This is a proposal to continue our Cystic Fibrosis (CF) Research and Translational Core Center at the University of California, San Francisco and collaborating institutions. The focus of our Core Center remains the discovery and evaluation of novel small-molecule therapies for CF. The original proposal followed from 5 years of work establishing a unique academic drug discovery program in the laboratories of Dr. Verkman and collaborators to identify and characterize small-molecule modulators of CFTR activity. The proposed Core Center will fund five Cores to support the activities of 2 Pilot Projects and 28 CF-related projects. The Core directors are experienced CF investigators with recognized expertise in their areas of investigation and a history of productive collaboration. The Cores include: High-Throughput Screening (Core A, Alan Verkman, director), Clinical Resources (Core B, Dennis Nielson, director), Cell Models (Core C, Walter Finkbeiner, director), Synthetic Chemistry (Core D, Mark Kurth, director), and Cell &Tissue Bioassays (Core E, Peter Haggie, director). Projects to utilize the cores include the discovery of modulators of epithelial ion transporters (CFTR, CaCCs, ENaC, NKCC, potassium channels), epithelial cell mucin secretion, and Pseudomonas biofilm formation. Other projects to utilize the cores include research on mechanisms of lung disease in CF. The general goal of the research to be enhanced by the Core Center is to develop new small-molecule therapies for CF that can be translated into the clinic.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
2P30DK072517-06
Application #
7991530
Study Section
Special Emphasis Panel (ZDK1-GRB-W (M2))
Program Officer
Mckeon, Catherine T
Project Start
2005-09-15
Project End
2015-05-31
Budget Start
2010-07-14
Budget End
2011-05-31
Support Year
6
Fiscal Year
2010
Total Cost
$1,154,801
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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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
Verkman, Alan S; Tradtrantip, Lukmanee; Smith, Alex J et al. (2017) Aquaporin Water Channels and Hydrocephalus. Pediatr Neurosurg 52:409-416
Cil, Onur; Phuan, Puay-Wah; Gillespie, Anne Marie et al. (2017) Benzopyrimido-pyrrolo-oxazine-dione CFTR inhibitor (R)-BPO-27 for antisecretory therapy of diarrheas caused by bacterial enterotoxins. FASEB J 31:751-760

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