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Assem G. Ziady
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Assistant Professor |
Inflammation in cystic fibrosis is excessive, and typically leads to lung damage and eventual lung failure. A number of studies have found that CF cells, especially airway epithelia produce elevated levels of proteins implicated in their exaggerated response to inflammatory stimulus. The origin of drug mechanisms involved in limiting this inflammatory response as well as the interplay between defects in CFTR and the inflammatory cascades are not well understood. Our studies make use of mass spectrometry to analyze changes in protein expression levels and post-translational modifications in CF cells in response to inflammatory stimulus with particular attention paid to redox proteins. We examine these changes in cultured cells designed to exhibit the CF phenotype that are well matched to non CF controls of identical cell-lineage origin. Our aim is to identify proteins that become altered in the CF state and examine whether these play a role in inflammatory response mechanisms. Furthermore, we test whether post-translational modifications that alter protein function, such as oxidation, occur differently in CF than non-CF cells in response to inflammation, and identify them.
Another focus in the lab revolves around the use of molecular conjugates to compact and deliver DNA nanoparticles to target cell types in the lung. These studies have yielded data contributing to 2 patents, numbers 5,972,901 and 6,200,801 issued in 1999 and 2000, respectively. Targeting DNA nanoparticles to specific cells is advantageous as it amplifies treatment effect and limit undesirable side effects due to expression in non essential cells.