The Metabolomics Core at the University of Utah was initiated in 2006 with funding from NIH/NIDDK in the form of a Centers of Excellence in Molecular Hematology. From its inception the Core has performed non-targeted analysis of the metabolome using gas-chromatography based mass spectrometry (GC-MS). The Core initially focused on the relationship of metals in metabolism, searching for the underlying causes of disease states when key metal metabolites were either in excess or limiting. It has broadened its focus to other disease, especially those caused by mutations in mitochondrial proteins. The Core has been highly successful in this endeavor with resulting data has been included in a number of publications. Not all metabolites are detected using this GC-MS based approach. The Core over the past year has used an older PE SCIEX API 365 triple quadrupole LC-MS/MS to perform targeted metabolomics with success. Unfortunately this instrument suffers from major limitations;it is older, unreliable and does not perform non-targeted analysis. This instrument needs to be replaced with a modern, high-end instrument which has increased sensitivity, greater dynamic range and importantly improved reliability. We propose the purchase of an Agilent 6550 Quadrupole-Time-Of-Flight (QTOF) mass spectrometer with an Agilent 1290 Infinity ultrapressure liquid chromatography system. This system will complement our current Waters GCT-Premier GC-MS and will be used immediately at full capacity. We are pursuing a number of medically related metabolomics projects currently, from basic research in understanding the causes of disease to actual patient studies.
The addition of the Agilent 6550 QTOF system will allow for the non-targeted analysis of the metabolome not detected by GC-MS. This will allow for the detection of many medically important metabolites not currently detected including acyl-carnitines, porphyrins, and lipids.
|Burch, Joseph S; Marcero, Jason R; Maschek, John Alan et al. (2018) Glutamine via ?-ketoglutarate dehydrogenase provides succinyl-CoA for heme synthesis during erythropoiesis. Blood 132:987-998|
|Szaniawski, Matthew A; Spivak, Adam M; Cox, James E et al. (2018) SAMHD1 Phosphorylation Coordinates the Anti-HIV-1 Response by Diverse Interferons and Tyrosine Kinase Inhibition. MBio 9:|
|Cracan, Valentin; Titov, Denis V; Shen, Hongying et al. (2017) A genetically encoded tool for manipulation of NADP+/NADPH in living cells. Nat Chem Biol 13:1088-1095|
|Simcox, Judith; Geoghegan, Gisela; Maschek, John Alan et al. (2017) Global Analysis of Plasma Lipids Identifies Liver-Derived Acylcarnitines as a Fuel Source for Brown Fat Thermogenesis. Cell Metab 26:509-522.e6|
|Tanner, Jason M; Bensard, Claire; Wei, Peng et al. (2017) EWS/FLI is a Master Regulator of Metabolic Reprogramming in Ewing Sarcoma. Mol Cancer Res 15:1517-1530|
|Cox, James E; Thummel, Carl S; Tennessen, Jason M (2017) Metabolomic Studies in Drosophila. Genetics 206:1169-1185|
|Strachan, Lauren R; Stevenson, Tamara J; Freshner, Briana et al. (2017) A zebrafish model of X-linked adrenoleukodystrophy recapitulates key disease features and demonstrates a developmental requirement for abcd1 in oligodendrocyte patterning and myelination. Hum Mol Genet 26:3600-3614|
|St Clair, Samantha L; Li, Hongde; Ashraf, Usman et al. (2017) Metabolomic Analysis Reveals That the Drosophila melanogaster Gene lysine Influences Diverse Aspects of Metabolism. Genetics 207:1255-1261|
|Sivachenko, Anna; Gordon, Hannah B; Kimball, Suzanne S et al. (2016) Neurodegeneration in a Drosophila model of adrenoleukodystrophy: the roles of the Bubblegum and Double bubble acyl-CoA synthetases. Dis Model Mech 9:377-87|
|Tianero, Ma Diarey; Pierce, Elizabeth; Raghuraman, Shrinivasan et al. (2016) Metabolic model for diversity-generating biosynthesis. Proc Natl Acad Sci U S A 113:1772-7|
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