Cellular energy metabolism is connected to all major growth factor signaling networks and influences cell behaviors like proliferation and differentiation. Metabolic rewiring is a hallmark of aberrant growth in cancers, and directs developmental signals.

Using multi-photon imaging of natural redox ratios (indicators of metabolic activity) in live mouse skin, we previously found that metabolic changes are among the first observable responses to oncogenic mutations in skin stem cells. Tracking these cells over time in the live animal revealed dynamic modulation of redox states between wild-type and mutant cells that determine their phenotypic outcome in the skin. Interestingly, similar redox changes occur during normal development when signaling pathways are activated.

Our lab aims to study how changes in metabolism connect with and dictate dynamic changes in cell state in response to growth cues. By imaging of cell states and cell fates in parallel with their metabolic states in the live animal, we map out nodes of growth factor signaling sensitive to metabolic states in cancer and normal development.

We use complementary stable isotope tracer methods and metabolomics to dissect mechanistically the reasons underlying changes in redox states. With this comprehensive approach, combining high-resolution imaging over time with biochemical dissection of metabolic pathways, we aim to explore how cellular metabolic networks dictate dynamic cell behavior and fates in both healthy and diseased states.

Contact
Anupama Hemalatha