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.
|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|
|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|
|Steinberg, Shannon M; Shabaneh, Tamer B; Zhang, Peisheng et al. (2017) Myeloid Cells That Impair Immunotherapy Are Restored in Melanomas with Acquired Resistance to BRAF Inhibitors. Cancer Res 77:1599-1610|
|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|
|Artlett, Carol M; Sassi-Gaha, Sihem; Hope, Jennifer L et al. (2017) Mir-155 is overexpressed in systemic sclerosis fibroblasts and is required for NLRP3 inflammasome-mediated collagen synthesis during fibrosis. Arthritis Res Ther 19:144|
|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:|
|Sargent, Jennifer L; Li, Zhenghui; Aliprantis, Antonios O et al. (2016) Identification of Optimal Mouse Models of Systemic Sclerosis by Interspecies Comparative Genomics. Arthritis Rheumatol 68:2003-15|
|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|
|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|
Showing the most recent 10 out of 42 publications