Metabolic plasticity enables organisms to respond and adapt to changes in their environment. While the core components of most pathways of intermediary metabolism have long been describe [research4] d – consisting of ~3000 metabolic genes organized in pathways interconnected by 1000s of shared metabolites ­–, it remains poorly understood how the flow of these metabolites is rewired in different metabolic states. This question is particularly relevant in the context of tumors, as cancer cells are frequently starved for nutrients and exposed to toxic waste products due to a combination of increased nutrient consumption and dysfunctional vasculature. Exploring cancer metabolism also provides a tractable system to address a more fundamental question of how metabolic pathways and extracellular cues cooperate to meet the energetic and biosynthetic needs of cells at different metabolic states of metabolic diseases. In the Birsoy lab, we combine a number of cutting-edge techniques – from the development of forward genetics tools (i.e. CRISPR-Cas9 technology) to metabolomics – to elucidate how cellular metabolism contributes to human disorders such as cancer and inborn errors of metabolism.

Our long term research goal is to understand how metabolic pathways in mammalian cells are rewired by their nutrient environment and, further, to determine whether these pathways present metabolic liabilities that could be exploited for disease therapy.