The human metabolome represents the functional display of the human genome and proteome. The regulation of its homeostasis is highly sensitive to both intrinsic and external factors, the perturbation of which can lead to disease development. Advances in mass spectrometry (MS), NMR, informatics, and sample processing have made possible large-scale interrogation of the human metabolome ("metabolomics") and is being increasingly applied to a variety of diseases, such as cancer, diabetes, neurodegenerative and cardiovascular disorders, for diagnosis and therapeutic purposes. The existing Center for Regulatory and Environmental Analytical Metabolomics (CREAM) conducts training and provides advice and full analytical resources, from sample processing, MS and NMR instrumentation, to informatics, which match with the major goals of the Common Fund. Moreover, CREAM is now in its 6th year of self- sufficiency through client fees and conducts translational clinical research, both of which are critical fifth-year exit goals of the Common Fund. Building on this solid foundation with added resources, the proposed Common Fund Regional Comprehensive Metabolomics Resource Core (RCMRC) at the University of Louisville will greatly expand CREAM's capabilities in sample processing, analytical/informatics developments and services, and outreach efforts under the leadership of the PD and Pis, who collectively have more than 95 years of experience in metabolomics. The Overall Goals of the RCMRC-CREAM 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, model animals, to human subjects, and to provide the state-of-art analytical and informatics resources, education, and training for the biomedical research community. These goals will be achieved via the following specific aims: SA1: To administer comprehensive Metabolomics resources for bench to bedside research;SA2: To develop and implement integrated Metabolomics platforms to enhance performance, sample &information throughput, and scientific relevance;SA3: To provide outreach and education of the wider community in Metabolomics approaches.
It is increasingly recognized that perturbations to the human metabolome is crucial to the development and therapeutic outcome of many major, intractable diseases. The integrated metabolomic technologies and outreach efforts offered by the proposed RCMRC-CREAM will help promote adoption of metabolomic approaches in basic and translational biomedical research, thereby accelerating our ability to prevent and diagnose diseases as well as to uncover novel therapeutic targets.
|Li, Jing; Song, Jun; Zaytseva, Yekaterina Y et al. (2016) An obligatory role for neurotensin in high-fat-diet-induced obesity. Nature 533:411-5|
|Lane, Andrew N; Higashi, Richard M; Fan, Teresa W-M (2016) Preclinical models for interrogating drug action in human cancers using Stable Isotope Resolved Metabolomics (SIRM). Metabolomics 12:|
|Saxena, Neetu; Maio, Nunziata; Crooks, Daniel R et al. (2016) SDHB-Deficient Cancers: The Role of Mutations That Impair Iron Sulfur Cluster Delivery. J Natl Cancer Inst 108:|
|Sud, Manish; Fahy, Eoin; Cotter, Dawn et al. (2016) Metabolomics Workbench: An international repository for metabolomics data and metadata, metabolite standards, protocols, tutorials and training, and analysis tools. Nucleic Acids Res 44:D463-70|
|Fan, Teresa W-M; Lane, Andrew N (2016) Applications of NMR spectroscopy to systems biochemistry. Prog Nucl Magn Reson Spectrosc 92-93:18-53|
|Fan, Teresa W-M; Lane, Andrew N; Higashi, Richard M (2016) Stable Isotope Resolved Metabolomics Studies in Ex Vivo TIssue Slices. Bio Protoc 6:|
|Lane, Andrew N; Arumugam, Sengodagounder; Lorkiewicz, Pawel K et al. (2015) Chemoselective detection and discrimination of carbonyl-containing compounds in metabolite mixtures by 1H-detected 15N nuclear magnetic resonance. Magn Reson Chem 53:337-43|
|Liu, Min; Luo, Fengling; Ding, Chuanlin et al. (2015) Dectin-1 Activation by a Natural Product Î²-Glucan Converts Immunosuppressive Macrophages into an M1-like Phenotype. J Immunol 195:5055-65|
|Tarrado-Castellarnau, MÃriam; CortÃ©s, RoldÃ¡n; Zanuy, Miriam et al. (2015) Methylseleninic acid promotes antitumour effects via nuclear FOXO3a translocation through Akt inhibition. Pharmacol Res 102:218-34|
|Sellers, Katherine; Fox, Matthew P; Bousamra 2nd, Michael et al. (2015) Pyruvate carboxylase is critical for non-small-cell lung cancer proliferation. J Clin Invest 125:687-98|
Showing the most recent 10 out of 16 publications