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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Special Emphasis Panel (ZCA1-RPRB-0)
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University of Kentucky
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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