Systemic sclerosis (SSc;scleroderma) is an idiopathic disorder of connective tissue characterized by increased production and deposition of collagen in the skin and internal organs such as the lungs and kidneys. The etiology of SSc is unknown, necessitating ongoing investigation into its cause and possible cure. Since the use of ACE inhibitors for the treatment of renal involvement, interstitial lung disease (ILD) has become the most common cause of death in SSc. The pulmonary complications of SSc are often underrecognized until their later stages. Fifty to 80% of all SSc patients have pulmonary disease, most commonly ILD and pulmonary arterial hypertension (PAH). This further emphasizes the critical importance of defining markers for risk of developing PAH and ILD, identifying better screening tools, and facilitating earlier detection. Currently, no therapies are available which have been shown in placebo-controlled studies to halt the progression of PF or PAH in SSc or reverse it, and lung transplantation remains the only option. Through the Lung Pathology Core, we propose to generate lung tissue microarrays that will provide a unique and valuable resource for the SSc Core Investigators and the Scleroderma research community to conduct high throughput screening of proteins and mRNA in disease and control tissues using sections generated simultaneously from multiple patient samples. We will also provide comprehensive clinical information on patients from whom lung tissues are obtained thus facilitating correlation studies of tissue microarray analysis and disease clinical variables. This will facilitate studies exploring the pathogenesis of lung disease as well as propel research in the field, which has been hampered by the unavailability of patient lung samples. We also propose to utilize a similar approach and provide a service for investigators conducting animal research who wish to examine samples from multiple animal model treatment time points or different models simultaneously. Our approach will thus generate valuable resources and a unique service for Core users and Scleroderma research, and will thus contribute to a better understanding of key molecules involved the pathogenesis of SSc-associated lung disease.

Public Health Relevance

Lung disease in SSc is a devastating complication often leading to death. Accesss to pathological samples is limited but these samples can be obtained at the time of lung transplant. This Core will provide arrayed samples of lung tissues from patients undergoing lung transplant, enabling investigators to quickly evaluate the role of different proteins under study in the pathogenesis of pulmonary disease in SSc.

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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Franks, Jennifer M; Cai, Guoshuai; Whitfield, Michael L (2018) Feature specific quantile normalization enables cross-platform classification of molecular subtypes using gene expression data. Bioinformatics 34:1868-1874
Oh, Raymond S; Haak, Andrew J; Smith, Karry M J et al. (2018) RNAi screening identifies a mechanosensitive ROCK-JAK2-STAT3 network central to myofibroblast activation. J Cell Sci 131:
Fleury, Michelle; Belkina, Anna C; Proctor, Elizabeth A et al. (2018) Increased Expression and Modulated Regulatory Activity of Coinhibitory Receptors PD-1, TIGIT, and TIM-3 in Lymphocytes From Patients With Systemic Sclerosis. Arthritis Rheumatol 70:566-577
Rice, Lisa M; Mantero, Julio C; Stratton, Eric A et al. (2018) Serum biomarker for diagnostic evaluation of pulmonary arterial hypertension in systemic sclerosis. Arthritis Res Ther 20:185
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
Rice, Lisa M; Mantero, Julio C; Stifano, Giuseppina et al. (2017) A Proteome-Derived Longitudinal Pharmacodynamic Biomarker for Diffuse Systemic Sclerosis Skin. J Invest Dermatol 137:62-70
Lafyatis, Robert; Mantero, Julio C; Gordon, Jessica et al. (2017) Inhibition of ?-Catenin Signaling in the Skin Rescues Cutaneous Adipogenesis in Systemic Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial of C-82. J Invest Dermatol 137:2473-2483
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
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

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