Signal Transduction and Cancer Metabolism
Tumor cells display fundamental changes in metabolism driven by oncogenic signaling, and enhance nutrient uptake to meet increased bioenergetic demands of proliferation. However, as tumors grow, increased metabolite uptake can outstrip the supply of nutrients. How tumor cells survive these temporary periods of nutrient deprivation is unclear, but such survival is necessary for tumorigenesis to persist. The major goal of our laboratory is to delineate the strategies used by tumor cells to survive periods of nutrient deprivation and then to develop novel therapies targeting nutrient-sensing pathways of neoplastic cells.  We recently discovered that protein phosphatase 2A (PP2A) plays a critical role in the regulation of cell survival under stress conditions. However, it has been difficult to pin down the role of PP2A in cell survival because it regulates a myriad of signaling pathways by assembly of different complexes. Thus, our studies focus on: 1) identifying the specific PP2A binding proteins/regulatory subunits and their substrates that regulate cell survival under conditions of nutrient limitation; 2) determining the role of PP2A binding proteins/regulatory subunits in tumor development. In our laboratory, we employ a variety of tools including biochemistry, metabolic analysis, cell biology, bioinformatics, and mouse models to address our biological questions. Our long-term goal is to identify the signals that allow communication between oncogenic pathways and tumor cell metabolism and to develop novel therapeutics targeting metabolic differences between rapidly-proliferating cancer cells and normal cells.