Dr. Cifuentes-Pagano’s research interests focus on the understanding of the molecular mechanisms of action of novel NADPH oxidase isoforms and their regulation in the vasculature. The phagocyte NADPH oxidase (or respiratory burst oxidase) is a well-characterized reactive oxygen species (ROS)-generating system that catalyzes the one-electron reduction of oxygen to O2-, the precursor to a variety of other reactive oxygen species. The NADPH oxidase paradigm is a multi-subunit enzyme complex that includes two membrane-spanning subunits, p22-phox and nox2 , and three cytoplasmic subunits, p40-phox, p47-phox and p67-phox. Our laboratory was the first to discover a nox2-based oxidase in the vasculature and to develop specific inhibitors targeting this robust source of ROS. Since that initial discovery, various isoforms of NADPH oxidase have been described which differ from the nox2 system in unique modifications of their nox-subunit amino acid sequence as well as the cytoplasmic components that they require. Besides their structural differences, the various isoforms present differential tissue and cellular distribution. The multi-level complexity of this family of proteins provides an opportunity to develop new tools to dissect the role of each of the isoforms in vascular function and pathology.
http://paganolab.pitt.edu/