"The Rice Research Laboratory, curing cancer one culture dish at a time!"
Research in my laboratory focuses on the mechanism of action of Cloretazine, an anticancer prodrug currently in clinical trials for acute myelogenous leukemia and glioma multiforme. These efforts also include the nitrosoureas, a related class of compounds that are actively used in the clinic. The activity of Cloretazine is a function of two reactive subspecies generated upon base-catalyzed activation in situ: a 2-chloroethylating species and methylisocyanate. The 2-chloroethylating species ultimately forms cytotoxic, interstrand DNA crosslinks, and the carbamoylating activity of methylisocyanate synergizes with the 2-chloroethylating activity, resulting in significant cytotoxicity to neoplastic cells. Projects involve investigations of several enzymes as targets likely to be modified with a carbamoyl group from methylisocyanate in an effort to explain the synergistic cytotoxicity. In addition, the effects of exposure to studied agents on gene expression and signaling pathways in cultured cancer cells is being studied.