomonas aeruginosa pulmonary infections cause prolonged and destructive inflammation for cystic fibrosis patients. Despite vigorous neutrophilic responses, P. persists in a chronic hyperinflammatory environment. We show that the virulence factor, transmembrane conductance regulator inhibitory factor (Cif), promotes sustained airway by reducing host pro-resolving lipid mediators. Cif hydrolyzes epithelial-derived 14,15-epoxyeicosatrienoic acid, disrupting transcellular...
Phage therapy is a therapeutic approach to treat multidrug-resistant (MDR) infections that employs lytic bacteriophages (phages) eliminate bacteria. Despite the abundant evidence for its success as an antimicrobial in Eastern Europe, there scarce data regarding effects on human host. Here, we aimed understand how phages interact with cells of airway epithelium, tissue site colonized by bacterial biofilms numerous chronic respiratory disorders. Using panel Pseudomonas aeruginosa and...
RAMPs (1McLatchie L.M. Fraser N.J. Main M.J. Wise A. Brown J. Thompson N. Solari R. Lee M.G. Foord S.M. Nature. 1998; 393: 333-339Crossref PubMed Scopus (1868) Google Scholar–3Kamitani S. Asakawa M. Shimekake Y. Kuwasako K. Nakahara Sakata T. FEBS Lett. 1999; 448: 111-114Crossref (112) Scholar) are single transmembrane accessory proteins crucial for plasma membrane expression, which also determine receptor phenotype of various G-protein-coupled receptors. For example, adrenomedullin...
Chronic infections with the opportunistic pathogen Pseudomonas aeruginosa are responsible for majority of morbidity and mortality in patients cystic fibrosis (CF). While P. may initially be treated successfully standard antibiotics, chronic typically arise as bacteria transition to a biofilm mode growth acquire remarkable antimicrobial resistance. To address critical need novel therapeutics that can effectively suppress bacterial challenging physiological environments, such CF lung, we have...
A recent workshop titled "Developing Models to Study Polymicrobial Infections," sponsored by the Dartmouth Cystic Fibrosis Center (DartCF), explored development of new models study polymicrobial infections associated with airways persons cystic fibrosis (CF). The gathered 35+ investigators over two virtual sessions. Here, we present findings this workshop, summarize some challenges involved developing such models, and suggest three frameworks tackle complex problem. proposed here, believe,...
Pseudomonas aeruginosa infections can be difficult to treat and new therapeutics are needed. Bacteriophage therapy is a promising alternative traditional antibiotics, but large numbers of isolated characterized phages lacking. We collected 23 diverse P. isolates from people with cystic fibrosis (CF) clinical infections, used them screen isolate over dozen aeruginosa-targeting hospital wastewater. Phages were genome sequencing, comparative genomics, lytic activity screening against all...
Laboratory models are central to microbiology research, advancing the understanding of bacterial physiology by mimicking natural environments, from soil human microbiome. When studying host–bacteria interactions, animal enable investigators examine dynamics associated with a host, and in case infections, necessary translate basic research into clinical treatments. Efforts toward improving infection typically based on reproducing host genotypes/phenotypes disease manifestations, leaving gap...