? Metabolomics Core Based on the success of the Cancer Metabolism Developing Shared Resource and growing scientific needs of ACC members, the ACC established the Metabolomics Core as a full-fledged Shared Resource, with an expanded array of services. Dr. Daniel Kelly, Ware Professor of Diabetes and Metabolic Diseases, has assumed leadership of this Shared Resource. Dr. Kelly is a well-recognized expert in mitochondrial metabolism and leader in the study of the metabolic origins of diseases in his over 25-year career. This new Shared Resource is staffed by Technical Director Dr. Christopher Petucci, along with a fully trained analytical chemist. Dr. Petucci has over 20 years of experience in mass spectrometry, including extensive expertise in measuring metabolites in cells, biological fluids, and tissues from animals and humans. The Metabolomics Core provides critically needed state-of-the-art targeted and untargeted metabolomics and lipidomics services to ACC researchers, which are extremely cost-effective compared to the out-sourcing used in the past. The Metabolomics Core: 1) provides well-validated, quantitative, targeted liquid chromatography-mass spectrometry (LC/MS) metabolomics of 127 metabolites from samples including cells, plasma, and tissues; 2) provides untargeted metabolomics and lipidomics platforms, for metabolite and lipid discovery; 3) performs LC/MS method development for custom metabolite assays tailored to individual needs; and 4) provides education and training in the use of the these technologies. The Metabolomics Core has four triple quadrupole mass spectrometers, two high resolution instruments (one for metabolomics and lipidomics, and one for protein quantification), Agilent 1290 Infinity HPLC and 6495B triple quadrupole mass spectrometers for targeted metabolomics and a Thermo Fisher Scientific UHPLC/Orbitrap ID-X mass spectrometer for untargeted metabolomics and lipidomics. ACC members accounted for 26 of 56 investigators (46%) using the Shared Resource during the most recent reporting period (07/01/18-06/30/19). As one example of high impact research dependent upon the Metabolomics Core Shared Resource, Dr. Carl June (Immunobiology) evaluated the attributes of CAR costimulatory domains and demonstrated that CAR-T cells with 4-1BB coreceptors increase respiratory capacity, fatty acid oxidation and mitochondrial biogenesis, in contrast to CAR-T cells with CD28 coreceptors which had metabolomics consistent with enhanced glycolysis in effector memory cells (Kawalekar et al., Immunity, 2016), which has already impacted clinical trial design. The Metabolomics Core is supported by the ACC in partnership with Penn's Cardiovascular Institute and the Institute for Diabetes, Obesity and Metabolism. The mission of the Metabolomics Core is to provide ACC members with a world-class platform providing new discoveries and insight into cellular metabolic mechanisms, which can be integrated with genetics, epigenetics, cell signaling, and other molecular bases of cancer.
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