The Stable Isotope Resolved (SIRM) Analytical Shared Core will provide high information throughput (HIT) bioanalytical support for the groups, with special emphasis on stable isotope-based metabolic pathway tracing. The basis for this Core already exists in the form of the NSF-initiated, UofL Center for Regulatory and Environmental Analytical Metabolomics (CREAM), established expressly for SIRM metabolomic bioanalytical services and collaborations on sample preparation and handling, high field NMR, mass spectrometry, and biochemoinformatics since 2002. CREAM houses state of the art instrumentation that has profoundly influenced experimental design for several research groups. Therefore, many Core interactions are by their nature long-standing, collaborative efforts. The main goals of the SIRM Shared Core are to provide a set of shared resources for all three Research Projects and seamlessly integrate experimental design, data collection, and data analysis spanning tissue culture, mouse models and human subjects. The Core will provide a combination of experimental methods to determine metabolic phenotypes of cancerous and non-cancerous lung cells and tissue using our state of the art analytical platforms in both NMR and mass spectrometry. In consultation with individual project leaders, specific experimental design for stable isotope analysis will be tailored to individual project needs, but with consistency across projects to facilitate integrated analyses. We have 3 specific aims to achieve our goals:
Specific Aim 1. Provide infrastructure and expert sample handling that ensures consistent handling, processing, and archiving of samples across all three Research Projects;
Specific Aim 2. Provide access and expertise across a wide range of NMR and MS technologies to the three Research Projects: A) Provide access to instrumentation and expertise for robust and consistent SIRM-based analytical experimental design and B) Provide expert data collection and analysis across a wide range of NMR and MS technologies.
Specific Aim 3. Provide data analytical support to the Research Projects, including data, metabolic pathway, and biochemical mechanism analyses, that include: A) Implement a web-based platform for data reduction, quality control and data analytical support;B) Provide methodologies for identifying and quantifying metabolites;C) Provide a bridge between the Projects, data acquisition and biochemical analysis in Gore A. Core B provides extensive interoperability, handling and advising all aspects of sample preparation, data collection, data analysis &quality control, ensuring consistency of data across all 3 research projects.

Public Health Relevance

Deaths from lung cancer are the highest among all cancers in North America and cure rates remain low. We seek to gain a deeper understanding of lung cancer biochemistry using a novel approach we developed. Improved knowledge will have direct impact on early diagnosis and prognosis. The biochemical differences between lung cancer subtypes can be related to appropriate treatments.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
7P01CA163223-02
Application #
8744926
Study Section
Special Emphasis Panel (ZCA1-RPRB-0)
Project Start
2014-08-19
Project End
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
2
Fiscal Year
2014
Total Cost
$308,521
Indirect Cost
$78,146
Name
University of Kentucky
Department
Type
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506
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
Lane, Andrew N; Fan, Teresa W-M (2017) NMR-based Stable Isotope Resolved Metabolomics in systems biochemistry. Arch Biochem Biophys 628:123-131
Yan, J (2017) Identifying biomarkers in human psoriasis: revealed by a systems metabolomics approach. Br J Dermatol 176:555-557
Zhao, Jiangsha; Li, Jieran; Fan, Teresa W M et al. (2017) Glycolytic reprogramming through PCK2 regulates tumor initiation of prostate cancer cells. Oncotarget 8:83602-83618
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
Bruntz, Ronald C; Lane, Andrew N; Higashi, Richard M et al. (2017) Exploring cancer metabolism using stable isotope-resolved metabolomics (SIRM). J Biol Chem 292:11601-11609
Fan, Teresa W-M; Warmoes, Marc O; Sun, Qiushi et al. (2016) Distinctly perturbed metabolic networks underlie differential tumor tissue damages induced by immune modulator ?-glucan in a two-case ex vivo non-small-cell lung cancer study. Cold Spring Harb Mol Case Stud 2:a000893
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:
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
Albeituni, Sabrin H; Ding, Chuanlin; Liu, Min et al. (2016) Yeast-Derived Particulate ?-Glucan Treatment Subverts the Suppression of Myeloid-Derived Suppressor Cells (MDSC) by Inducing Polymorphonuclear MDSC Apoptosis and Monocytic MDSC Differentiation to APC in Cancer. J Immunol 196:2167-80

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