A5018129118- Cystic Fibrosis Research Advances
- Neonatal Respiratory Health Research
- Prostate Cancer Treatment and Research
- Prostate Cancer Diagnosis and Treatment
- Gut microbiota and health
- Tracheal and airway disorders
- Cancer Genomics and Diagnostics
- Asthma and respiratory diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Inhalation and Respiratory Drug Delivery
- Genomics and Phylogenetic Studies
- Microbial Community Ecology and Physiology
- Respiratory Support and Mechanisms
- Colorectal Cancer Screening and Detection
- Genetic and Kidney Cyst Diseases
- Pediatric Hepatobiliary Diseases and Treatments
- Infant Nutrition and Health
- Bladder and Urothelial Cancer Treatments
- Cancer Immunotherapy and Biomarkers
- Protein Kinase Regulation and GTPase Signaling
- Congenital Ear and Nasal Anomalies
- Parasitic infections in humans and animals
- Hedgehog Signaling Pathway Studies
- Intestinal Malrotation and Obstruction Disorders
- Advanced Drug Delivery Systems
University of Iowa
2011-2024
Johns Hopkins Medicine
2018-2024
University of Baltimore
2018-2024
Johns Hopkins University
2018-2024
Howard Hughes Medical Institute
2014-2024
Towson University
2018-2021
University Hospital of Basel
2011
University Hospital Cologne
1998
University of Cologne
1998
Airway infections put to an acid test Most people with cystic fibrosis suffer from chronic respiratory infections. The mechanistic link between this symptom and the genetic cause of disease (mutations that compromise function transmembrane conductance regulator, CFTR) is not fully understood. Studying animal models, Shah et al. find in absence functional CFTR, surface liquid airways becomes acidic, which impairs host defenses against infection. This acidification occurs through action a...
Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the gene encoding cystic transmembrane conductance regulator (CFTR) anion channel. The most common CF-associated mutation ΔF508, which deletes a phenylalanine position 508. In vitro studies indicate that resultant protein, CFTR-ΔF508, misprocessed, although vivo consequences of this remain uncertain. To better understand effects ΔF508 vivo, we produced CFTR(ΔF508/ΔF508) pigs. Our biochemical, immunocytochemical,...
Loss of cystic fibrosis transmembrane conductance regulator (CFTR) anion channel function causes (CF) lung disease. CFTR is expressed in airway epithelia, but how CF alters electrolyte transport across epithelia has remained uncertain. Recent studies a porcine model showed that vivo, excised, and cultured −/− ΔF508/ΔF508 lacked conductance, they did not hyperabsorb Na + . Therefore, we asked whether Cl − conductances were altered human epithelia. We studied differentiated primary cultures...
Diabetes mellitus predisposes the host to bacterial infections. Moreover, hyperglycemia has been shown be an independent risk factor for respiratory The luminal surface of airway epithelia is covered by a thin layer liquid (ASL) and normally sterile despite constant exposure bacteria. balance between growth killing in determines outcome inhaled or aspirated bacteria: infection sterility. We hypothesized that restriction carbon sources –including glucose– ASL required sterility lungs. found...
Cystic fibrosis (CF) pigs develop disease with features remarkably similar to those in people CF, including exocrine pancreatic destruction, focal biliary cirrhosis, micro-gallbladder, vas deferens loss, airway disease, and meconium ileus. Whereas ileus occurs 15% of babies the penetrance is 100% newborn CF pigs. We hypothesized that transgenic expression porcine transmembrane conductance regulator (pCFTR) cDNA under control intestinal fatty acid-binding protein (iFABP) promoter would...
It is well known that the gastrointestinal (GI) microbiota can influence metabolism, pharmacokinetics, and toxicity of cancer therapies. Conversely, effect treatments on composition GI poorly understood. We hypothesized oral androgen receptor axis-targeted therapies (ATT), including bicalutamide, enzalutamide, abiraterone acetate, may be associated with compositional differences in microbiota. profiled fecal a cross-sectional study 30 patients included healthy male volunteers men different...
Cystic fibrosis (CF) is caused by mutations in the gene encoding cystic transmembrane conductance regulator (CFTR) anion channel. Airway disease major source of morbidity and mortality. Successful implementation gene- cell-based therapies for CF airway requires knowledge relationships among percentages targeted cells, levels CFTR expression, correction electrolyte transport, rescue host defense defects. Previous studies suggested that, when ∼10-50% epithelial cells expressed CFTR, they...
Recent studies in cancer patients and animal models demonstrate that intestinal microbiota influence the therapeutic efficacy of treatments, including immune checkpoint inhibition. However, no to-date have investigated relationships between gastrointestinal composition response to inhibition advanced metastatic castrate resistant prostate (mCRPC). We performed 16S rRNA gene sequencing fecal DNA from 23 individuals with mCRPC progressing on enzalutamide just prior treatment anti-PD-1...
Abstract Objectives/Hypothesis: Chronic sinusitis is nearly universal in humans with cystic fibrosis (CF) and accompanied by sinus hypoplasia (small sinuses). However, whether impaired development a primary feature of loss the transmembrane conductance regulator (CFTR) or secondary consequence chronic infection remains unknown. Our objective was to study early pathogenesis disease CF. Study Design: Animal/basic science research. Methods: Sinus studied porcine CF model. Results: Porcine...
