To date, most of the clinical trials in systemic sclerosis (SSc) have been negative trials. One of the reasons for this may be that enrolled subjects are clinically heterogeneous and only a small subset of SSc patients respond to any one therapy. Better methods of classifying patients into clinically relevant subsets are needed. Multi-Analyte Profiling? (MAP) is cutting edge ELISA-based technology that determines levels of serum biomarkers in an unbiased manner by simultaneously measuring hundreds of analytes using small serum sample volumes. Preliminary studies using MAP suggest that there are differences In levels of serum proteins among SSc patients with or without pulmonary arterial hypertension;however, studies have been limited by sample sizes consisting of patients enrolled at a single center. The establishment of a Proteomics and Clinical Core as part of the larger PSO grant will fund the establishment of a linked SSc serum repository and clinical database. Applying MAP technology to hundreds of serum samples will permit identification of a smaller subset of proteins that reliably predicts disease phenotype in a cost-effective manner. This serum protein signature will be validated and will then be used In subsequent clinical trials to ensure that patients with similar disease phenotype are enrolled. The Proteomics and Clinical Core will address three specific aims namely 1) to establish a state-of-the-art electronic SSc patient registry and biorepository that contains serum samples from SSc patients and appropriate controls along with relevant clinical information that is collected using standardized approaches, 2) apply Multi-Analyte Profile? technology to 264 SSc and healthy control serum samples to discover and validate a small, core set of important SSc protein biomarkers. 3) work closely with the Bioinformatics Core to discover important associations between serum protein levels and clinical markers of SSc disease activity.
Systemic sclerosis (SSc) is a clinically diverse disease. Preliminary studies testing new biomarkers, such as testing blood protein levels, suggest that levels differ amongst clinically distinct SSc patients. We propose to test blood samples from hundreds of patients for blood proteins to Identify a small set of blood markers that reliably predict distinct clinical subsets of patients.
|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|
|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|
|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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