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The Resource Center for Stable Isotope-Resolved Metabolomics (RC-SIRM) was established in 2013 at the University of Kentucky following the award of a NIH Regional Comprehensive Metabolomics Resource Cores grant (1U24DK097215-01A1), which is supported by the NIH Common Fund. Sister Centers and resources can be found at http://www.metabolomicsworkbench.org/.

This grant provided funds for the establishment of the Center by experts in the field and included funds for the purchase of state-of-the-art mass spectrometry and NMR spectrometers tailored for applications in stable isotope-resolved metabolomics (SIRM). The University of Kentucky also provided matching funds to support the establishment of this Center. The overall mission of the Center is to enable cutting-edge approaches and to provide state-of-the art instrumentation for SIRM, thus promoting fundamental and translational systems biochemical research in the life sciences.

Metabolism is the functional activity of all living cells, and thus this reflects the health status of an organism. Therefore the ability to measure global metabolism in quantitative detail is of fundamental importance in all aspects of biology. Metabolomics is the technical means to carry out global analyses of metabolism, via the ability to identify and quantify a large fraction of all of the metabolites present in a cell, and how they change in response to perturbations (1). This therefore requires high-end analytical instrumentation, of which mass spectrometry and NMR together are the most appropriate technologies (4-12). Issues of sample preparation (2,3) and data analysis/informatics (13-16) are similarly critically important and are specifically addressed in the Center. Furthermore, at RC-SIRM, a particular emphasis is on measurements of metabolic rates and changes by tracing individual atoms though metabolic pathways, via the agency of SIRM, an approach pioneered by the directors of RC-SIRM . Environmental factors come into play both at the extrinsic level (macroenvironment) as represented by diet and pollutants for example, and local environments (microenvironment) as represented by the prevailing tissue conditions outside cells.

The overall goals of the RC-SIRM are to facilitate and promote metabolomics research with an emphasis on stable isotope tracing for pathway elucidation in studies ranging from laboratory bench cell cultures (13,17), model animals (18,19,20), to human tissue and subjects (19-24), and to provide the state-of-art analytical and informatics resources, education, and training for the biomedical research community. The Center is further tasked with the development and implementation of new technologies to enhance throughput and coverage of metabolites (25-29). These goals are achieved by the following specific aims:
  1. Administer comprehensive metabolomics resources for bench to bedside research.
  2. Develop and implement integrated metabolomics platforms to enhance performance, sample & information throughput, and scientific relevance.
  3. Provide outreach and education of the wider community in metabolomics approaches.

