A5005871186- Cystic Fibrosis Research Advances
- Mycobacterium research and diagnosis
- Neonatal Respiratory Health Research
- Tuberculosis Research and Epidemiology
- Tracheal and airway disorders
- Bacterial biofilms and quorum sensing
- Respiratory viral infections research
- Immune cells in cancer
- Bacterial Genetics and Biotechnology
- Asthma and respiratory diseases
- Immune responses and vaccinations
- Dysphagia Assessment and Management
- Cancer Research and Treatments
- Antibiotic Resistance in Bacteria
- Pediatric health and respiratory diseases
- Pneumocystis jirovecii pneumonia detection and treatment
- Inhalation and Respiratory Drug Delivery
- Bacteriophages and microbial interactions
- Tumors and Oncological Cases
- Cancer therapeutics and mechanisms
- Galectins and Cancer Biology
- Nematode management and characterization studies
- Salmonella and Campylobacter epidemiology
- Infectious Diseases and Mycology
- Fibroblast Growth Factor Research
National Jewish Health
2020-2024
University of Colorado Denver
2020-2024
University of Washington
2011-2023
Cystic Fibrosis Foundation
2023
University of Southern California
2023
Pulmonary and Critical Care Associates
2019
SleepMed
2019
University of Chicago
2016
University of Washington Medical Center
2015
Seattle University
2015
Rationale: Previous work indicates that ivacaftor improves cystic fibrosis transmembrane conductance regulator (CFTR) activity and lung function in people with G551D-CFTR mutations but does not reduce density of bacteria or markers inflammation the airway. These findings raise possibility infection may progress independently CFTR once disease is established.Objectives: To better understand relationship between activity, airway microbiology inflammation, subjects chronic infections.Methods:...
Two mycobacteriophages were administered intravenously to a male with treatment-refractory Mycobacterium abscessus pulmonary infection and severe cystic fibrosis lung disease. The phages engineered enhance their capacity lyse M. selected specifically as the most effective against subject's bacterial isolate. In setting of compassionate use, evidence phage-induced lysis was observed using molecular metabolic assays combined clinical assessments. isolates pre post-phage treatment demonstrated...
In cystic fibrosis (CF) airways, Pseudomonas aeruginosa forms cellular aggregates called biofilms that are thought to contribute chronic infection. To form aggregates, P. can use different mechanisms, each with its own pathogenic implications. However, how they in vivo is controversial and unclear. One mechanism involves a bacterially produced extracellular matrix holds the together. Pel Psl exopolysaccharides structural protective components of this matrix. We develop an immunohistochemical...
ABSTRACT Pseudomonas aeruginosa is an important opportunistic human pathogen that lives in biofilm-like cell aggregates at sites of chronic infection, such as those occur the lungs patients with cystic fibrosis and nonhealing ulcers. During growth a biofilm, P. dramatically increases production filamentous Pf bacteriophage (Pf phage). Previous work indicated when vivo phage was inhibited, less virulent. However, it not clear how abundant quantities similar to produced by biofilms under vitro...
Summary Signature‐tagged transposon mutagenesis of Salmonella with differential recovery from wild‐type and immunodeficient mice revealed that the gene here named cdgR [for c‐diguanylate (c‐diGMP) regulator ] is required for bacterium to resist host phagocyte oxidase in vivo . CdgR consists solely a glutamate‐alanine‐leucine (EAL) domain, predicted cyclic diGMP phosphodiesterase. Disruption decreased bacterial resistance hydrogen peroxide accelerated killing macrophages. An ultrasensitive...
Onset of the adaptive immune response in mice infected with Mycobacterium tuberculosis is accompanied by slowing bacterial replication and establishment a chronic infection. Stabilization numbers during phase infection dependent on activity gamma interferon (IFN-γ)-inducible nitric oxide synthase (NOS2). Previously, we described differential signature-tagged mutagenesis screen designed to identify M. "counterimmune" mechanisms reported isolation three mutants H37Rv strain background...
Chronic pulmonary bacterial infections and associated inflammation remain a cause of morbidity mortality in people with cystic fibrosis (PwCF) despite new modulator therapies. Therapies targeting host factors that dampen detrimental without suppressing immune responses critical for controlling limited, while the development lung caused by antimicrobial resistant bacteria is an increasing global problem, significant challenge CF. Pharmacological compounds mammalian MAPK proteins MEK1 MEK2,...
