The overall goal of the Arthritis Genomics and Bioinformatics Core will be to support investigators in the? Program utilizing microarray techniques. The core will provide uniform sample preparation, microarray? design, data storage and bioinformatics, thus maximizing the reliability and compatibility of information? obtained across the Program. The Core will perform standardized RNA preparation from joint tissues of? experimental animals, and the amplification steps to generate labeled probe from small amounts of in vivo? or in vitro derived RNA. This should help to generate highly comparable datasets throughout the Program.? In addition, the Core will design a study-specific """"""""Arthritis Chip"""""""", with spotted oligonucleotides that? represent genes that vary during arthritogenesis. These custom chips will provide flexibility, allow a greater? throughput than would be economically feasible with whole-genome chips, and again enhance data? compatibility between the groups. The Core's bioinformatics personnel, which have acquired significant? experience in microarray analysis, will guide, train, and help investigators through data analysis in an open? and collaborative manner. The Core will provide access to basic analysis packages, and the ability to write? custom software in a data-driven manner, in response to particular experimental situations. In addition,? data analysis will benefit from a baseline of microarray data on gene expression during arthritis. A central? server for secure data storage will house copies of the data, and Web-based software for data browsing will? be applied as a Program-specific intranet and for public posting, as appropriate. In addition, the Core will? perform data mining on the assembled data, explorations made possible by the coordinated processing? and storage of the data, and by our pre-existing data on the evolution of gene expression in arthritic joints.? Cross-experiment analyses will search for gene-gene correlations and clusters throughout a variety of? conditions, and will generate functional gene hierarchies. These meta-analyses will enrich each of the? individual analyses: defining, for example, the subset of genes that are still induced in spite of a genetic? blockade of arthritis will help to pinpoint the cellular or functional level at which the gene is implicated. In? addition, the meta-analyses made possible by the combined and coordinated datasets will also provide a? unique insight into the """"""""arthritis genome"""""""".

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI065858-03
Application #
7666947
Study Section
Allergy & Clinical Immunology-1 (AITC)
Project Start
Project End
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
3
Fiscal Year
2008
Total Cost
$220,345
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Douaiher, Jeffrey; Succar, Julien; Lancerotto, Luca et al. (2014) Development of mast cells and importance of their tryptase and chymase serine proteases in inflammation and wound healing. Adv Immunol 122:211-52
Beckett, Emma L; Stevens, Richard L; Jarnicki, Andrew G et al. (2013) A new short-term mouse model of chronic obstructive pulmonary disease identifies a role for mast cell tryptase in pathogenesis. J Allergy Clin Immunol 131:752-62
Cloutier, Nathalie; Tan, Sisareuth; Boudreau, Luc H et al. (2013) The exposure of autoantigens by microparticles underlies the formation of potent inflammatory components: the microparticle-associated immune complexes. EMBO Mol Med 5:235-49
Magarinos, Natalia J; Bryant, Katherine J; Fosang, Amanda J et al. (2013) Mast cell-restricted, tetramer-forming tryptases induce aggrecanolysis in articular cartilage by activating matrix metalloproteinase-3 and -13 zymogens. J Immunol 191:1404-12
Fujimura, Ken; Sasaki, Atsuo T; Anderson, Paul (2012) Selenite targets eIF4E-binding protein-1 to inhibit translation initiation and induce the assembly of non-canonical stress granules. Nucleic Acids Res 40:8099-110
Oyoshi, Michiko K; He, Rui; Li, Yitang et al. (2012) Leukotriene B4-driven neutrophil recruitment to the skin is essential for allergic skin inflammation. Immunity 37:747-58
Adachi, Roberto; Krilis, Steven A; Nigrovic, Peter A et al. (2012) Ras guanine nucleotide-releasing protein-4 (RasGRP4) involvement in experimental arthritis and colitis. J Biol Chem 287:20047-55
Darce, Jaime; Rudra, Dipayan; Li, Li et al. (2012) An N-terminal mutation of the Foxp3 transcription factor alleviates arthritis but exacerbates diabetes. Immunity 36:731-41
Emara, Mohamed M; Fujimura, Ken; Sciaranghella, Daniele et al. (2012) Hydrogen peroxide induces stress granule formation independent of eIF2ýý phosphorylation. Biochem Biophys Res Commun 423:763-9
Simarro, Maria; Giannattasio, Giorgio; Xing, Wei et al. (2012) The translational repressor T-cell intracellular antigen-1 (TIA-1) is a key modulator of Th2 and Th17 responses driving pulmonary inflammation induced by exposure to house dust mite. Immunol Lett 146:8-14

Showing the most recent 10 out of 43 publications