I have been involved in analytical biochemistry for over forty years and have experience in magnetic resonance, gas and liquid chromatography and mass spectrometry. For the past twenty years I have focused more on mass spectrometry. I joined the mass spectrometry laboratory of the Division of Medical Genetics in the Department of Pediatrics at Duke. This laboratory, under the direction of David Millington, is internationally recognized as pioneering the use of mass spectrometry for diagnosing inborn errors of metabolism. My initial role in this laboratory was to establish a shared resource to provide electrospray ionization mass spectrometry support for the various research groups within Duke Medical Center. Later, I became more involved with the diagnostic effort of the laboratory, expanding the mass spectrometry repertoire and providing technical oversight of the laboratory. Collaborative ties were established with Chris Newgard, James Bain and Olga Ilkayeva in 2003 and the metabolomics core within the Sarah W. Stedman Nutrition and Metabolism Center was born. I joined the metabolomics laboratory within the Stedman Center as its technical director in 2005.
The major focus of my research at the Stedman Center has been devoted to developing methods for quantitative metabolic profiling. High throughput methods have been developed for profiling amino acids, acylcarnitines, acyl CoAs, ceramides, sphingomyelins and common phospholipids using flow injection tandem mass spectrometry. Metabolites are quantified by isotope dilution techniques using stable heavy isotope labeled standards or non-physiologic analogues. These methods have been adapted to many different tissue types from cells to whole animals. This toolbox has been used extensively by colleagues within the DMPI as well as by extramural collaborators of the Newgard and Muoio groups. Metabolic profiling has been used by our group to uncover metabolite signatures, in humans, associated with obesity, diabetes, and cardiovascular disease. (1,3,4,5) The origins and potential consequences of these signatures have been further investigated in animal models (2,3) . I have a particular interest in mitochondrial fatty acid oxidation and understanding how different fatty acids are metabolized. Acylcarnitines are very informative in this regard but flow injection techniques suffer from the inability to distinguish among the numerous isomeric and isobaric species. A new LCMS has been developed which has revealed that the spectrum of acylcarnitine species in different tissue types is far more complex than previously thought. Efforts to resolve their identities are underway.