The basic and clinical research activities of the Freeman Laboratory focus on the eukaryotic cell production, reactions and signal transduction properties of oxidizing and free radical inflammatory mediators (e.g., superoxide, hydrogen peroxide, nitric oxide (NO), peroxynitrite, nitrogen dioxide, oxidized/nitrated lipids). In particular, we are interested in the action of these species as both redox signaling mediators under basal conditions and as pathogenic agents in inflammatory diseases. Our observations regarding O2 and NO-derived reactive species have lent new insight into redox-dependent cell signaling and have revealed new therapeutic strategies for treating acute inflammation, metabolic syndrome, respiratory disorders and cardiovascular diseases.
In the late 1980s, his group studied the cellular and subcellular organelle production of superoxide and hydrogen peroxide. Following the landmark description of endothelial-derived relaxing factor (EDRF) as the free radical NO, the Freeman laboratory pioneered the concept that the inflammatory and signal transduction mediator NO displays unique redox signaling actions following reaction with superoxide, oxidizing fatty acids and heme peroxidases. The “oxidative inactivation” of NO is a kinetically fast reaction, yielding “reactive nitrogen species” as products. This array of reactions of O2-derived species with NO can serve to both impair and transduce NO signaling via non-cGMP dependent mechanisms.