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.
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.
|Huang, Long Shuang; Natarajan, Viswanathan (2015) Sphingolipids in pulmonary fibrosis. Adv Biol Regul 57:55-63|
|Ni, Xiuqin; Epshtein, Yulia; Chen, Weiguo et al. (2014) Interaction of integrin ?4 with S1P receptors in S1P- and HGF-induced endothelial barrier enhancement. J Cell Biochem 115:1187-95|
|Wolfson, Rachel K; Mapes, Brandon; Garcia, Joe G N (2014) Excessive mechanical stress increases HMGB1 expression in human lung microvascular endothelial cells via STAT3. Microvasc Res 92:50-5|
|Chen, Jiwang; Tang, Haiyang; Sysol, Justin R et al. (2014) The sphingosine kinase 1/sphingosine-1-phosphate pathway in pulmonary arterial hypertension. Am J Respir Crit Care Med 190:1032-43|
|Testai, Fernando D; Kilkus, John P; Berdyshev, Evgeny et al. (2014) Multiple sphingolipid abnormalities following cerebral microendothelial hypoxia. J Neurochem 131:530-40|
|Usatyuk, Peter V; Fu, Panfeng; Mohan, Vijay et al. (2014) Role of c-Met/phosphatidylinositol 3-kinase (PI3k)/Akt signaling in hepatocyte growth factor (HGF)-mediated lamellipodia formation, reactive oxygen species (ROS) generation, and motility of lung endothelial cells. J Biol Chem 289:13476-91|
|Adyshev, Djanybek M; Elangovan, Venkateswaran Ramamoorthi; Moldobaeva, Nurgul et al. (2014) Mechanical stress induces pre-B-cell colony-enhancing factor/NAMPT expression via epigenetic regulation by miR-374a and miR-568 in human lung endothelium. Am J Respir Cell Mol Biol 50:409-18|
|Huang, Long Shuang; Mathew, Biji; Li, Haiquan et al. (2014) The mitochondrial cardiolipin remodeling enzyme lysocardiolipin acyltransferase is a novel target in pulmonary fibrosis. Am J Respir Crit Care Med 189:1402-15|
|Wang, Lichun; Sammani, Saad; Moreno-Vinasco, Liliana et al. (2014) FTY720 (s)-phosphonate preserves sphingosine 1-phosphate receptor 1 expression and exhibits superior barrier protection to FTY720 in acute lung injury. Crit Care Med 42:e189-99|
|Makarenko, Vladislav V; Usatyuk, Peter V; Yuan, Guoxiang et al. (2014) Intermittent hypoxia-induced endothelial barrier dysfunction requires ROS-dependent MAP kinase activation. Am J Physiol Cell Physiol 306:C745-52|
Showing the most recent 10 out of 25 publications