Systemic sclerosis (SSc) is a rare, complex rheumatic disease involving multiple organ systems with a frequently fatal outcome. It remains one of the most difficult rheumatic disease to manage, with limited effective therapies. There are several impediments to more rapid advances in understanding SSc pathogenesis and finding new treatments. First, the relative rarity of SSc and need of these patients for specialty clinical care has concentrated translational studies in select institutions having an adequate patient base and a program for sample/tissue collection. Thus many investigators have little or no access to patient samples/tissues. Even for investigators seeing relatively large numbers of patients, large sample sizes for proving associations between clinical disease and pathogenic features under study can prove elusive. Second, the heterogeneity of patient presentation and disease progression leads to fragmented approaches to understanding pathogenesis, different investigators studying different disease manifestations, for example, skin fibrosis compared to pulmonary arterial hypertension. Third, advanced technologies, such as microarray and proteomics are applied using different platforms, rendering interpretation of studies across different sites difficult. Empowered by a Consortia of SSc investigators formed to address these problems, this Core Center will leverage existing institutional resources to form four cores, providing patient samples and common platforms for advanced technologies designed to serve the broad clinical, translational basic scientific interests of Consortia Investigators. The Administrative Core (Core A), will provide structure, communication and enrichment of Core Investigators. Two cores (Cores B and C) will array pathological specimens from skin and lung, respectively, from SSc patients for rapid immunohistochemical evaluation of target proteins. Two cores will provide Consortia Investigators access to powerful Proteomic (Core D) and Microarray (Core E) technologies. All Cores will additionally use economy-of-scale and Core funding to provide services at a fraction of normal cost. In addition, the common platform and clinical data collected across cores will provide a large, common database for understanding clinical-pathological associations.
SSc is a devastating rheumatic condition often leading to death. Because the disease is uncommon, it has been difficult to organize resources and obtain adequate sample numbers to understand disease pathogenesis. This Core Center will provide a mechanism for a consortia of investigators with strong records of accomplishment in SSc research to utilize common cores and platforms for high technology analyses.
|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|
Showing the most recent 10 out of 49 publications