Intestinal current measurements (ICM) from rectal biopsies are a sensitive means to detect cystic fibrosis transmembrane conductance regulator (CFTR) function, but have not been optimized for multicenter use. We piloted standard operating procedures (SOPs) CFTR activity by ICM and examined key questions use in clinical trials. SOPs using human were developed across three centers used characterize ion transport non-CF CF subjects (two severe mutations). All data centrally evaluated blinded...
Abstract The number of small proteins (SPs) encoded in the Escherichia coli genome is unknown, as current bioinformatics and biochemical techniques make short gene protein identification challenging. One method involves adding an epitope tag to 3′ end a open reading frame (sORF) on chromosome, with synthesis confirmed by immunoblot assays. In this study, strategy was used identify new E. proteins, tagging 80 sORFs genome, assayed for synthesis. selected represent diverse sequence...
Significance Prostate infections and inflammation are potential initiating factors in prostate cancer development. Here, we investigated whether bacterial associated with the presence of most common oncogenic gene fusion, TMPRSS2:ERG, early precursor lesions. We provide evidence that TMPRSS2:ERG (ERG+) fusions can initiate risk factor lesions, including proliferative inflammatory atrophy setting infection. further demonstrate these infection-associated ERG+ lesions transitioning to invasive...
Short read 16 S rRNA amplicon sequencing is a common technique used in microbiome research. However, inaccuracies estimated bacterial community composition can occur due to amplification bias of the targeted hypervariable region. A potential solution sequence and assess multiple regions tandem, yet there currently no consensus as appropriate method for analyzing this data. Additionally, are many analysis resources data produced from Illumina platform, but fewer open-source options available...
The drug terazosin (TZ) binds to and can enhance the activity of glycolytic enzyme phosphoglycerate kinase 1 (PGK1) increase ATP levels. That finding prompted studies TZ in Parkinson’s disease (PD) which decreased neuronal energy metabolism is a hallmark feature. was neuroprotective cell-based animal PD models large epidemiological humans. However, how might PGK1 has remained perplexing question because structural data revealed that site binding overlaps with substrate binding, predicting...
Gene fusions are hybrid genes that arise from chromosomal rearrangements linking two independent genes. The most common gene fusion in prostate cancer involves the 5′ androgen-regulated TMPRSS2 promoter fused with 3′ ETS transcription factor ERG. TMPRSS2:ERG (T:E) occur about half of all cancers and considered an early event oncogenesis. Investigations into mechanism behind T:E initiation using vitro systems hindered by technical limitations posed fluorescence situ hybridization suboptimal...
Background Chronic sinusitis is universal in cystic fibrosis (CF) and our current treatments are ineffective reversing sinus disease. The objective of this work was to determine if increasing CF transmembrane conductance regulator (CFTR) activity by ivacaftor could treat disease assess its effect on primary epithelial cultures. Methods Case report 1 patient with long‐standing chronic a new diagnosis mild mutation (P205S) severe (G551D). We discuss clinical changes symptoms, radiographic...
Significance Previous studies localized the hedgehog (HH) signaling system to primary cilia. We discovered that motile cilia on airway epithelia also contain HH proteins, indicating like cilia, these have an important sensory function. However, in contrast function of most sonic (SHH) elicits noncanonical signaling, reducing cellular levels cAMP. These findings suggest SHH may quiet defenses. Involvement lung disease and positioning where they sample other ligands lumen might modulate...
Abstract We aim to understand, from acquired genetic alterations in tumors, why African American (AA) men are more likely develop aggressive prostate cancer. By analyzing somatic mutations 39 genes using deeper next-generation sequencing with an average depth of 2,522 reads for tumor DNA and genome-wide copy-number (CNA) cancer a total 171 AA/black comparing those 860 European (EA)/white men, we here present several novel findings. First, >35% AA harbor damaging APC, ATM, BRCA2,...
Selenoproteins play important roles in many cellular functions and biochemical pathways mammals. Our previous study showed that the deficiency of 15 kDa selenoprotein (
A balance between alveolar liquid absorption and secretion is critical for maintaining optimal subphase height facilitating gas exchange in the space. However, role of cystic fibrosis transmembrane regulator protein (CFTR) this homeostatic process has remained elusive. Using a newly developed porcine model fibrosis, which CFTR absent, we investigated ion transport properties isolated type II epithelial cells (T2AECs) cultured at air-liquid interface. was distributed exclusively to apical...
Parkinson's disease (PD) is a prevalent neurodegenerative disorder where progressive neuron loss driven by impaired brain bioenergetics, particularly mitochondrial dysfunction and disrupted cellular respiration. Terazosin (TZ), an α-1 adrenergic receptor antagonist with known efficacy in treating benign prostatic hypertrophy hypertension, has shown potential addressing energy metabolism deficits associated PD due to its action on phosphoglycerate kinase 1 (PGK1). This study aimed investigate...