Metabolomics requires identification and quantification of a large number of metabolites of many different biochemical classes, from diverse biological samples, including cells, culture media, tissue and biofluids. Where biochemical mechanism is desired, it is imperative that metabolomic approach be coupled with stable isotope (e.g. 0-13, or N-15) tracer labeling for robust metabolic network reconstruction, which increase the number of analytes to be determined by orders of magnitude. The goals of the Analytical Core of the RCMRC-CREAM are to provide analytical services for a wide coverage of metabolites, including isotopomer and isotopologue analysis as efficiently as possible. To achieve this, we use of a number of analytical platforms including high-resolution mass spectrometry with or without liquid chromatography, gas. chromatography MS, high resolution and in vivo NMR. The Core will continue to develop and implement improved methods of data collection and reduction to increase the overall metabolite coverage and analytical throughput. These include 1) upgrade existing and install new high throughput instrumentation dedicated to metabolomics;2) incorporate chemoselective tagging approach for improved metabolite coverage and assignment. The Core will continue to update its databases and refines its standard operating procedures. The Core will consult with users on experimental design, analytical methods, and additional technologies that may be needed to identify and quantify "unknowns" that appear to be biologically important. The Analytical Core thus works closely with the Sample and the Informatics Cores to achieve these goals by the following Specific Aims. SA1. To provide access and expertise across a wide range of NMR and MS technologies to the Clients. SA2. To provide data processing support to the Clients, in coordination with the Informatics Core for statistical analysis, metabolic pathway, and biochemical mechanism analyses. SA3. To implement additional hardware capabilities for enhanced sample throughput. SA4. To develop and implement new methods to enhance metabolomic capabilities.
The Analytical Core serves the vital function of large-scale metabolite analyses to promote metabolomic research in biomedical community. In particular, stable isotope-resolved metabolomic data procured by the Core will facilitate systems biochemical understanding of human diseases for the purpose of diagnosis, prognosis, therapeutics, and response to therapeutic interventions.
|Xie, Han; Hanai, Jun-Ichi; Ren, Jian-Guo et al. (2014) Targeting lactate dehydrogenase--a inhibits tumorigenesis and tumor progression in mouse models of lung cancer and impacts tumor-initiating cells. Cell Metab 19:795-809|