Abstract

Critical illness syndromes, such as acute respiratory distress syndrome (ARDS), septic shock, myocardial depression, and multiple organ failure all share the hypothesis that the host response plays a central pathogenic role. In this project, CCMD has established the infrastructure necessary to define these pathogenic host responses at the level of gene expression across thousands of mRNA transcripts, simultaneously. This technology will be used to create a large critical illness functional genomics database using in vitro models, small animal (rat and mouse) models, endotoxin-challenged volunteers, and ultimately critically ill patients. Preliminary work has identified more than 350 genes that are differentially regulated by the administration of endotoxin to healthy volunteers. Bacterial challenge in rats has shown that a number of genes are expressed in a graded manner that corresponds closely to infection severity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Intramural Research (Z01)
Project #
1Z01CL001164-03
Application #
6683786
Study Section
(CCM)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2002
Total Cost
Indirect Cost

  Institution

Name
Clinical Center
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Deans, Katherine J; Minneci, Peter C; Chen, Hao et al. (2009) Impact of animal strain on gene expression in a rat model of acute cardiac rejection. BMC Genomics 10:280
Raghavachari, Nalini; Xu, Xiuli; Harris, Amy et al. (2007) Amplified expression profiling of platelet transcriptome reveals changes in arginine metabolic pathways in patients with sickle cell disease. Circulation 115:1551-62
Elshal, Mohamed F; Khan, Sameena S; Raghavachari, Nalini et al. (2007) A unique population of effector memory lymphocytes identified by CD146 having a distinct immunophenotypic and genomic profile. BMC Immunol 8:29
Oliveira, Joao B; Bidere, Nicolas; Niemela, Julie E et al. (2007) NRAS mutation causes a human autoimmune lymphoproliferative syndrome. Proc Natl Acad Sci U S A 104:8953-8
Ptasinska, Anetta; Wang, Shuibang; Zhang, Jianhua et al. (2007) Nitric oxide activation of peroxisome proliferator-activated receptor gamma through a p38 MAPK signaling pathway. FASEB J 21:950-61
Goh, Sung-Ho; Josleyn, Matthew; Lee, Y Terry et al. (2007) The human reticulocyte transcriptome. Physiol Genomics 30:172-8
Zhang, Qian; Yu, Yong A; Wang, Ena et al. (2007) Eradication of solid human breast tumors in nude mice with an intravenously injected light-emitting oncolytic vaccinia virus. Cancer Res 67:10038-46
Zhang, Jianhua; Wang, Shuibang; Kern, Steven et al. (2007) Nitric oxide down-regulates polo-like kinase 1 through a proximal promoter cell cycle gene homology region. J Biol Chem 282:1003-9
Talwar, Shefali; Munson, Peter J; Barb, Jennifer et al. (2006) Gene expression profiles of peripheral blood leukocytes after endotoxin challenge in humans. Physiol Genomics 25:203-15
Wang, Shuibang; Zhang, Jianhua; Theel, Stephanie et al. (2006) Nitric oxide activation of Erk1/2 regulates the stability and translation of mRNA transcripts containing CU-rich elements. Nucleic Acids Res 34:3044-56

Showing the most recent 10 out of 13 publications