Fluxes through key biochemical pathways such as gluconeogenesis or fatty acid oxidation are thought to be abnormal in transgenic mice and humans with many disorders. Because of the complexity of intermediary metabolism, direct measurements of these fluxes require isotope tracer methods. Earlier studies relied on radioactive tracers, but these methods are limited by radiation exposure and inadequate information yield. Our multidisciplinary lab emphasizes analysis of metabolic networks in vivo by use of 2H or 13C enriched substrates, plus detection of products by advanced NMR or mass spectrometric methods. This combination of safety and high information yield allows investigation of complex metabolic networks in transgenic mice and in humans with metabolic diseases. One current projects is analysis of pyruvate cycling pathways and the impact on gluconeogenesis in mice after liver-specific PEPCK knockout. Other collaborators are examining the contribution of glycerol to gluconeogenesis among patients with HIV and lipoatrophy.
RESEARCH INTERESTS
Cardiovascular radiology; MR methods for the analysis of cardiac metabolism and function, especially intermediary metabolism.