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)
Project #
Application #
Study Section
Special Emphasis Panel (ZAR1-MLB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Boston University
United States
Zip Code
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

Showing the most recent 10 out of 33 publications