Michael J. Welsh
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View article: Solving Cystic Fibrosis: From lab Bench to Bedside
Solving Cystic Fibrosis: From lab Bench to Bedside Open
Cystic fibrosis (CF) is a serious genetic disease that causes thick, sticky mucus to build up in the lungs and digestive system. For many years, treatments could only manage the symptoms. That began to change with the discovery that CF is …
View article: Molecular prosthetics for CFTR designed for anion selectivity outperform amphotericin B in cultured cystic fibrosis airway epithelia
Molecular prosthetics for CFTR designed for anion selectivity outperform amphotericin B in cultured cystic fibrosis airway epithelia Open
The ion channel-forming natural product amphotericin B (AmB) can serve as a molecular prosthetic for the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel and thereby restore host defenses in cultured cystic fibrosis…
View article: A dose-finding study shows terazosin enhanced energy metabolism in neurologically healthy adults
A dose-finding study shows terazosin enhanced energy metabolism in neurologically healthy adults Open
Background Parkinson's disease (PD) is a common neurodegenerative disease lacking treatments that modify progressive neuron loss. Terazosin (TZ) increases activity of the glycolytic enzyme phosphoglycerate kinase 1 and could potentially be…
View article: Molecular prosthetics and CFTR modulators additively increase secretory HCO<sub>3</sub><sup>−</sup>flux in cystic fibrosis airway epithelia
Molecular prosthetics and CFTR modulators additively increase secretory HCO<sub>3</sub><sup>−</sup>flux in cystic fibrosis airway epithelia Open
Cystic Fibrosis (CF) is caused by loss-of-function mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel predominantly expressed on the apical membrane of epithelial cells. Reduced …
View article: The oxygen level in air directs airway epithelial cell differentiation by controlling mitochondrial citrate export
The oxygen level in air directs airway epithelial cell differentiation by controlling mitochondrial citrate export Open
Oxygen controls most metazoan metabolism, yet in mammals, tissue O 2 levels vary widely. While extensive research has explored cellular responses to hypoxia, understanding how cells respond to physiologically high O 2 levels remains uncert…
View article: Do pulmonary ionocytes absorb chloride or secrete chloride?
Do pulmonary ionocytes absorb chloride or secrete chloride? Open
Pulmonary ionocytes express high levels of cystic fibrosis transmembrane conductance regulator (CFTR) channels. When studied using the short-circuit current technique, ionocytes produce CFTR-dependent short-circuit currents consistent with…
View article: Epithelial responses to CFTR modulators are improved by inflammatory cytokines and impaired by antiinflammatory drugs
Epithelial responses to CFTR modulators are improved by inflammatory cytokines and impaired by antiinflammatory drugs Open
Cystic fibrosis (CF) is a genetic disorder that disrupts CF transmembrane conductance regulator (CFTR) anion channels and impairs airway host defenses. Airway inflammation is ubiquitous in CF, and suppressing it has generally been consider…
View article: Development and Initial Characterization of Pigs with<i>DNAI1</i>Mutations and Primary Ciliary Dyskinesia
Development and Initial Characterization of Pigs with<i>DNAI1</i>Mutations and Primary Ciliary Dyskinesia Open
Mutations in more than 50 different genes cause primary ciliary dyskinesia (PCD) by disrupting the activity of motile cilia that facilitate mucociliary transport (MCT). Knowledge of PCD has come from studies identifying disease-causing mut…
View article: A pilot dose-finding study of Terazosin in humans
A pilot dose-finding study of Terazosin in humans Open
Background Parkinson’s disease (PD) is a prevalent neurodegenerative disorder where progressive neuron loss is driven by impaired brain bioenergetics, particularly mitochondrial dysfunction and disrupted cellular respiration. Terazosin (TZ…
View article: Arteriovenous metabolomics in pigs reveals CFTR regulation of metabolism in multiple organs
Arteriovenous metabolomics in pigs reveals CFTR regulation of metabolism in multiple organs Open
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), a multiorgan disease that is characterized by diverse metabolic defects. However, other than specific CFTR mutations, the factors …
