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

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
1P01HL114453-01A1
Application #
8643333
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
2014-01-03
Project End
2018-12-31
Budget Start
2014-01-03
Budget End
2014-12-31
Support Year
1
Fiscal Year
2014
Total Cost
$201,349
Indirect Cost
$69,963
Name
University of Pittsburgh
Department
Type
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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