Human Tissues, Lipidomics, and Proteomics Core

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SUMMARY – HUMAN TISSUES, LIPOPROTEINS, LIPIDOMICS, & PROTEOMICS CORE (C2) The Human Tissues, Lipoproteins, Lipidomics, and Proteomics Core (Core 2, C2) will focus on providing human tissues and analytical capabilities to all three projects to enhance translatability of mouse studies proposed in P1–P3 to clinical practice in humans. In parallel, Core 2 will provide lipoprotein, lipidomic, and proteomic analyses currently not provided by our institutional Metabolomics Core. The cardiovascular research community has shown many important correlations between clinical outcomes and the plasma levels of atherogenic particles of different densities, as determined by ultracentrifugation. More detailed analyses are now uncovering additional risk for cardiovascular disease (CVD) within these particles, such as the content of apoC3 and ceramides. For this PPG, Core 2 will provide a more granular analysis of lipoproteins isolated by centrifugation and size exclusion chromatography through both directed and unbiased lipidomic and proteomic analyses of these particles. In addition, clinical samples (sera, liver, adipose) obtained by the core director will be provided to investigators in all three projects. These services will avoid the need for PPG investigators to maintain the required instrumentation in their own laboratories or use expensive commercial services. By centralizing and standardizing procedures, Core 2 provides a common set of analytical tools to provide a unified understanding of molecular mechanisms involved in pathophysiologic processes of atherosclerosis, macrophage biology, regulation of triglyceride-rich lipoproteins, and obesity. By complementing and integrating with the service provided by Core 1, Core 2 staff also provide bioinformatics support to analyze and interpret proteomic and lipidomic data sets, making Core 2 capabilities available to PPG investigators with little background or expertise in these analytical technologies. A key long-term goal is to integrate quantitative analyses of lipidomic data with functional studies to provide a systems biology view of diabetes-related cardiovascular disease. Core 2 will also develop new analytical methods tailored to specific research objectives of PPG investigators. Specifically, we will obtain and use standards to quantify and discover candidate lipids whose role in atherosclerosis is being investigated. These methods will be extensively used by PPG investigators. Core 2 will offer these services with optimal efficiency and cost-effectiveness, avoiding the need for individuals to pursue such analyses outside the PPG.