Cystic fibrosis investigators within the P30 Center require access to expertise and specialized equipment for their studies of CFTR expression and function. For both established CF laboratories and those new to CF research, a need has been identified for developing novel cell lines expressing mutant and wild type CFTR, and for dedicated equipment and biophysical protocols necessary to assess CFTR function. In particular, we propose two specific aims:
Specific Aim 1. Cellular models expressing wild type and mutant CFTR will be developed and provided by Core A. These will include primary cells from murine lungs and novel lentiviral-transduced cell lines. The latter include innovative cell models useful for CFTR proteomic and structural studies and for high throughput screens to discover the next generation of CF drugs.
Specific Aim 2, Assistance, equipment and expertise necessary to perform functional assays of CFTR in the above cell models (Aim 1) will include biophysical techniques (patch clamp). These assays are required to test the efficacies of new maneuvers to rescue mutant CFTR channel activity and regulation as well as to define the underlying mechanisms. The Core will aid in the development/validation of new CF cell models;provide primary murine airway epithelial cells encoding specific CFTR mutations;and assist investigators with their experiments to test the effects of new maneuvers on mutant CFTR (e.g., DeltaF508) protein stability and channel function. Collaborative studies involving proteomic studies of CFTR post-translational modifications, discovery of peptides from the first cytosolic loop of CFTR that specifically block NBD1-TMD1 binding and numerous other NIH funded projects will also be assisted by the Core. Core A will foster interdisciplinary research by providing valuable new cell models and assays of CFTR expression and function to investigators less familiar with the requisite techniques, and contribute to innovative studies of CF pathogenesis and experimental therapy.

Public Health Relevance

Cystic fibrosis (CF) is one of the most common lethal genetic disorders in this country. Currently there are no effective treatment options. This research core provides cell models and functional assays that are essential for testing, validating and refining new CF therapies being developed by P30 investigators.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Center Core Grants (P30)
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Special Emphasis Panel (ZDK1-GRB-7)
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University of Alabama Birmingham
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Heltshe, Sonya L; Rowe, Steven M; Mayer-Hamblett, Nicole (2014) Evaluating the predictive ability of sweat chloride. J Cyst Fibros 13:118
Hill, Aubrey E; Plyler, Zackery E; Tiwari, Hemant et al. (2014) Longevity and plasticity of CFTR provide an argument for noncanonical SNP organization in hominid DNA. PLoS One 9:e109186
Dean, Nichole; Ranganath, Neel K; Jones, Brandon et al. (2014) Porcine nasal epithelial cultures for studies of cystic fibrosis sinusitis. Int Forum Allergy Rhinol 4:565-70
Lee, Seakwoo; Henderson, Mark J; Schiffhauer, Eric et al. (2014) Interference with ubiquitination in CFTR modifies stability of core glycosylated and cell surface pools. Mol Cell Biol 34:2554-65
Oren, Yifat S; McClure, Michelle L; Rowe, Steven M et al. (2014) The unfolded protein response affects readthrough of premature termination codons. EMBO Mol Med 6:685-701
Xue, Xiaojiao; Mutyam, Venkateshwar; Tang, Liping et al. (2014) Synthetic aminoglycosides efficiently suppress cystic fibrosis transmembrane conductance regulator nonsense mutations and are enhanced by ivacaftor. Am J Respir Cell Mol Biol 50:805-16
McClure, Michelle L; Wen, Hui; Fortenberry, James et al. (2014) S-palmitoylation regulates biogenesis of core glycosylated wild-type and F508del CFTR in a post-ER compartment. Biochem J 459:417-25
Zhang, Shaoyan; Ranganath, Neel K; Skinner, Daniel et al. (2014) Marked repression of CFTR mRNA in the transgenic Cftr(tm1kth) mouse model. J Cyst Fibros 13:351-2
Boyle, Michael P; Bell, Scott C; Konstan, Michael W et al. (2014) A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation: a phase 2 randomised controlled trial. Lancet Respir Med 2:527-38
Tuggle, Katherine L; Birket, Susan E; Cui, Xiaoxia et al. (2014) Characterization of defects in ion transport and tissue development in cystic fibrosis transmembrane conductance regulator (CFTR)-knockout rats. PLoS One 9:e91253

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