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Office: N-606 Research Interests: Mechanisms of reactive oxygen species production from mammalian mitochondrial respiratory chain enzymes and its relation to toxicological insult, neurodegenerative diseases, and aging; and developmental and long-term effects of prenatal lead exposure on neural retinal development in mice. Mechanism of Mitochondrial NADH–ubiquinone oxidoreductase (Complex I) in health and disease: NADH–ubiquinone oxidoreductase (Complex I) is the first site for energy conservation in the mitochondrial respiratory chain, and is the least understood component of the oxidative phosphorylation system. Biochemical investigation of complex I is limited and difficult due to its large size, lipid-dependence, sensitivity to classic isolation procedures, and general lack of structural and mechanistic information. For his doctoral dissertation, Dr. Johnson isolated Complex I from bovine heart muscle in a reproducible and active form and characterized the enzyme for: reactive oxygen species production, kinetic interactions with various ubiquinone substrates and inhibitors, thermodynamic and kinetic properties of ubiquinone reduction and superoxide anion production, interactions with mitochondrial ubiquinol–cytochrome c oxidoreductase (complex III), and stable ubisemiquinone free radical formation. Of clinical importance, the high rates of superoxide anion production characterized in isolated complex I may represent activities of the enzyme present in many disease states such as Parkinson’s disease, Alzheimer’s disease, and other neurodegenerative states. Further reconstitution, kinetic, and thermodynamic characterization of complex I activity will enhance our knowledge of the mechanism of ubiquinone reduction, proton pumping, and interaction with the other components of the mitochondrial respiratory chain in the absence of a crystal structure. Currently, Dr. Johnson seeks to continue his doctoral research and characterize reactive oxygen species production from bovine heart mitochondria and isolated respiratory chain components induced by the chemotherapeutic agent doxorubicin/adriamycin. The obtained results will provide clinicians with insight into the specific site and mechanism of doxorubicin-induced ROS production in the treatment of cancer. Ultimately, such knowledge may lead to improved treatment strategies of cancer using doxorubicin with minimal toxic side effects.
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