Michael James Lukey

Proliferative signals in mammalian cells drive biosynthetic programs that support cell growth and replication. In healthy cells this process is tightly regulated by growth factors, but in cancer cells oncogenic lesions can result in continuous signaling to the metabolic machinery. Oncogene-driven metabolic reprogramming supports tumorigenesis but renders cells sensitive to specific metabolic stresses, a phenomenon that is exploited for cancer therapy. Because the distribution of nutrients varies markedly between organs, cancer cells growing at different sites in the body – and in different regions of the tumor microenvironment—must employ a range of metabolic strategies to fuel their growth. We aim first to understand the nature and regulation of metabolic adaptations in the different stages of cancer, and then to develop therapeutic strategies that target resulting vulnerabilities. We are especially interested in the biochemical processes underlying nutrient sensing and metabolic/redox homeostasis, including regulation of the protein post-translational modification landscape by reactive metabolites. We are also exploring the reciprocal connections between tumor metabolism and host physiology, recognizing that metabolic therapies must be designed to synergize with, and not to antagonize, the anti-tumor immune response.