Microarray analysis of clinical samples has provided useful insight into the biological processes and diversity of cell types in complex diseases that includes systemic autoimmune disease. Analysis of tissues such as skin, tumors and peripheral blood cells allows the quantitative characterization of the diversity in sample phenotypes as well as the biological pathways that are deregulated in the disease. The analysis of tumors has demonstrated its ability to quantitatively and reproducibly separate tumors into subtypes with different prognoses, to identify pathways deregulated in the disease and to reveal infiltrating cells. Application of microarray technology to scleroderma skin biopsies, isolated scleroderma cell lines and peripheral blood samples has shown that it will be an important tool for understanding the diversity in rheumatic diseases, as well as changes to the underlying gene expression pathways. In this core, we will use proven methods that have been developed and already successfully implemented in the core Pi's laboratory to analyze skin biopsy samples and peripheral blood mononuclear cells taken from patients with systemic sclerosis and normal controls. High quality RNA will be prepared, hybridized to Agilent technologies whole-genome DNA microarrays by established protocols. Using these established methods, the core Pi's lab has hybridized more than 1000 Agilent microarrays over the past three years. All microarrays are normalized using standard methods and analyzed using a combination of algorithms that include testing for differential expression and pathway analysis. The goals of this core are:
Aim 1. Generate quality controlled DNA microarray hybridizations for each sample and process the resulting data using a standard analysis pipeline. Each sample will be hybridized to Agilent 44,000 element DNA microarrays, scanned on an Axon Instruments GenePix Scanner and submitted to a research microarray database.
Aim 2. Analysis of the resulting data for differentially expressed genes, gene expression signatures predictive of clinical endpoints and deregulated pathways.

Public Health Relevance

High-throughput gene expression analysis has allowed the definition of subsets of scleroderma and identified deregulated pathways that can be targeted therapeutically. A core that includes data analysis will allow the larger community to access this technology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Center Core Grants (P30)
Project #
5P30AR061271-02
Application #
8381782
Study Section
Special Emphasis Panel (ZAR1-MLB)
Project Start
Project End
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$151,168
Indirect Cost
Name
Boston University
Department
Type
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Ryu, Changwan; Sun, Huanxing; Gulati, Mridu et al. (2017) Extracellular Mitochondrial DNA Is Generated by Fibroblasts and Predicts Death in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med 196:1571-1581
Grzegorzewska, Agnieszka P; Seta, Francesca; Han, Rong et al. (2017) Dimethyl Fumarate ameliorates pulmonary arterial hypertension and lung fibrosis by targeting multiple pathways. Sci Rep 7:41605
Looney, Agnieszka P; Han, Rong; Stawski, Lukasz et al. (2017) Synergistic Role of Endothelial ERG and FLI1 in Mediating Pulmonary Vascular Homeostasis. Am J Respir Cell Mol Biol 57:121-131
Steinberg, Shannon M; Shabaneh, Tamer B; Zhang, Peisheng et al. (2017) Myeloid Cells That Impair Immunotherapy Are Restored in Melanomas with Acquired Resistance to BRAF Inhibitors. Cancer Res 77:1599-1610
Taroni, Jaclyn N; Greene, Casey S; Martyanov, Viktor et al. (2017) A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis. Genome Med 9:27
Artlett, Carol M; Sassi-Gaha, Sihem; Hope, Jennifer L et al. (2017) Mir-155 is overexpressed in systemic sclerosis fibroblasts and is required for NLRP3 inflammasome-mediated collagen synthesis during fibrosis. Arthritis Res Ther 19:144
Urso, Katia; Alvarez, David; Cremasco, Viviana et al. (2016) IL4RA on lymphatic endothelial cells promotes T cell egress during sclerodermatous graft versus host disease. JCI Insight 1:
Sargent, Jennifer L; Li, Zhenghui; Aliprantis, Antonios O et al. (2016) Identification of Optimal Mouse Models of Systemic Sclerosis by Interspecies Comparative Genomics. Arthritis Rheumatol 68:2003-15
Martyanov, Viktor; Whitfield, Michael L (2016) Molecular stratification and precision medicine in systemic sclerosis from genomic and proteomic data. Curr Opin Rheumatol 28:83-8
Ahluwalia, Neil; Grasberger, Paula E; Mugo, Brian M et al. (2016) Fibrogenic Lung Injury Induces Non-Cell-Autonomous Fibroblast Invasion. Am J Respir Cell Mol Biol 54:831-42

Showing the most recent 10 out of 42 publications