Dr. Letai studies the apoptotic pathway in cancer cells, and how it may be selectively targeted to induce cancer death. All cancer cells need to block apoptosis to progress as a tumor. The exact mechanisms selected to avoid apoptosis have important implications in determining subsequent response to targeted and conventional chemotherapeutic agents. Dr. Letai’s laboratory has developed a strategy called BH3 profiling that can classify the type of block in apoptosis used by a particular cancer cell. This knowledge can then be used to predict sensitivity to agents that target the intrinsic apoptotic pathway. For instance, BH3 profiling can predict cellular response to the BCL-2 antagonist, ABT-737. Dr. Letai assisted in preclinical studies on ABT-737, especially studying its effects on CLL, ALL, AML, and breast cancer. Since many chemotherapeutic agents use the intrinsic apoptotic pathway to kill cells, it has emerged that BH3 profiling can predict response to conventional agents by cancer cell lines as well. Dr. Letai’s laboratory is currently testing the ability of BH3 profiling to predict drug response. In addition, apoptosis plays an important role in many non-malignant settings. The Letai laboratory is exploring how BH3 profiling can be used to understand the apoptotic response in lymphocytes and other non-malignant tissues following a wide variety of stimuli.