• Understanding the connection between exercise, exercise capacity, and metabolic health in humans. High exercise capacity (VO2max) is associated with reduced risk of multiple diseases and increased longevity. Likewise, regular physical activity has myriad health benefits. However, the molecular mechanisms underlying the health benefits of exercise and exercise capacity remain incompletely understood. Through my own studies and through participation in the NIH-funded Molecular Transducers of Physical Activity Consortium (MoTrPAC), I am using metabolomics and other tools of systems biology to investigate molecular signals associated with acute exercise and total exercise capacity. A key focus is understanding the set of intrinsic and training-induced molecular adaptations in skeletal muscle and other organs of individuals with high exercise capacity that allow a delayed switchover from fat to carbohydrate oxidation during moderate to high intensity exercise.
• Development of improved analytical methodology for compound identification and quantitation in metabolomics. As a bioanalytical chemist, I am interested in developing improved methodologies to tackle the long-standing challenge of identifying the high proportion of unknown features in untargeted metabolomics data. Moving from unknown features to known compounds mapped to metabolic pathways helps increase the impact of metabolomics data on systems-level understanding of human disease. Additionally, I am working to develop methods which enable higher-sensitivity, reliably quantitative study of a broader range of metabolites in biological samples. To accomplish these goals, I leverage my experience in small and large-molecule mass spectrometry, conventional and nanoscale liquid chromatography, gas chromatography, and multidimensional separations.
• Metabolic studies in an animal model of the metabolic syndrome. Reductions in oxidative capacity have been associated with diseases such as the metabolic syndrome and diabetes. I am studying a strain of rats bred by artificial selection for low and high endurance exercise capacity. Using mass-spectrometry based metabolomics, I aim to detect alterations in metabolism that are associated with reduced oxidative capacity and that may play a role in insulin resistance and obesity. I am also integrating genetic and metabolomic data to differentiate the training-induced and intrinsic contributions to exercise capacity. The research will contribute to understanding of metabolic disease and may offer targets for future treatments
• In vitro and in vivo methods for quantitation of metabolic flux. The study of alterations in cellular metabolism caused by disease requires not only quantification of metabolite concentrations, but also measurement of rates of flux through metabolic pathways. Using stable isotope tracers, I am developing improved methods to quantify metabolic flux and am applying these techniques to studies of cultured cells, isolated tissue, and whole animals, including the low- and high-capacity running rats described above.