This Genome-Wide Application Core (GWAC) will provide essential, cutting edge, genomic and genetic expertise to facilitate the translational impact of this highly integrated PPG. The overall objective of Core D is to provide: A) Well characterized sepsis-induced acute lung injury (ALI) and radiation-induced lung injury (RILI) cohorts of African- and European-Americans populations);B) Biological specimens (DNA, RNA, serum, and plasma) from two ethnic groups;C) A list of molecular signatures and novel candidate genes involved in ALI and RILI;D) A complete list of tagging single nucleotide polymorphisms (tSNPs) for each candidate gene involved in SIP biosynthetic/signaling pathway;E). Mid-throughput Affymetrix microarray techniques and genotyping services;and F). Genomic and genetic data analytical services to identify differentially regulated candidate genes and to test for association with susceptibility and severity of ALI or RILI. The GWAC Core will interact with all 4 Projects: 1) providing Project #1 the association study results involving sphingosine kinase and SIP lyase candidate genes and ALI. 2) providing Project #2 with a well characterized phenotype database and bio-bank (i.e. DNA, RNA, serum, plasma) on ALI cohort and an overall list of tSNPs selection of candidate genes involved in S1P biosynthesis/signaling pathway; genotyping services, case-control association data analysis 3) providing Project #3 with the genomic signatures on SI P or FTY720- or SEW-mediated LPS-induced ALI in human endothelial cells, as well as in genetically engineered mice (e.g. SI PI -/+, SI P3-/-) using microarray technology 4) providing Project #4 with a well characterized database and bio-bank on RILI cohort;association behween potential biomarkers in the serum/plasma level with genotype and SNP-specific association studies in RILI of the SIP biosynthetic pathway as well as molecular signatures in mouse whole lung tissue in response to radiation over time particularly focused on sphingolipids and related signaling.

Public Health Relevance

Core D will facilitate translational research on Genomic assessment and Genetic analysis of total RNA from lung tissues or cell cultures of ALI and RILI. For Genetic application, GWAC will be responsible for providing investigators with a well characterized ALI and RILI bio-bank for the two etnic groups (European American and African American), a complete list of taggimng SNPs for each of the candidate gene involved in S1P biosynthesis pathway.

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 Illinois at Chicago
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Ackerman, Steven J; Park, Gye Young; Christman, John W et al. (2016) Polyunsaturated lysophosphatidic acid as a potential asthma biomarker. Biomark Med 10:123-35
Camp, Sara M; Chiang, Eddie T; Sun, Chaode et al. (2016) ""Pulmonary Endothelial Cell Barrier Enhancement by Novel FTY720 Analogs: Methoxy-FTY720, Fluoro-FTY720, and β-Glucuronide-FTY720"". Chem Phys Lipids 194:85-93
Ebenezer, David L; Fu, Panfeng; Natarajan, Viswanathan (2016) Targeting sphingosine-1-phosphate signaling in lung diseases. Pharmacol Ther 168:143-157
Viswanathan, P; Ephstein, Y; Garcia, J G N et al. (2016) Differential elastic responses to barrier-altering agonists in two types of human lung endothelium. Biochem Biophys Res Commun 478:599-605
Black, Katharine E; Berdyshev, Evgeny; Bain, Gretchen et al. (2016) Autotaxin activity increases locally following lung injury, but is not required for pulmonary lysophosphatidic acid production or fibrosis. FASEB J 30:2435-50
Ebenezer, David L; Fu, Panfeng; Suryadevara, Vidyani et al. (2016) Epigenetic regulation of pro-inflammatory cytokine secretion by sphingosine 1-phosphate (S1P) in acute lung injury: Role of S1P lyase. Adv Biol Regul :
Jiang, Ying; Sverdlov, Maria S; Toth, Peter T et al. (2016) Phosphatidic Acid Produced by RalA-activated PLD2 Stimulates Caveolae-mediated Endocytosis and Trafficking in Endothelial Cells. J Biol Chem 291:20729-38
Zhang, Chongben; Hwarng, Gwen; Cooper, Daniel E et al. (2015) Inhibited insulin signaling in mouse hepatocytes is associated with increased phosphatidic acid but not diacylglycerol. J Biol Chem 290:3519-28
Huang, Long Shuang; Berdyshev, Evgeny V; Tran, John T et al. (2015) Sphingosine-1-phosphate lyase is an endogenous suppressor of pulmonary fibrosis: role of S1P signalling and autophagy. Thorax 70:1138-48
Letsiou, Eleftheria; Sammani, Saad; Zhang, Wei et al. (2015) Pathologic mechanical stress and endotoxin exposure increases lung endothelial microparticle shedding. Am J Respir Cell Mol Biol 52:193-204

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