Studying Metabolism for Flux Sake (and to Help People)

Metabolism is central to virtually all cellular functions and contributes to a range of diseases.  A quantitative understanding of how biochemical pathways are dysregulated in the context of diseases such as cancer and metabolic syndrome is necessary to identify new therapeutic targets.  To this end we apply stable isotope tracers, mass spectrometry, and metabolic flux analysis (MFA) to study metabolism in mammalian cells, animal models, and human patients.  Using these approaches we have characterized how proliferating and differentiated cells regulate flux of glucose and amino acids into mitochondria for lipid biosynthesis.  We are particularly interested in the role of branched chain amino acid (BCAA) catabolism in regulating adipose tissue function and lipid diversity. We have also applied MFA to cancer cells with specific oncogenic mutations to identify enzyme targets that selectively inhibit growth, developing new tools to probe compartment-specific metabolic pathways. The application of MFA to disease models greatly improves our ability to characterize intracellular metabolic processes, providing a mechanistic understanding of cellular physiology and metabolic function.