Cell models are instrumental for studying basic and applied aspects of gene and molecular therapy for cystic fibrosis (CF). Human airway epithelial cell cultures maintained at an air-liquid interface and displaying mucociliary differentiation similar to the in vivo epithelium faithfully reproduce high resistance to gene therapy vectors characteristic of the native human mucosa. There cultures facilitate understanding vector interaction with target cells and provide a strong platform for pre-clinical studies vital to the success of gene and molecular therapy for CF. A Tissue Procurement and Cell Culture Core was established at the University of North Carolina (UNC) in 1984, under the auspices of the CF Foundation, to provide standardized cell cultures to CF researchers. The Core has supported UNC Gene Therapy for CF projects since 1993 and has increased its output and capabilities to meet growing research demands. The Core routinely makes available cells and media that are unavailable and/or prohibitively expensive if purchased from commercial suppliers. The Core has focused on providing human airway epithelial cell cultures to UNC CF Center investigators. The present application will support continuing essential services and will increase the range of services to the University -wide gene and molecular therapy community. The Core provides human airway epithelial cells in environments more representative of in vivo conditions, supports relevant in vivo models and supplies additional cell types including progenitor cells. To accomplish these goals, we propose the following specific aims;1) to provide normal and CF human and mouse airway epithelial cells in model systems reproducing important elements of the in vivo airway environment, 2) to cost effectively provide additional lung cell types that are high priority targets for the UNC gene and molecular therapy community, and 3) to cost effectively provide liver and intestine cell types under investigation by the UNC gene and molecular community. Through these functions, and in conjunction with the other Cores in this application, the Cell Models Core will foster collaborations directed at improving vector efficiency to both the airway epithelium and additional cell and organ systems relevant to the research mission of NIDDK.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
5P30DK065988-10
Application #
8448759
Study Section
Special Emphasis Panel (ZDK1-GRB-1)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
10
Fiscal Year
2013
Total Cost
$146,744
Indirect Cost
$47,592
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Sesma, Juliana I; Weitzer, Clarissa D; Livraghi-Butrico, Alessandra et al. (2016) UDP-glucose promotes neutrophil recruitment in the lung. Purinergic Signal 12:627-635
Mitchel, Jennifer A; Antoniak, Silvio; Lee, Joo-Hyeon et al. (2016) IL-13 Augments Compressive Stress-Induced Tissue Factor Expression in Human Airway Epithelial Cells. Am J Respir Cell Mol Biol 54:524-31
Livraghi-Butrico, A; Grubb, B R; Wilkinson, K J et al. (2016) Contribution of mucus concentration and secreted mucins Muc5ac and Muc5b to the pathogenesis of muco-obstructive lung disease. Mucosal Immunol :
Button, Brian; Anderson, Wayne H; Boucher, Richard C (2016) Mucus Hyperconcentration as a Unifying Aspect of the Chronic Bronchitic Phenotype. Ann Am Thorac Soc 13 Suppl 2:S156-62
Cholon, Deborah M; Esther Jr, Charles R; Gentzsch, Martina (2016) Efficacy of lumacaftor-ivacaftor for the treatment of cystic fibrosis patients homozygous for the F508del-CFTR mutation. Expert Rev Precis Med Drug Dev 1:235-243
Yu, Dongfang; Davis, Richard M; Aita, Megumi et al. (2016) Characterization of Rat Meibomian Gland Ion and Fluid Transport. Invest Ophthalmol Vis Sci 57:2328-43
Dang, Hong; Gallins, Paul J; Pace, Rhonda G et al. (2016) Novel variation at chr11p13 associated with cystic fibrosis lung disease severity. Hum Genome Var 3:16020
Menachery, Vineet D; Yount Jr, Boyd L; Sims, Amy C et al. (2016) SARS-like WIV1-CoV poised for human emergence. Proc Natl Acad Sci U S A 113:3048-53
Watson, Michael J; Lee, Shernita L; Marklew, Abigail J et al. (2016) The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Uses its C-Terminus to Regulate the A2B Adenosine Receptor. Sci Rep 6:27390
Blackmon, Richard L; Kreda, Silvia M; Sears, Patrick R et al. (2016) Diffusion-sensitive optical coherence tomography for real-time monitoring of mucus thinning treatments. Proc SPIE Int Soc Opt Eng 9697:

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