Te-Chang Lee

The long-term goals of my laboratory are: (1) to understand the mechanisms underlying which sustained arsenic stress reprograms the gene expression via epigenetic alterations; (2) to explore the therapeutic application of inorganic arsenic; and (3) to investigate and develop novel anticancer drugs. Chronic exposure to inorganic arsenic (iAs) continues to be a severe toxicological and pathological problem in humans. During the past decade, we focused on the gene reprogram in cells under sustained genotoxic stress by iAs and several novel genes were shown to have oncogenic potential. Our recent studies have shown that long-term exposure of cells to iAs induces changes of DNA methylation and chromatin structure, hence results in gene expression profile change and malignant transformation. Arsenic trioxide (ATO) has been approved as effective drug against refractory acute promyelocytic leukemia. Since ATO also inhibits DNA repair, we are further investigated its application strategy for treatment of other solid tumors. Via collaboration with Dr. T. L. Su, a medicinal chemist in IBMS, we have demonstrated that several newly synthesized bifunctional alkylating agents are potent anticancer agents. Some of them were even able to overcome the MDR cancer cells.