Multiple Myeloma is a malignant plasma cell proliferative disorder. Plasma cells are white blood cells that produce large volume of antibodies and they are originating in the lymphatic tissue. Multiple myeloma is incurable with existing therapies. Chemotherapeutic drugs and radiation therapy provide some benefit but all patients relapse with fatal outcome. It is therefore very important to understand how best to eliminate the tumor cells in their normal microenvironment. Malignant cells, in general, are under oxidative stress due to their aberrant metabolic regulations. Superoxides and hydrogen peroxides, which are the key regulator molecules for cellular redox balance, are frequently being observed to be produced in excess in several form of malignancy. Our objective in this research is the use of chemotherapeutic drugs in our case dexamethasone in combination with radiation to selectively induce metabolic oxidative stress to myeloma cells that may be more prone to undergo cell death compared to non-transformed cells. Other objective in this research is obtaining a mechanism of acquired resistance in myeloma cells by modulating the redox parameters with antioxidant enzymes such as superoxide dismutases and catalase. In our laboratory we use myeloma and bone marrow stromal cell lines of murine and human origin. For knockdown studies we are utilizing short hairpin RNA (shRNA) sets that are obtained from the RNAi consortium (TRC) (Open Biosystems). As a part of my project I performed DNA mini-preparation of shRNA sets for SOD1, SOD2 and catalase. I saw the process of generation of recombinant lentiviruses where transient transfections were performed in a packaging cell line. These recombinant lentiviruses were harvested and used for knockdown studies in murine and human cell lines. I performed western blots where cell lysates were run on SDS-PAGE and probed for SOD1, SOD2 and catalase antibodies to detect these immunoreactive proteins. Then I perform enzyme activity assays for these enzymes. I have also done a SOD2 over expression study where we used human cell lines. I expect to determine if over expression of SODs and/or catalase may render the myeloma cells resistant to chemotherapeutic drugs and/or radiation.