The objective of the RA and SLE AMP is to design and conduct cutting-edge molecular de-construction of the cellular, genetic, and immunologic pathways of RA and SLE. The goal of the Leadership Center (LC) is to establish a collaborative network comprised of the LC and multiple Research Sites (RS), operating a program that is both scientifically and financially efficient. LCMP Components A and B (Project and Operational Management) will establish procedures for monitoring, reporting and assessing the progress of the RS and LC. In collaboration with the NLC, it will establish and implement SOPs. It will establish an integrated, AMP Network-wide project management infrastructure, and information technology for tracking and reporting all of the key activities of the AMP Network. LCMP Component C, Data Coordination and Management (DCM) will define and manage shared computational and data acquisition and create data capture protocols and interface with clinical phenotype, tissue sample and molecular assay domains, and provide training to AMP staff. LCMP Component D, Statistical Research (SR) will devise, assess and optimize quality control pipelines for phase 0 and P&F studies, conduct analyses of phase 1 data in order to recommend study designs for phase 2. It will define standards for analyses and ensure broad use of AMP data by internal an external researchers. Systems Biology and Bioinformatics (SysBio) will devise focused algorithms to analyze individual molecular data types and integrative algorithms to analyze multiple types of data in aggregate. It will generate falsifiable hypotheses linking molecular data to clinical phenotypes and assess the credibility of proposed hypotheses. The Tissue Acquisition and Research Group (TRG) will develop standardized methods for sample collection, processing and storage, QA samples and provide a computerized and centralized sample tracking system. Together, these components of the LC will provide the support and infrastructure for operation of the AMP Network toward its goals of identifying biomarkers and targets for treating RA and SLE.

Public Health Relevance

Rheumatoid Arthritis and Systemic Lupus Erythematosus are inflammatory diseases that affect the skin, joints and kidneys. White blood cells and antibodies accumulate and damage these tissues causing pain and organ failure. We have outlined a plan to identify the molecules that regulate the inflammation that cause these diseases in order to define the best targets for the next generation of drugs to treat these diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Cooperative Agreement Phase I (UH2)
Project #
1UH2AR067677-01
Application #
8852273
Study Section
Special Emphasis Panel (ZAR1-CNR (M1))
Program Officer
Serrate-Sztein, Susana
Project Start
2014-09-24
Project End
2016-05-31
Budget Start
2014-09-24
Budget End
2015-05-31
Support Year
1
Fiscal Year
2014
Total Cost
$452,001
Indirect Cost
$81,289
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Hinks, Anne; Marion, Miranda C; Cobb, Joanna et al. (2018) Brief Report: The Genetic Profile of Rheumatoid Factor-Positive Polyarticular Juvenile Idiopathic Arthritis Resembles That of Adult Rheumatoid Arthritis. Arthritis Rheumatol 70:957-962
Davenport, Emma E; Amariuta, Tiffany; Gutierrez-Arcelus, Maria et al. (2018) Discovering in vivo cytokine-eQTL interactions from a lupus clinical trial. Genome Biol 19:168
Slowikowski, Kamil; Wei, Kevin; Brenner, Michael B et al. (2018) Functional genomics of stromal cells in chronic inflammatory diseases. Curr Opin Rheumatol 30:65-71
Nigrovic, Peter A; Raychaudhuri, Soumya; Thompson, Susan D (2018) Review: Genetics and the Classification of Arthritis in Adults and Children. Arthritis Rheumatol 70:7-17
Westra, Harm-Jan; Martínez-Bonet, Marta; Onengut-Gumuscu, Suna et al. (2018) Fine-mapping and functional studies highlight potential causal variants for rheumatoid arthritis and type 1 diabetes. Nat Genet 50:1366-1374
Finucane, Hilary K; Reshef, Yakir A; Anttila, Verneri et al. (2018) Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types. Nat Genet 50:621-629
Fonseka, Chamith Y; Rao, Deepak A; Raychaudhuri, Soumya (2017) Leveraging blood and tissue CD4+ T cell heterogeneity at the single cell level to identify mechanisms of disease in rheumatoid arthritis. Curr Opin Immunol 49:27-36
Hinks, A; Bowes, J; Cobb, J et al. (2017) Fine-mapping the MHC locus in juvenile idiopathic arthritis (JIA) reveals genetic heterogeneity corresponding to distinct adult inflammatory arthritic diseases. Ann Rheum Dis 76:765-772
Der, Evan; Ranabothu, Saritha; Suryawanshi, Hemant et al. (2017) Single cell RNA sequencing to dissect the molecular heterogeneity in lupus nephritis. JCI Insight 2:
Frisell, Thomas; Hellgren, Karin; Alfredsson, Lars et al. (2016) Familial aggregation of arthritis-related diseases in seropositive and seronegative rheumatoid arthritis: a register-based case-control study in Sweden. Ann Rheum Dis 75:183-9

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