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.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Center Core Grants (P30)
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Special Emphasis Panel (ZAR1-MLB)
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Boston University
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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:
Ziemek, Jessica; Man, Ada; Hinchcliff, Monique et al. (2016) The relationship between skin symptoms and the scleroderma modification of the health assessment questionnaire, the modified Rodnan skin score, and skin pathology in patients with systemic sclerosis. Rheumatology (Oxford) 55:911-7
Nazari, Banafsheh; Rice, Lisa M; Stifano, Giuseppina et al. (2016) Altered Dermal Fibroblasts in Systemic Sclerosis Display Podoplanin and CD90. Am J Pathol 186:2650-64
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
Mendoza, Fabian A; Piera-Velazquez, Sonsoles; Farber, John L et al. (2016) Endothelial Cells Expressing Endothelial and Mesenchymal Cell Gene Products in Lung Tissue From Patients With Systemic Sclerosis-Associated Interstitial Lung Disease. Arthritis Rheumatol 68:210-7
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
Christmann, Romy B; Wooten, Alicia; Sampaio-Barros, Percival et al. (2016) miR-155 in the progression of lung fibrosis in systemic sclerosis. Arthritis Res Ther 18:155
Ramos, Paula S; Silver, Richard M; Feghali-Bostwick, Carol A (2015) Genetics of systemic sclerosis: recent advances. Curr Opin Rheumatol 27:521-9
Rice, Lisa M; Padilla, Cristina M; McLaughlin, Sarah R et al. (2015) Fresolimumab treatment decreases biomarkers and improves clinical symptoms in systemic sclerosis patients. J Clin Invest 125:2795-807
Roach, Katy M; Feghali-Bostwick, Carol A; Amrani, Yassine et al. (2015) Lipoxin A4 Attenuates Constitutive and TGF-β1-Dependent Profibrotic Activity in Human Lung Myofibroblasts. J Immunol 195:2852-60

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