Extensive genome sequencing efforts and advances in microarray technology have converged to create revolutionary new opportunities for high-throughput analyses of gene expression. Within the context of the Program, gene expression analyses will provide information critical to elucidating the mechanisms by which huntingtin and DNA-binding therapeutic agents alter gene expression. The Gene Expression Profiling Core will support the Program's individual Projects by tracking the expression of thousands of mRNAs simultaneously in the respective experimental systems, thereby identifying the specific gene targets of a given pathological or pharmacologic manipulation. Identifying the gene promoters subject to a particular effect will allow the promoter elements and transcription factor(s) responsible for the change to be elucidated. The Gene Expression Core will provide expertise in the design, execution and analysis of microarray profiling studies and will carry out confirmatory analyses using independent methodologies, such as northern blotting. The Principal Investigator of the Core has extensive experience in microarray based expression analyses, including several previous studies of mouse models of polyglutamine disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS045242-02
Application #
7553889
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
2
Fiscal Year
2004
Total Cost
$208,044
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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McFarland, Karen N; Das, Sudeshna; Sun, Ting Ting et al. (2013) Genome-wide increase in histone H2A ubiquitylation in a mouse model of Huntington's disease. J Huntingtons Dis 2:263-77
Taylor, David M; Moser, Roger; Regulier, Etienne et al. (2013) MAP kinase phosphatase 1 (MKP-1/DUSP1) is neuroprotective in Huntington's disease via additive effects of JNK and p38 inhibition. J Neurosci 33:2313-25
McFarland, Karen N; Das, Sudeshna; Sun, Ting Ting et al. (2012) Genome-wide histone acetylation is altered in a transgenic mouse model of Huntington's disease. PLoS One 7:e41423
Sleiman, Sama F; Langley, Brett C; Basso, Manuela et al. (2011) Mithramycin is a gene-selective Sp1 inhibitor that identifies a biological intersection between cancer and neurodegeneration. J Neurosci 31:6858-70
Hu, Yi; Chopra, Vanita; Chopra, Raman et al. (2011) Transcriptional modulator H2A histone family, member Y (H2AFY) marks Huntington disease activity in man and mouse. Proc Natl Acad Sci U S A 108:17141-6
Ebbel, Erika N; Leymarie, Nancy; Schiavo, Susan et al. (2010) Identification of phenylbutyrate-generated metabolites in Huntington disease patients using parallel liquid chromatography/electrochemical array/mass spectrometry and off-line tandem mass spectrometry. Anal Biochem 399:152-61
Zucker, Birgit; Kama, Jibrin A; Kuhn, Alexandre et al. (2010) Decreased Lin7b expression in layer 5 pyramidal neurons may contribute to impaired corticostriatal connectivity in huntington disease. J Neuropathol Exp Neurol 69:880-95
Benn, Caroline L; Luthi-Carter, Ruth; Kuhn, Alexandre et al. (2010) Environmental enrichment reduces neuronal intranuclear inclusion load but has no effect on messenger RNA expression in a mouse model of Huntington disease. J Neuropathol Exp Neurol 69:817-27
Kim, Jinho; Amante, Daniel J; Moody, Jennifer P et al. (2010) Reduced creatine kinase as a central and peripheral biomarker in Huntington's disease. Biochim Biophys Acta 1802:673-81

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