The overall goal of the proposal, """"""""Expression Analysis to Study Disease Pathogenesis"""""""" is to provide state of the art expression analysis and bioinformatic services for researchers engaged in scientific studies of cardiac, pulmonary, hematological, and sleep disorders. This RFA application augments our current Facility's service to NHLBI researchers in four ways: 1) By economies of scale, we can provide cost-effective expression array analysis using either our in-house spotted cDNA arrays or Affymetrix GeneChips, 2) The RFA enables a focused and directed educational experience for NHLBI researchers in all aspects of expression technology, including data analysis, 3) The mechanism would provide our Facility with funding for critical developmental projects aimed at maximizing accuracy in new techniques, and 4) Our bioinformatics group could develop a highly useful analysis tool (Internet-based) encompassing both data analysis and maps to relevant databases and biomedical literature with a focus on heart, lung, blood, and sleep disorders. Given this background, the Specific Aims of the Facility are as follows:
Specific Aim 1 : To provide excellence in gene expression analysis for NHLBI researchers. The revolution in genomic research has included the ability to perform large-scale expression analysis to analyze greater patterns of gene expression changes. The application of this technology is broad-based and can include hypothesis-driven research, as well as hypothesis generating experiments.
Specific Aim 2 : To perform developmental projects for a. maximizing RNA amplification techniques, and b. utilizing reference standards and strategies to develop algorithms for direct comparison of data from cDNA arrays and Affymetrix arrays.
Specific Aim 3 : To develop and implement comprehensive bioinformatic approaches to expression data analysis, including """"""""scripted"""""""", Internet-based analysis for NHLBI researchers. The bioinformatics approach is to be utilized in the current proposal will 1) model the range of normality within given systems, 2) develop methods for determining coordination in expression data, and 3) provide models for the discrimination between sets of genes.
Specific Aim 3 is designed to provide NHLBI researchers with a user-friendly, powerful Internet-based analysis tool. This tool will be specific for the needs of researchers in heart, lung, blood and sleep-related fields.
| Stearman, Robert S; Dwyer-Nield, Lori; Grady, Michael C et al. (2008) A macrophage gene expression signature defines a field effect in the lung tumor microenvironment. Cancer Res 68:34-43 |
| Yang, Hyuna; Harrington, Christina A; Vartanian, Kristina et al. (2008) Randomization in laboratory procedure is key to obtaining reproducible microarray results. PLoS One 3:e3724 |
| Coldren, Christopher D; Nick, Jerry A; Poch, Katie R et al. (2006) Functional and genomic changes induced by alveolar transmigration in human neutrophils. Am J Physiol Lung Cell Mol Physiol 291:L1267-76 |
| Gruber, Michael P; Coldren, Christopher D; Woolum, Malcolm D et al. (2006) Human lung project: evaluating variance of gene expression in the human lung. Am J Respir Cell Mol Biol 35:65-71 |
| Stearman, Robert S; Dwyer-Nield, Lori; Zerbe, Laura et al. (2005) Analysis of orthologous gene expression between human pulmonary adenocarcinoma and a carcinogen-induced murine model. Am J Pathol 167:1763-75 |
| Bull, Todd M; Coldren, Christopher D; Moore, Mark et al. (2004) Gene microarray analysis of peripheral blood cells in pulmonary arterial hypertension. Am J Respir Crit Care Med 170:911-9 |
| Golpon, Heiko A; Coldren, Christopher D; Zamora, Martin R et al. (2004) Emphysema lung tissue gene expression profiling. Am J Respir Cell Mol Biol 31:595-600 |
