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.
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
|Suber, Tomeka L; Nikolli, Ina; O'Brien, Michael E et al. (2018) FBXO17 promotes cell proliferation through activation of Akt in lung adenocarcinoma cells. Respir Res 19:206|
|Kitsios, Georgios D; Fitch, Adam; Manatakis, Dimitris V et al. (2018) Respiratory Microbiome Profiling for Etiologic Diagnosis of Pneumonia in Mechanically Ventilated Patients. Front Microbiol 9:1413|
|Chao, Honglu; Anthonymuthu, Tamil S; Kenny, Elizabeth M et al. (2018) Disentangling oxidation/hydrolysis reactions of brain mitochondrial cardiolipins in pathogenesis of traumatic injury. JCI Insight 3:|
|Kitsios, Georgios D; McVerry, Bryan J (2018) Host-Microbiome Interactions in the Subglottic Space. Bacteria Ante Portas! Am J Respir Crit Care Med 198:294-297|
|Lou, Wenjia; Ting, Hsiu-Chi; Reynolds, Christian A et al. (2018) Genetic re-engineering of polyunsaturated phospholipid profile of Saccharomyces cerevisiae identifies a novel role for Cld1 in mitigating the effects of cardiolipin peroxidation. Biochim Biophys Acta Mol Cell Biol Lipids 1863:1354-1368|
|Anthonymuthu, Tamil S; Kenny, Elizabeth M; Lamade, Andrew M et al. (2018) Oxidized phospholipid signaling in traumatic brain injury. Free Radic Biol Med 124:493-503|
|Hassannia, Behrouz; Wiernicki, Bartosz; Ingold, Irina et al. (2018) Nano-targeted induction of dual ferroptotic mechanisms eradicates high-risk neuroblastoma. J Clin Invest 128:3341-3355|
|Meiners, Silke; Evankovich, John; Mallampalli, Rama K (2018) The ubiquitin proteasome system as a potential therapeutic target for systemic sclerosis. Transl Res 198:17-28|
|Gaschler, Michael M; Andia, Alexander A; Liu, Hengrui et al. (2018) FINO2 initiates ferroptosis through GPX4 inactivation and iron oxidation. Nat Chem Biol 14:507-515|
|Qu, Yanyan; Olonisakin, Tolani; Bain, William et al. (2018) Thrombospondin-1 protects against pathogen-induced lung injury by limiting extracellular matrix proteolysis. JCI Insight 3:|
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