Research Goals of Dr. Oberley
Research in my laboratory centers on understanding the role of reactive oxygen species in neoplasia. Because reactive oxygen species are substrates for antioxidant enzymes, I am also studying the role of antioxidant enzymes in cancer. It has been suggested in many experimental tumor models that a prooxidant state may be involved in carcinogenesis. It has also been established that lowered antioxidant enzymes are a general property of neoplastic cells. My laboratory is currently studying the effect of transfection of cDNAs for antioxidant enzymes into tumor cells. Studies in malignant melanoma, fibrosarcoma, and breast cancer have all demonstrated that transfection completely inhibits the malignant phenotype as shown in nude mice cell transplantation assays. The mechanism of inhibition of tumor formation remains unknown. Since it is now well established that cellular reduction-oxidation (redox) state affects signal transduction pathways which regulate cell division, I am currently measuring redox in cells transfected with antioxidant enzymes to see if there is direct correlation with inhibition of the malignant phenotype. If a direct correlation between redox and inhibition of malignancy can be demonstrated, new cancer treatment therapies can rapidly be proposed and tested.
Antioxidant defense - enzymes. Three important intracellular enzymes constitute antioxidant defense; superoxide dismutase (SOD), catalase, and the GSH peroxidase/GSSG reductase system. SOD catalyzes the dismutation of superoxide, catalase the conversion of hydrogen peroxide to H2O and O2, while GSH peroxidase transfers electrons from GSH to reduce peroxides to water. The oxidized glutathione produced (GSSG) is re-reduced back to GSH by glutathione reductase utilizing NADPH produced by the HMP shunt.acting as an enzyme cofactor