References

  1. Fan, T.W.-M., R.M. Higashi, and A.N. Lane, eds. The Handbook of Metabolomics. Methods in Pharmacology and Toxicology, vol. 17. 2012, Humana: Totoya. DOI 10.1007/978-1-61779-618-0_9.
  2. Fan, T.W., Considerations of Sample Preparation for Metabolomics Investigation. Handbook of Metabolomics, 2012. 17(17).
  3. Fan, T.W.-M., Metabolomics-Edited Transcriptomics Analysis (Meta), in Comprehensive Toxicology, C.A. McQueen, Editor. 2010, Academic Press: Oxford. p. 685–706.
  4. Fan, T.W.-M. and A.N. Lane, Assignment strategies for NMR resonances in metabolomics research, in Methodologies for Metabolomics: Experimental Strategies and Techniques, N. Lutz, J.V. Sweedler, and R.A. Weevers, Editors. 2012, Cambridge University Press: Cambridge.
  5. Lane, A.N., NMR applications in metabolomics in Handbook of Metabolomics, T.W.-M. Fan, A.N. Lane, and R.M. Higashi, Editors. 2012, Humana.
  6. Fan, T.W.-M. and A.N. Lane, NMR-based Stable Isotope Resolved Metabolomics in Systems Biochemistry. J. Biomolec. NMR 2011. 49 p. 267–280
  7. Lane, A.N., T.W. Fan, and R.M. Higashi, Isotopomer-based metabolomic analysis by NMR and mass spectrometry. Biophysical Tools for Biologists. , 2008. 84: p. 541-588.
  8. Fan, T.W. and A.N. Lane, Structure-based profiling of Metabolites and Isotopomers by NMR. Progress in NMR Spectroscopy, 2008. 52: p. 69-117
  9. Lane, A.N. and T.W. Fan, Quantification and identification of isotopomer distributions of metabolites in crude cell extracts using 1H TOCSY. Metabolomics, 2007. 3: p. 79-86.
  10. Lane, A.N., T.W.-M. Fan, X. Xie, H.N. Moseley, and R.M. Higashi, Stable isotope analysis of lipid biosynthesis by high resolution mass spectrometry and NMR Anal. Chim. Acta, 2009. 651: p. 201-208.
  11. Higashi, R.M., Structural Mass Spectrometry for Metabolomics in Handbook of Metabolomics Methods, T.W. Fan, Higashi, R.M., Lane, A.N., Editor. 2011, Humana Press: New York.
  12. Higashi, R.M., T.W.-M. Fan, P.K. Lorkiewicz, H.N.B. Moseley, and A.N. Lane, Stable Isotope Labeled Tracers for Metabolic Pathway Elucidation by GC-MS and FT-MS, in Mass Spectrometry Methods in Metabolomics, D. Raftery, Editor. 2014, Humana Press USA.
  13. Moseley, H.N.B., A.N. Lane, A.C. Belshoff, R.M. Higashi, and T.W.-M. Fan, Non-Steady State Modeling of UDP-GlcNAc Biosynthesis is Enabled by Stable Isotope Resolved Metabolomics (SIRM) BMC Biology, 2011. 9: p. 37.
  14. Moseley, H.N.B., R.M. Higashi, T.W.-M. Fan, and A.N. Lane. Analysis of Non-Steady State Stable Isotope-Resolve Metabolism of UDP-GlcNAc and UDP-GalNAc. in Proceedings of Bioinformatics 2011. 2011. Rome, Italy: SciTePress, Portugal.
  15. Moseley, H., Correcting for the effects of natural abundance in stable isotope resolved metabolomics experiments involving ultra-high resolution mass spectrometry. BMC Bioinformatics, 2010. 11: p. 139.
  16. Moseley, H.N.B., Error Analysis and Propagation in Metabolomics Data Analysis. Computational and Structural Biotechnology Journal, 2013. 4: p. e301006
  17. Le, A., Lane, A.N., Hamaker, M., Bose, S., Barbi, J., Tsukamoto, T., Rojas, C.J., Slusher, B.S., Zhang, H., Zimmerman. L.J., Liebler, D.C., Slebos, R.J.C., Lorkiewicz, P.K., Higashi, R.M., Fan, T.W-M., and Dang, C.V. (2012) Myc induction of hypoxic glutamine metabolism and a glucose-independent TCA cycle in human B lymphocytes. Cell Metabolism. 15, 110-121
  18. Fan, T. W-M., Lane, A.N., Higashi, R.M., Yan, J. (2011) Stable Isotope Resolved Metabolomics of Lung Cancer in a SCID Mouse Model. Metabolomics 7, 257-269
  19. Lane, A.N., Fan, T. W-M., Bousamra II, M., Higashi, R.M., Yan, J., Miller, D.M. (2011) Stable Isotope-Resolved Metabolomics (SIRM) in Cancer Research with Clinical Application to Non-Small Cell Lung Cancer. Omics 15, 173-182
  20. Fan, T.W-M., Lorkiewicz, P., Sellers, K., Moseley, H.N.B., Higashi, R.M., Lane, A.N. (2012). Stable isotope-resolved metabolomics and applications to drug development. Pharmacology & Therapeutics. 133:366-391
  21. Fan, T.WM., Lane, A.N., Higashi, R.M., Farag, M.A., Gao, H., Bousamra, M. & Miller, D.M. (2009) Altered Regulation of Metabolic Pathways in Human Lung Cancer Discerned by 13C Stable Isotope-Resolved Metabolomics (SIRM). Molecular Cancer. 8:41
  22. Sellers, K., Fox, M.P., Bousamra, M., Slone, S., Higashi, R.M.,Miller, D.M., Wang, Y., Yan, J., Yuneva, M., Deshpande, R., Lane, A.N., Fan, T. W-M. (2015) Pyruvate carboxylase is upregulated in NSCLC. J Clin Invest. 125(2): 687-698

  23. Fan, T. W-M., Warmoes, M.O., Sun, Q., Song, H., Turchan-Cholewo, J., Martin, J.T., Mahan, A.L.,Higashi, R.M., Lane, A.N. (2016) Distinctly perturbed metabolic networks underlie differential tumor tissue damages induced by immune modulator beta-glucan in a two-case ex vivo non-small cell lung cancer study. CSH Molec. Case Studies 2, a000893

  24. Lane, A.N., Higashi, R.M. & Fan, T. W-M. (2016) Preclinical models for interrogating drug action in human cancers using Stable Isotope Resolved Metabolomics (SIRM) Metabolomics 12, 1-15

  25. Gori, S.S., Lorkiewicz, P., Ehringer, D.S., Belshoff, A.C., Higashi, R.M., Fan, T. W-M., and Nantz, M.H. (2014) Profiling Thiol Metabolites and Quantification of Cellular Glutathione using FT-ICR-MS Spectrometry. Analytical & Bioanalytical Chemistry 406, 4371-9
  26. Mitchell, J.M., Fan, T. W-M., Lane, A.N., Moseley, H.N.B. (2014) Informatics approaches to ‘omics systems integration Frontiers in Genetics (Systems Biology) 5, 237
  27. Lane, A.N., Arumugam, S., Lorkiewicz P.K., Higashi, R.M., Laulhe, S., Nantz, M.H., Moseley, H.N.B., Fan, T. W-M. (2015) Chemoselective detection of carbonyl compounds in metabolite mixtures by NMR. Mag Res Chem. 53, 337-343

  28. Fan, T. W-M. & Lane, A.N. (2016) Applications of NMR to Systems Biochemistry. Prog. NMR Spectrosc. 92,18-53

  29. Yang, Y., Fan, W. W-M., Lane, A.N. & Higashi, R.M. (2017) Chloroformate Derivatization for Tracing the Fate of Amino Acids in Cells by Multiple Stable Isotope Resolved Metabolomics (mSIRM). Anal. Chim. Acta 976, 63-73

Topic revision: r23 - 09 Jun 2017, AndrewLane
 

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