The CF Cell & Tissue Bioassays Core (Core D) is an important component of the UCSF CF Research and Translation Core Center. The major objective of the Core is to test the efficacy of CF-targeted small molecules discovered by high-throughput screening (HTS; performed by Core A) in physiologically relevant pre-clinical assays. This objective is accomplished by performing electrophysiological and optical assays that probe ion channel and epithelial cell function in CF-relevant cell and tissue models. Assays use immortalized cell culture models, primary cell cultures derived from human sources, three-dimensional models including organoids, and tissue samples such as airway fragments from non-CF and CF subjects (provided by Core B, Cell & Tissue Models). The most heavily used resource in the Core are Ussing chambers for analysis of short-circuit current which is performed to validate hits identified by HTS, determine hit efficacy, provide structure-activity relationship data during hit-to-lead optimization, and assess lead efficacy in human airway tissue samples from CF and non-CF subjects. Other major Core D resources include optical assays of CF-relevant airway properties, including measurement of airway surface liquid and submucosal gland secretions in human cell cultures and airway tissues from CF and non-CF subjects. Many of the optical assays provided by Core D were developed to investigate CF lung disease mechanisms and are uniquely available at UCSF. Core D also carries out electrophysiological and optical assays to support basic and translational research on CF pathophysiology and assay development for screening. Of the 25 projects in the research base, 20 will use Core D resources.
A critical step in preclinical development of CF-targeted drugs is assessment of compound efficacy in validated cell and tissue based assays. The major objective of Core D (CF Cell & Tissue Bioassays) of the UCSF CF Research and Translation Core Center is to test efficacy of compounds discovered by our Center in appropriate assays. A secondary goal of the Core is to develop novel assays that will facilitate or improve compound testing.
|Piechowicz, Katarzyna A; Truong, Eric C; Javed, Kashif M et al. (2016) Synthesis and evaluation of 5,6-disubstituted thiopyrimidine aryl aminothiazoles as inhibitors of the calcium-activated chloride channel TMEM16A/Ano1. J Enzyme Inhib Med Chem 31:1362-8|
|Bonser, Luke R; Zlock, Lorna; Finkbeiner, Walter et al. (2016) Epithelial tethering of MUC5AC-rich mucus impairs mucociliary transport in asthma. J Clin Invest 126:2367-71|
|Haggie, Peter M; Phuan, Puay-Wah; Tan, Joseph-Anthony et al. (2016) Inhibitors of pendrin anion exchange identified in a small molecule screen increase airway surface liquid volume in cystic fibrosis. FASEB J 30:2187-97|
|Suzuki, Shingo; Sargent, R Geoffrey; Illek, Beate et al. (2016) TALENs Facilitate Single-step Seamless SDF Correction of F508del CFTR in Airway Epithelial Submucosal Gland Cell-derived CF-iPSCs. Mol Ther Nucleic Acids 5:e273|
|Flores, Alyssa M; Casey, Scott D; Felix, Christian M et al. (2016) Small-molecule CFTR activators increase tear secretion and prevent experimental dry eye disease. FASEB J 30:1789-97|
|Cil, Onur; Haggie, Peter M; Phuan, Puay-Wah et al. (2016) Small-Molecule Inhibitors of Pendrin Potentiate the Diuretic Action of Furosemide. J Am Soc Nephrol 27:3706-3714|
|Jin, Byung-Ju; Smith, Alex J; Verkman, Alan S (2016) Spatial model of convective solute transport in brain extracellular space does not support a "glymphatic" mechanism. J Gen Physiol 148:489-501|
|Cil, Onur; Phuan, Puay-Wah; Lee, Sujin et al. (2016) CFTR activator increases intestinal fluid secretion and normalizes stool output in a mouse model of constipation. Cell Mol Gastroenterol Hepatol 2:317-327|
|Esteva-Font, Cristina; Jin, Byung-Ju; Lee, Sujin et al. (2016) Experimental Evaluation of Proposed Small-Molecule Inhibitors of Water Channel Aquaporin-1. Mol Pharmacol 89:686-93|
|Walentek, Peter; Quigley, Ian K; Sun, Dingyuan I et al. (2016) Ciliary transcription factors and miRNAs precisely regulate Cp110 levels required for ciliary adhesions and ciliogenesis. Elife 5:|
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