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Assem G. Ziady, Ph.D.
Assistant Professor
agz2@case.edu
BRB Room 824
(216) 368 4628 Phone
(216) 368 4223 Fax
Biography
Dr. Ziady received his undergrad degree in Biochemistry at Boston College, where he was presented Scholar of the college in 1993. In 1998 he received his Ph.D. in Cell Physiology from the Department of Biophysics at Case Western Reserve. As a Post-doctoral fellow Dr. Ziady studied gene delivery and lung gene therapy until 2003. While working he was presented the American Society of Gene Therapy, Excellence In Research award and the Research Merit award. During his fellowship Assem was awarded the Cystic Fibrosis Foundation fellowship grant in 1999. He has also worked on protein mass spectrometry as a visiting fellow at the Cleveland Clinic Foundation. Dr. Ziady joined the Department of Pediatrics in December 2003.
Research Interests
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 such as cytokines, transcription factors, kinases, and phosphatases implicated in their exaggerated response to inflammatory stimulus. Anti-inflammatory therapy with agents such as ibuprofen has been shown to be beneficial,slowing lung deterioration in patients. However, the origin of drug mechanisms involved in limiting this inflammatory response as well as the interplay between defects in cystic fibrosis transmembrane regulator (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. 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. These studies have the prospect of elucidating cell-wide mechanisms involved in the CF inflammatory response on the protein level, and identifying specific therapeutic targets that play central roles in evoking these responses.
These studies have led to the discovery of a paradoxical down regulation of the antioxidant response element (ARE) in CF epithelia. The transcription factor central to ARE, Nrf2, exhibits diminished expression and activity in CF cells leading to the reduced expression of a number of peroxidase enzymes that regulate steady state hydrogen peroxide. A concurrent decrease in catalase expression and increase in SOD2 expression results in the accumulation of interacellular hydrogen peroxide, which is a potent stimulator of NF-kB, Sp1, and AP-1 mediated inflammatory responses. Therefore our discovery is very relevant to CF and our studies have shown that treatment with antioxidants can ameliorate exaggerated cytokine production without affecting normal responses, which is a very desirable outcome in CF therapy.
Publications
Ko IK, Ziady AG, Lu S, Kwon YJ.
"Enhanced gene delivery by degradable and easily tunable non-viral carriers"
Biomaterials. 29(28):3872-81, 2008.
Ziady AG, Kinter M.
"Protein sequencing with tandem mass spectrometry"
Methods in Molecular Biology. 2008, In press.
Sun W, Ziady AG.
"Real-Time Imaging of Gene Delivery and Expression with DNA Nanoparticle Technologies"
Methods in Molecular Biology. 2008, In press.
Ziady AG, Davis PB.
"Infection versus Inflammation" in Bush, A., Alton, E., Davies, J., Griesenbach, U., Jaffe, A. (eds) Cystic Fibrosis in the 21st Century
Prog in Resp Res Basel, Karger 2006 vol 34 pp. 122-130.
Ziady AG, Davis PB
"Current prospects for gene therapy of cystic fibrosis"
Curr Opin Pharmacol. 6(5):515-521, 2006.
Yike I, Distler AM, Ziady AG, Dearborn DG
"Mycotoxin adducts on human serum albumin: biomarkers of exposure to Stachybotrys chartarum"
Environ Health Perspect. 2006 Aug;114(8):1221-6.
Konstan MW, Davis PB, Wagener JS, Hilliard KA, Stern RC, Milgram LJ, Kowalczyk TH, Hyatt SL, Fink TL, Gedeon CR, Oette SM, Payne JM, Muhammad O, Ziady AG, Moen RC, Cooper MJ
"Compacted DNA nanoparticles administered to the nasal mucosa of cystic fibrosis subjects are safe and demonstrate partial to complete cystic fibrosis transmembrane regulator reconstitution"
Hum Gene Ther. 15(12):1255-69, 2004
A.G. Ziady, J. Kim, J. Colla, and P.B. Davis
"Defining strategies to extend duration of gene expression from targeted compacted DNA vectors"
Gene Therapy.11(18):1378-1390, 2004
A.G. Ziady, C.R. Gedeon, O. Muhammad, V. Stillwell, S. Oette, T. Fink, W. Quan, T. Kowalczyk, S.L. Hyatt, A. Peischl, J.E. Seng, R. Moen, M.J. Cooper, P.B. Davis
"Minimal toxicity of stabilized compacted DNA in the murine lung"
Molecular Therapy. 8(6): 948-956, 2003
A.G. Ziady, C.R. Gedeon, T. Miller, W. Quan, J.M. Payne, S.L. Hyatt, T. Fink, O. Muhammad, S. Oette, T. Kowalczyk, M.K. Pasumarthy, R. Moen, M.J. Cooper, P.B. Davis
"Transfection of Airway Epithelium by Stable PEGylated Poly-L-lysine DNA Nanoparticles In Vivo"
Molecular Therapy. 8(6): 936-947, 2003
A.G. Ziady, P.B. Davis, and M.W. Konstan
"Novel non-viral gene transfer therapy for cystic fibrosis"
Expert Opinion on Biological Therapy. 3:449-458, 2003
Ziady AG, Davis PB
"Receptor-directed molecular conjugates for gene transfer"
Methods Molecular Medicine 69:25-48, 2002
Ziady AG, Kelley TJ, Milliken E, Ferkol T, Davis PB
"Functional evidence of CFTR gene transfer in nasal epithelium of cystic fibrosis mice in vivo following luminal application of DNA complexes targeted to the serpin-enzyme complex receptor"
Molecular Therapy 5(4):413-9, 2002
Ziady AG, Ferkol T, Dawson DV, Perlmutter DH, Davis PB
"Chain length of the polylysine in receptor-targeted gene transfer complexes affects duration of reporter gene expression both in vitro and in vivo"
Journal of Biological Chemistry 274(8):4908-16, 1999
Ziady AG, Ferkol T, Gerken T, Dawson DV, Perlmutter DH, Davis PB
"Ligand substitution of receptor targeted DNA complexes affects gene transfer into hepatoma cells"
Gene Therapy 5(12):1685-97, 1998
Ziady AG, Perales JC, Ferkol T, Gerken T, Beegen H, Perlmutter DH, Davis PB
"Gene transfer into hepatoma cell lines via the serpin enzyme complex receptor"
Am J Physiol. 273(2 Pt 1):G545-52, 1998 |
