Manipulating Cell Death Pathways for Improved Cancer Therapy
Our research is focused on manipulating cell death pathways in order to successfully eradicate cancer cells. Toward this goal we study three cancer-relevant proteins: the p53 and p14ARF tumor suppressor proteins, and the cancer-critical survival protein HSP70. Our work on the p53 tumor suppressor protein focuses on the fact that there are three genetic variants of the p53 gene in human populations that affect the ability of this protein to suppress tumor development. Two of these genetic variants, or polymorphisms, are significantly more common in African and Hispanic Americans, and may explain existent disparities in risk for cancer and other diseases, such as diabetes, in these populations. Our work directly addresses this hypothesis.
Our work on the p14ARF tumor suppressor protein and the HSP70 molecular chaperone, focuses on the involvement of these proteins in a cell survival process called autophagy. Autophagy is the process whereby cells under nutritional or other stress ingest bits and pieces of their own cellular material in order to generate nutrients and energy for continued survival. The emerging paradigm in cancer research is that tumors need autophagy in order to survive. Our research indicates that p14ARF and HSP70 play key roles in autophagy and survival, especially in tumor cells. Notably, we have recently identified a small molecule inhibitor of HSP70 that is an effective and potent anti-cancer agent for several tumor types, including Burkitts lymphoma, acute myeloid leukemia and melanoma. We are pursuing studies of this compound, as well as modified derivatives, as a novel means for anticancer therapy.