Cystic fibrosis investigators within the P30 Center require access to expertise and specialized equipment fortheir studies of CFTR expression and function. For both established CF laboratories and those new to CFresearch, a need has been identified for developing new cell lines expressing mutant and wild type CFTR,and for dedicated equipment and biophysical protocols necessary to assess CFTR function. In particular, wepropose two specific aims:
Specific Aim 1. Cellular models expressing wild type and mutant CFTR will be developed and provided byCore A. These will include primary cells from murine and human lungs, novel lentiviral transduced cell lines,and innovative CF models derived by zinc finger endonuclease modification of the CFTR locus in vitro.
Specific Aim 2. Assistance, equipment and expertise necessary to perform functional assays of CFTR inthe above cell models (Aim 1) will include fluorescent (halide sensitive) dye protocols, Ussing chamberassays and biophysical techniques (patch clamp) necessary to investigate CFTR activity and regulation.The Core will aid in the development/validation of new CF cell models; provide primary murine airwayepithelial cells encoding specific CFTR mutations; and assist investigators with their experiments to test theeffects of AF508 on CFTR protein stability and channel function. Collaborative studies involvingmetabolomic consequences of mutations in CFTR, discovery of peptides from the first cytosolic loop ofCFTR that specifically block NBD1 TMD1 binding and numerous other NIH funded projects will also beassisted by the Core.Core A will foster interdisciplinary research by providing valuable new cell models and assays of CFTRexpression and function to investigators less familiar with the requisite techniques, and contribute toinnovative studies of CF pathogenesis and experimental therapy.
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| Clancy, John Paul; Cotton, Calvin U; Donaldson, Scott H et al. (2018) CFTR modulator theratyping: Current status, gaps and future directions. J Cyst Fibros : |
| Plyler, Z E; Birket, S E; Schultz, B D et al. (2018) Non-obstructive vas deferens and epididymis loss in cystic fibrosis rats. Mech Dev : |
| Poore, T Spencer; Virella-Lowell, Isabel; Guimbellot, Jennifer S (2018) Potential pathogenicity of Inquilinus limosus in a pediatric patient with cystic fibrosis. Pediatr Pulmonol 53:E21-E23 |
| Heltshe, Sonya L; Rowe, Steven M; Skalland, Michelle et al. (2018) Ivacaftor-treated Patients with Cystic Fibrosis Derive Long-Term Benefit Despite No Short-Term Clinical Improvement. Am J Respir Crit Care Med 197:1483-1486 |
| Guimbellot, Jennifer; Solomon, George M; Baines, Arthur et al. (2018) Effectiveness of ivacaftor in cystic fibrosis patients with non-G551D gating mutations. J Cyst Fibros : |
| Cho, Do-Yeon; Lim, Dong-Jin; Mackey, Calvin et al. (2018) Preclinical therapeutic efficacy of the ciprofloxacin-eluting sinus stent for Pseudomonas aeruginosa sinusitis. Int Forum Allergy Rhinol 8:482-489 |
| Raju, S Vamsee; Rowe, Steven M (2018) Not simply the lesser of two evils. Am J Physiol Lung Cell Mol Physiol 314:L236-L238 |
| Peabody, Jacelyn E; Shei, Ren-Jay; Bermingham, Brent M et al. (2018) Seeing cilia: imaging modalities for ciliary motion and clinical connections. Am J Physiol Lung Cell Mol Physiol 314:L909-L921 |
| Davies, Jane C; Moskowitz, Samuel M; Brown, Cynthia et al. (2018) VX-659-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles. N Engl J Med 379:1599-1611 |
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