View article: Mitochondrial uncoupling proteins protect human airway epithelial ciliated cells from oxidative damage
Mitochondrial uncoupling proteins protect human airway epithelial ciliated cells from oxidative damage Open
Apical cilia on epithelial cells defend the lung by propelling pathogens and particulates out of the respiratory airways. Ciliated cells produce ATP that powers cilia beating by densely grouping mitochondria just beneath the apical membran…
View article: A model for stimulation of enzyme activity by a competitive inhibitor based on the interaction of terazosin and phosphoglycerate kinase 1
A model for stimulation of enzyme activity by a competitive inhibitor based on the interaction of terazosin and phosphoglycerate kinase 1 Open
The drug terazosin (TZ) binds to and can enhance the activity of the glycolytic enzyme phosphoglycerate kinase 1 (PGK1) and can increase ATP levels. That finding prompted studies of TZ in Parkinson’s disease (PD) in which decreased neurona…
View article: CFTR-rich ionocytes mediate chloride absorption across airway epithelia
CFTR-rich ionocytes mediate chloride absorption across airway epithelia Open
The volume and composition of a thin layer of liquid covering the airway surface defend the lung from inhaled pathogens and debris. Airway epithelia secrete Cl- into the airway surface liquid through cystic fibrosis transmembrane conductan…
View article: Inflammation as a Regulator of the Airway Surface Liquid pH in Cystic Fibrosis
Inflammation as a Regulator of the Airway Surface Liquid pH in Cystic Fibrosis Open
The airway surface liquid (ASL) is a thin sheet of fluid that covers the luminal aspect of the airway epithelium. The ASL is a site of several first-line host defenses, and its composition is a key factor that determines respiratory fitnes…
View article: Using Administrative Data to Impute Income Non-Response in Household Surveys
Using Administrative Data to Impute Income Non-Response in Household Surveys Open
Income is simultaneously one of the most important variables used by economists and the variable most likely to be missing due to item non-response.While observations that are missing income responses are often dropped from analyses, such …
View article: Use of Glycolysis‐Enhancing Drugs and Risk of Parkinson's Disease
Use of Glycolysis‐Enhancing Drugs and Risk of Parkinson's Disease Open
Background Terazosin (TZ) and closely related α1‐adrenergic receptor antagonists (doxazosin [DZ] and alfuzosin [AZ]) enhance glycolysis and reduce neurodegeneration in animal models. Observational evidence in humans from several databases …
View article: WNK Inhibition Increases Surface Liquid pH and Host Defense in Cystic Fibrosis Airway Epithelia
WNK Inhibition Increases Surface Liquid pH and Host Defense in Cystic Fibrosis Airway Epithelia Open
In cystic fibrosis (CF), reduced HCO3- secretion acidifies the airway surface liquid (ASL), and the acidic pH disrupts host defenses. Thus, understanding the control of ASL pH (pHASL) in CF may help identify novel targets and facilitate th…
View article: Use of glycolysis enhancing drugs has less risk of Parkinson’s disease than 5α-reductase inhibitors
Use of glycolysis enhancing drugs has less risk of Parkinson’s disease than 5α-reductase inhibitors Open
Background Terazosin and closely related α1-adrenergic receptor antagonists (doxazosin and alfuzosin; TZ/DZ/AZ) enhance glycolysis and reduce neurodeneration in animal models. Observational evidence in humans from several databases support…
View article: Elastic mucus strands impair mucociliary clearance in cystic fibrosis pigs
Elastic mucus strands impair mucociliary clearance in cystic fibrosis pigs Open
Significance In many lung diseases, increased amounts of and/or abnormal mucus impair mucociliary clearance, a key defense against inhaled and aspirated material. Submucosal glands lining cartilaginous airways secrete mucus strands that ar…
View article: Combining Ivacaftor and Intensive Antibiotics Achieves Limited Clearance of Cystic Fibrosis Infections
Combining Ivacaftor and Intensive Antibiotics Achieves Limited Clearance of Cystic Fibrosis Infections Open
Recent work shows that people with cystic fibrosis (CF) and chronic lung infections generally remain persistently infected after treatment with drugs that target the CF physiological defect (called CFTR modulators). However, changes produc…