My laboratory carries out basic and translational research relevant to human diseases, with a major focus on mechanisms of the inflammatory response and oxidative stress, as well as the cell biology and biochemistry of human phagocytic cells. We have contributed to fundamental understanding of the generation of reactive oxygen species (ROS) by the phagocyte NADPH oxidase system, the biological roles of these products, and the genetics and biochemistry of NADPH oxidase deficiency. In recent years we have turned our attention to the structure, function, and physiologic roles of several novel non-myeloid members of the NADPH oxidase (NOX) gene family, focusing particularly on the involvement of these oxidases in disease pathogenesis and the transcriptional regulation of genes that are relevant to the biology of aging. My recent studies include mechanistic work on neurodegenerative disorders, especially Parkinson’s disease.
El Jamali A, Valente AJ, Clark RA. Regulation of phagocyte NADPH oxidase by hydrogen peroxide through a Ca(2+)/c-Abl signaling pathway. Free Radic Biol Med. 2010 Mar 15;48(6):798-810.
Biju K, Zhou Q, Li G, Imam SZ, Roberts JL, Morgan WW, Clark RA, Li S. Macrophage-mediated GDNF delivery protects against dopaminergic neurodegeneration: a therapeutic strategy for Parkinson's disease. Mol Ther. 2010 Aug;18(8):1536-44.
Imam SZ, Zhou Q, Yamamoto A, Valente AJ, Ali SF, Bains M, Roberts JL, Kahle PJ, Clark RA, Li S. Novel regulation of parkin function through c-Abl-mediated tyrosine phosphorylation: implications for Parkinson's disease. J Neurosci. 2011 Jan 5;31(1):157-63.
Musset B, Clark RA, DeCoursey TE, Petheo GL, Geiszt M, Chen Y, Cornell JE, Eddy CA, Brzyski RG, El Jamali A. NOX5 in human spermatozoa: expression, function, and regulation. J Biol Chem. 2012 Mar 16;287(12):9376-88.
Valente AJ, Clark RA, Siddesha JM, Siebenlist U, Chandrasekar B. CIKS (Act1 or TRAF3IP2) mediates Angiotensin-II-induced Interleukin-18 expression, and Nox2-dependent cardiomyocyte hypertrophy. J Mol Cell Cardiol. 2012 Jul;53(1):113-24.