The High-Throughput Screening (HTS) Core carries out target- and phenotype-based screens of small- molecule libraries. The HTS core will support the activities of twelve CF-related screening projects, including correctors and potentiators of ?F508-CFTR, and various CF-relevant ion transport and inflammation targets. The instrumentation available for screening includes a fully automated screening platform with liquid handling and two plate readers, and two separate plate readers with stackers. Plate-readers provide fluorescence, polarization, absorbance, and luminescence readout. Functions of the Core include compound storage and handling, assay design and validation, assay execution, and data analysis. Core resources also include HPLC, LC/MS, and NMR instrumentation for compound quality control. The Core also carries out optimization of validated initial `hits' (active compounds) by screening commercially available analogs. Further `hit-to-lead' development is done on individual projects in consultation with the Synthesis Core (Core C). Having operated the HTS Core for the past 9 years, the Core established practical procedures for efficient and cost-effective compound screening, quality control, and hit-to-lead optimization.

Public Health Relevance

The High-Throughput Screening Core carries out target- and phenotype-based screens of small-molecule libraries in order to identify new drug candidates for cystic fibrosis therapy. The functions of the Core include compound storage and handling, assay design and validation, assay execution and data analysis.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Center Core Grants (P30)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Francisco
San Francisco
United States
Zip Code
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

Showing the most recent 10 out of 276 publications