BACKGROUND. Airflow obstruction is common in cystic fibrosis (CF), yet the underlying pathogenesis remains incompletely understood. People with CF often exhibit airway hyperresponsiveness, transmembrane conductance regulator (CFTR) present smooth muscle (ASM), and ASM from newborn pigs has increased contractile tone, suggesting that loss of CFTR causes a primary defect function. We hypothesized restoring activity would decrease tone people CF.
Limitation of clonal expansion activated T cells is necessary for immune homeostasis, and achieved by growth arrest apoptosis. Growth apoptosis can occur passively secondary to cytokine withdrawal, or be actively induced religation the cell receptor (TCR) in previously proliferating cells. TCR-induced appears require prior arrest, mediated death receptors such as Fas. We tested whether TCR affects responses interleukin (IL)-2, a major survival factor. ligation primary human blocked IL-2...
Chronic airway infection with P. aeruginosa (PA) is a hallmark of cystic fibrosis (CF) disease. The mechanisms producing PA persistence in CF therapies remain poorly understood. To gain insight on physiology patient airways and better understand how vivo bacterial functioning differs from vitro conditions, we investigated the proteomes 35 sputum samples 11 patients. We developed novel bacterial-enrichment method that relies differential centrifugation detergent treatment to enrich for...
CFTR modulators decrease some etiologies of CF airway inflammation; however, data indicate that non-resolving infection and inflammation persist in individuals with chronic bacterial infections. Thus, identification therapies diminish without allowing unrestrained growth remains a critical research goal. Novel strategies for combatting deleterious the modulator era require better understanding cellular contributions to disease, how inflammatory cells change after initiation therapy....
Tuberculosis (TB) is characterized by lifetime persistence of Mycobacterium tuberculosis. Despite the induction a vigorous host immune response that curtails disease progression in majority cases, organism not eliminated. Subsequent immunosuppression can lead to reactivation after prolonged period clinical latency. Thus, while it clear protective mechanisms are engaged during M. tuberculosis infection, also appears pathogen has evolved effective countermechanisms. Genetic studies with animal...
Background: HIV-positive patients at HELP/PSI, Inc, an in-patient drug rehabilitation center, had a high baseline prevalence of Staphylococcus aureus colonization (49%) and incidence infection (17%) in previous year-long study. Methods: A randomized, double-blinded, placebo-controlled study was conducted to determine whether repeated nasal application mupirocin ointment would decrease the odds S. 100 HELP/PSI over 8-month period. 5-day course given monthly, assessed 1 month after each...
<b>This study demonstrates that initiation of the CFTR modulator ivacaftor in people with cystic fibrosis and susceptible <i>CFTR</i> mutations causes an acute reduction blood monocyte sensitivity to key proinflammatory cytokine IFN-γ</b>http://bit.ly/2TeI6LG
Rationale: The etiology of cystic fibrosis (CF) pulmonary exacerbations (PEx) is likely multifactorial with viral, bacterial, and non-infectious pathways contributing. Objectives: To determine whether viral infection status CRP (C-reactive protein) can classify subphenotypes PEx that differ in outcomes biomarker profiles. Methods: Patients were recruited at time admission for a PEx. Nasal swabs sputum samples collected processed using the respiratory panel FilmArray multiplex polymerase...
Mycobacterium abscessus, a species of nontuberculous mycobacteria (NTM), is an opportunistic pathogen that readily cleared by healthy lungs but can cause pulmonary infections in people with chronic airway diseases. Although knowledge pertaining to molecular mechanisms host defense against NTM increasing, macrophage receptors recognize M. abscessus remain poorly defined. Dectin-1, C-type lectin receptor identified as fungal receptor, has been shown be recognition (PRR) for both tuberculosis...
Research to understand the contribution of macrophages nonresolving airway inflammation in cystic fibrosis (CF) and other chronic suppurative airways diseases has been hindered by a lack methods for isolating studying these cells. With development technologies that can characterize small numbers cells or individual cells, there is an even greater need methodologies isolate rare heterogeneous specimens. Here, we describe method overcomes technical obstacles imposed sputum debris apoptotic...