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For the past twenty-five years, my research has centered on the role of free radicals in biological systems. This research has focused on two goals: (a) the development of methods to detect and characterize free radicals generated during cellular activation in vitro and in vivo and (b) the investigation of the biological consequences of these reactive species. Central to the exploration of biologically generated free radicals is the ability to be able to identify and characterize these reactive species at the site of formation. The method of choice is spin trapping/ electron spin resonance (ESR) spectroscopy, which has allowed us to detect free radicals such as hydroxyl radical and nitric oxide in animals in real time. While production of free radicals, including superoxide and hydroxyl radical, has generally been associated with cytotoxicity, the recognition that nitric oxide controls a myriad of important physiologic activities, including host immune response, has ushered in a new era in free radical research. Of particular interest to my laboratory is the role of nitric oxide, generated by the immunological isozyme of nitric oxide synthase, in the control of blood-borne pathogens. Research in the laboratory also focuses on the design and synthesis of dendrimer-linked nitroxides as magnetic resonance imaging (MRI) contrast agents for arthritis. In vivo MR imaging experiments have demonstrated that these compounds are selective contrast agents that specifically bind to joint cartilage. Research is ongoing to determine how early in the development of arthritis can these MRI contrast agents detect changes in cartilage status, becoming valuable diagnostic tools for early detection of arthritis.
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