Basic pharmacological research aimed at identifying drugs that may correct the cellular derangements that lead to the debilitating and often fatal lung disease associated with cystic fibrosis requires a continuing and dependable source of cystic fibrosis and """"""""normal"""""""" respiratory tissues. Cell culture techniques that allow the propagation of respiratory epithelial cells and formation of differentiated cell culture model systems provide a necessary and powerful tool for testing candidate drugs. Thus, the primary objective of the Cell Models Core is the collection of CF and non-CF respiratory tract tissues and the preparation of differentiated cultures of the respiratory surface epithelial cells and the tracheobronchial submucosal gland cells. A secondary objective of the Cell Models Core is to identify cell culture conditions that permit full expression of differentiated cellular functions, particularly in cell cultures that have been expanded by serial propagation. A tissue procurement system has been established for obtaining both CF and control nasal and airway tissues. Procured tissue is enzymatically digested, and liberated surface epithelial and submucosal gland acinar cells are established as cell cultures. The surface epithelial cells are studied as primary cell cultures of highly differentiated cell sheets that mimic the structure and function of the native nasal and airway epithelium. To increase the number of cell sheets available for screening compounds, some cell cultures are also expanded by serial propagation. The initial primary cultures of the tracheobronchial gland cells are expanded and then seeded as secondary cultures for experimental use. The conditions in which the passaged gland cells are grown are manipulated to produce cells expressing either a mucous or serous cell phenotype. Having respiratory epithelial cells derived from both the mucosal surface and the submucosal gland cells allows investigators to test candidate drugs for action in the various respiratory tract cells most affected in cystic fibrosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
1P30DK072517-01
Application #
7052594
Study Section
Special Emphasis Panel (ZDK1-GRB-6 (M1))
Project Start
2005-07-01
Project End
2010-06-30
Budget Start
2005-07-01
Budget End
2006-07-31
Support Year
1
Fiscal Year
2005
Total Cost
$136,230
Indirect Cost
Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Sun, Dingyuan I; Tasca, Alexia; Haas, Maximilian et al. (2018) Na+/H+ Exchangers Are Required for the Development and Function of Vertebrate Mucociliary Epithelia. Cells Tissues Organs :1-14
Bhakta, Nirav R; Christenson, Stephanie A; Nerella, Srilaxmi et al. (2018) IFN-stimulated Gene Expression, Type 2 Inflammation, and Endoplasmic Reticulum Stress in Asthma. Am J Respir Crit Care Med 197:313-324
Smith, Alex J; Verkman, Alan S (2018) The ""glymphatic"" mechanism for solute clearance in Alzheimer's disease: game changer or unproven speculation? FASEB J 32:543-551
Duan, Tianjiao; Smith, Alex J; Verkman, Alan S (2018) Complement-dependent bystander injury to neurons in AQP4-IgG seropositive neuromyelitis optica. J Neuroinflammation 15:294
Lee, Sujin; Cil, Onur; Diez-Cecilia, Elena et al. (2018) Nanomolar-Potency 1,2,4-Triazoloquinoxaline Inhibitors of the Kidney Urea Transporter UT-A1. J Med Chem 61:3209-3217
Tradtrantip, Lukmanee; Felix, Christian M; Spirig, Rolf et al. (2018) Recombinant IgG1 Fc hexamers block cytotoxicity and pathological changes in experimental in vitro and rat models of neuromyelitis optica. Neuropharmacology 133:345-353
Phuan, Puay-Wah; Veit, Guido; Tan, Joseph-Anthony et al. (2018) ?F508-CFTR Modulator Screen Based on Cell Surface Targeting of a Chimeric Nucleotide Binding Domain 1 Reporter. SLAS Discov 23:823-831
Verkman, Alan S; Yao, Xiaoming; Smith, Alex J (2018) The evolving mystery of why skeletal muscle is spared in seropositive neuromyelitis optica. J Cell Mol Med 22:2039-2040
McGarry, Meghan E; Illek, Beate; Ly, Ngoc P et al. (2017) In vivo and in vitro ivacaftor response in cystic fibrosis patients with residual CFTR function: N-of-1 studies. Pediatr Pulmonol 52:472-479
Thiagarajah, Jay R; Chang, Jeffrey; Goettel, Jeremy A et al. (2017) Aquaporin-3 mediates hydrogen peroxide-dependent responses to environmental stress in colonic epithelia. Proc Natl Acad Sci U S A 114:568-573

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