Vontz Center for Molecular Studies
University of Cincinnati Medical Center
3125 Eden Avenue
Cincinnati, OH 45267-0521
david [dot] plas [at] uc [dot] edu
The Plas lab studies signal transduction control of cancer cell metabolism. Dramatic alterations in cellular metabolism are frequently associated with oncogenic transformation, but cancer-driving mutations only rarely affect metabolic enzymes themselves. More commonly, oncogenic mutations hijack cellular metabolism by altering key signaling pathways, through kinases such as S6K1. We are testing targeted therapeutics, including kinase inhibitors, that interrupt oncogenic signal transduction to counteract cancer cell metabolism and sensitize cancer cells to undergo programmed cell death.
Our lab works in 3 major areas, all facets of an overall cancer research program that targets metabolism by inhibiting mTORC1-S6K1 metabolic control signals. 1) We are identifying cancers with increased glycolysis resulting from FOXO inactivation, and testing the efficacy of interrupting mTORC1-S6K1 to compensate for loss of FOXOs. 2) We are developing novel approaches for targeting S6K1 to reduce oncogenic glycolysis and apoptosis resistance in PTEN-deficient cancers. 3) We are identifying and targeting a recently discovered mechanism that permits cancer cells to switch from glycolytic metabolism to an oxidative program, allowing cancer cells to survive during treatment with targeted therapeutics.
By targeting metabolic control signals, the overall research program aims to produce novel therapeutic strategies for leukemia, solid tissue tumors, and CNS tumors.