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.
|Zaytseva, Yekaterina Y; Rychahou, Piotr G; Le, Anh-Thu et al. (2018) Preclinical evaluation of novel fatty acid synthase inhibitors in primary colorectal cancer cells and a patient-derived xenograft model of colorectal cancer. Oncotarget 9:24787-24800|
|Crooks, Daniel R; Maio, Nunziata; Lane, Andrew N et al. (2018) Acute loss of iron-sulfur clusters results in metabolic reprogramming and generation of lipid droplets in mammalian cells. J Biol Chem 293:8297-8311|
|Lian, Gaojian; Gnanaprakasam, Jn Rashida; Wang, Tingting et al. (2018) Glutathione de novo synthesis but not recycling process coordinates with glutamine catabolism to control redox homeostasis and directs murine T cell differentiation. Elife 7:|
|Sun, Ramon C; Fan, Teresa W-M; Deng, Pan et al. (2017) Noninvasive liquid diet delivery of stable isotopes into mouse models for deep metabolic network tracing. Nat Commun 8:1646|
|Wang, Qingding; Zhou, Yuning; Rychahou, Piotr et al. (2017) Ketogenesis contributes to intestinal cell differentiation. Cell Death Differ 24:458-468|
|Yang, Ye; Fan, Teresa W-M; Lane, Andrew N et al. (2017) Chloroformate derivatization for tracing the fate of Amino acids in cells and tissues by multiple stable isotope resolved metabolomics (mSIRM). Anal Chim Acta 976:63-73|
|Yao, Sen; Flight, Robert M; Rouchka, Eric C et al. (2017) Perspectives and expectations in structural bioinformatics of metalloproteins. Proteins 85:938-944|
|Salem, Shaimaa M; Weidenbach, Stevi; Rohr, Jürgen (2017) Two Cooperative Glycosyltransferases Are Responsible for the Sugar Diversity of Saquayamycins Isolated from Streptomyces sp. KY 40-1. ACS Chem Biol 12:2529-2534|
|Yao, Sen; Flight, Robert M; Rouchka, Eric C et al. (2017) Aberrant coordination geometries discovered in the most abundant metalloproteins. Proteins 85:885-907|
|Matrka, Marie C; Watanabe, Miki; Muraleedharan, Ranjithmenon et al. (2017) Overexpression of the human DEK oncogene reprograms cellular metabolism and promotes glycolysis. PLoS One 12:e0177952|
Showing the most recent 10 out of 32 publications