Currently, there is no effective pharmacologic therapy against ARDS because of insufficient knowledge of the pathogenesis mechanisms. The overarching focus of the P01 is on mechanisms of pulmonary responses to a new pulmonary toxin and regulator, the anionic phosholipid, cardiolipin (CL) originating from bacteria or mitochondria of damaged host cells during acute lung injury. Thus elucidation of novel metabolic and biochemical pathways of different molecular species of CL, its metabolites and their interactions with other pulmonary lipids and their peroxidation products are fundamental to all four projects of the P01. The Oxidative Lipidomics Core (Core B) has been designed to allow researchers in the projects to perform detailed analysis - identification, characterization and imaging - of all major molecular species of Cls, other different classes of lipids as well as their oxidation products. This will be achieved by using sophisticated state-of-the art techniques based on different versions of mass-spectrometry (MS) combined with liquid? chromatography (LC) or high-performance thin-layer chromatography (HPTLC) protocols.
Specific Aims of the Oxidative Lipidomics Core B are to: 1. Provide professional expertise in the design and implementation of experiments using adequate techniques for identification, characterization, and quantification of lipids, particularly Cls. Prepare and optimally analyze samples to detect individual molecular species of lipids and oxidized lipids. 2. Provide opportunities for mass-spectrometric imaging of different types of individual molecular species and oxidized lipids in lung tissues. 3. Evaluate experimental results and propose subsequent experimental direction. 4. Provide training in the use of and access to any instrumentations and techniques used within the P01 project to assess lipidomics/oxidative lipidomics biomarkers. By assisting the Projects in the analytical work, the Core will facilitate studies of the mechanisms through which CL functions as a new molecular signal in acute lung injury hence contributes to the development of new therapeutic modalities.

Public Health Relevance

The goal of this PPG is to characterize a newly discovered damage signal, cardiolipin (CL), in acute lung injury, The Oxidative Lipidomics Core will perform state-of-the art analysis of all major molecular species of Cls in pulmonary cells and lung tissue. The analytical work of the Core will facilitate the discovery of the new mechanisms of acute lung injury hence contribute to the development of innovative therapeutic modalities

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Heart, Lung, and Blood Initial Review Group (HLBP)
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University of Pittsburgh
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McKelvey, Alison C; Lear, Travis B; Dunn, Sarah R et al. (2016) RING finger E3 ligase PPP1R11 regulates TLR2 signaling and innate immunity. Elife 5:
Nan, Ling; Jacko, Anastasia M; Tan, Jiangning et al. (2016) Ubiquitin carboxyl-terminal hydrolase-L5 promotes TGFβ-1 signaling by de-ubiquitinating and stabilizing Smad2/Smad3 in pulmonary fibrosis. Sci Rep 6:33116
Liu, Yuan; Mallampalli, Rama K (2016) Small molecule therapeutics targeting F-box proteins in cancer. Semin Cancer Biol 36:105-19
Lear, Travis; McKelvey, Alison C; Rajbhandari, Shristi et al. (2016) Ubiquitin E3 ligase FIEL1 regulates fibrotic lung injury through SUMO-E3 ligase PIAS4. J Exp Med 213:1029-46
Harris, Leonard A; Hogg, Justin S; Tapia, José-Juan et al. (2016) BioNetGen 2.2: advances in rule-based modeling. Bioinformatics 32:3366-3368
Morel, Penelope A; Lee, Robin E C; Faeder, James R (2016) Demystifying the cytokine network: Mathematical models point the way. Cytokine :
Singamsetty, Srikanth; Shah, Faraaz Ali; Guo, Lanping et al. (2016) Early initiation of low-level parenteral dextrose induces an accelerated diabetic phenotype in septic C57BL/6J mice. Appl Physiol Nutr Metab 41:12-9
Mao, Gaowei; Qu, Feng; St Croix, Claudette M et al. (2016) Mitochondrial Redox Opto-Lipidomics Reveals Mono-Oxygenated Cardiolipins as Pro-Apoptotic Death Signals. ACS Chem Biol 11:530-40
Tejero, Jesús; Kapralov, Alexandr A; Baumgartner, Matthew P et al. (2016) Peroxidase activation of cytoglobin by anionic phospholipids: Mechanisms and consequences. Biochim Biophys Acta 1861:391-401
Buland, Justin R; Wasserloos, Karla J; Tyurin, Vladimir A et al. (2016) Biosynthesis of oxidized lipid mediators via lipoprotein-associated phospholipase A2 hydrolysis of extracellular cardiolipin induces endothelial toxicity. Am J Physiol Lung Cell Mol Physiol 311:L303-16

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