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High-probability grants
According to our matching algorithm, Wook Joon Chung is the likely recipient of the following grants.
| Years |
Recipients |
Code |
Title / Keywords |
Matching
score |
| 2009 |
Chung, Wook Joon |
R21Activity Code Description:
To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
A Novel Hts Cell-Based Imaging Assay to Identify Chemical Correctors For ??F508-C @ University of Alabama At Birmingham
DESCRIPTION (provided by applicant): Cystic fibrosis (CF) is a lethal genetic disease caused by mutations in the gene that encodes Cystic Fibrosis Transmembrane conductance Regulator (CFTR). The most prevalent mutation is a deletion of phenylalanine at position 508 (?F508-CFTR) that causes defects in folding and trafficking of CFTR and a loss of apical chloride secretion in epithelia. However, once rescued to the cell surface, this ?F508 mutant protein retains functional chloride channel activity and partially restores chloride secretion in the epithelial cells. Attempts at high throughput screens to discover small molecules that correct defects of the ?F508-CFTR mutant have identified compounds with potential therapeutic relevance. Earlier high throughput screens were largely based on functional assays that measure chloride channel activity in live cells. Outcomes of these screens have failed to produce robust and consistent correctors of the ?F508-CFTR misprocessing defect, due to limitations of screening methods. Recent introduction of automated confocal microscopy enables cell based imaging assays and a novel complimentary approach that can be used for high throughput screens of large chemical libraries. The aims of this proposal include 1) establishing a cell based imaging assay for measuring surface density of the ?F508-CFTR using conventional antibodies that recognize epitopes residing in the cystoplasm;2) evaluation of this assay to screen of small molecule libraries for potential drugs that correct folding and trafficking deficiencies of ?F508-CFTR. The successful completion of these experiments will provide an efficient and reliable cell based imaging assay suitable for large scale screens to identify drugs with potential therapeutic relevance to a majority of CF patients. PUBLIC HEALTH RELEVANCE: Cystic fibrosis (CF) is the most prevalent lethal genetic disease among Caucasians. Because most CF patients carry ?F508-CFTR, development of novel high throughput library screens to identify small molecule correctors for ?F508-CFTR defects is crucial to develop potential therapies for the disease. Here, we propose to develop an innovative cell-based imaging assay measuring rescue of ?F508-CFTR on the cell surface for high throughput screening.
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1.009 |