The Rheumatic Diseases Research Core center and now the Rheumatic Diseases Resource-based Core Center (RDRCC) has been funded by the National Institutes of Health and the National Institute of Arthritis, Musculoskeletal and Skin Diseases grants P30-AR053503 since 2006 and continuing as P30-AR070254 since 2015. RDRCC focuses on providing the framework for organizational (oversight, management), operational (recruitment, sampling, processing), measurement and analytical (statistical, computational, and integrative) expertise to enable effective clinical and translational research. The Center is designed to foster collaborative and synergistic discovery by maximizing access of the diverse research community to data and samples from humans with rheumatic diseases.
The long-term objective for the Center is maximize scholarship about the causes and mechanisms of rheumatic diseases that will improve treatment and outcomes and help to prevent the development of autoimmune rheumatic diseases.
The Aims of the RDRCC are to:
- Provide access to rigorously collected data and biological samples from large, prospective, well-characterized cohorts of patients with rheumatic diseases;
- Enable innovative research through directly providing, or easing access to, relevant Core services, and providing the means to validate new discoveries; and
- Increase methodologic and disease-specific literacy thus promoting interdisciplinary collaborations through an active enrichment program.
RDRCC has undergone remarkable growth and greatly enhanced productivity in rheumatic disease research at Johns Hopkins by coupling the extraordinarily rich sources of clinical information and biological material from the Centers of Excellence to the investigative enterprise. We further leverage philanthropic funds to greatly increase the number of pilot projects that use these RDRCC Core resources. The RDRCC and pilot funds have been particularly helpful to junior investigators, enabling them to submit successful independent grant proposals using the preliminary data that they generated. The RDRCC also provides investigators at distant sites access to the valuable patient samples collected in the Centers of Excellence and to the novel bioassays available through our laboratories. Lastly, the sample collection, core expertise and assays that the P30 made available allowed us to recruit additional outstanding investigators to ask questions about rheumatic diseases for which they previously lacked access, expertise, or resources to pursue.
The RDRCC continues to build on its significant momentum established in past funding periods, by maintaining our research focus on humans with rheumatic diseases, and leveraging prior success in organization, structure and management. Over time, we continue to modify and sculpt the Center to allow mature components to become independent, and to add expertise and function in areas identified as critical for additional growth and success.
The primary objective of the RDRCC is to maximize scholarship about the causes, mechanisms, treatment, and prevention of autoimmune rheumatic diseases through:
- providing access to rigorously collected data and biological samples from large populations of highly phenotyped patients with rheumatic diseases
- effectively enabling novel research through directly providing, or easing access to, relevant Core services and providing the means to validate new discoveries
- increasing literacy and initiating new collaborations through an active enrichment program
The RDRCC includes an Administrative Core (Core A), and 3 scientific Cores (Cores B-D).
The Administrative Core integrates all scientific and enrichment activities of the Cores, maintains communication between the Cores and with the research base, and provides budgetary management and oversight, all within the context of the overall Divisional and institutional clinical/ translational research framework. This Core also administers enrichment programs and the Core Coins program providing additional resources to investigators.
Core B (Research Management and Patient Integrated Data, RAPID) enhances access to patient populations for investigators interested in rheumatic diseases by: a) Streamlining the process of human subjects research study initiation, operationalization, and oversight; b) Facilitating the integration of high quality clinical and research data, and c) Supporting and fostering patient centered outcomes research.
Core C (Sample Processing and Immunoassay Research, SPIRE) provides infrastructure to manage biospecimens from rheumatic diseases, high quality assays to facilitate discovery and pathway validation, and serves as a conduit for researchers to broader institutional expertise and resources.
Core D, (Data Science Core) embeds biomedical data scientists within each COE to determine specific analytical needs and to apply modern statistical and computing methods in the longitudinal cohorts and integrated laboratory data to identify disease and outcome trajectories, and translate these results into improved prognostic and treatment response indicators.
Dr. Antony Rosen, the Mary Betty Stevens Professor of Medicine, serves as the Director of the RDRCC. He has a long history of basic and translational research expertise, directing a major laboratory that has made seminal discoveries in apoptosis and autoantigen generation, and autoantibody development and propagation. Dr. Bingham is Professor of Medicine and Director of the Johns Hopkins Arthritis Center and serves as the Co-Director of the RDRCC. He is a skilled clinical investigator in the Rheumatic diseases, with expertise in clinical trials of investigational therapeutics, outcome measure development, translational research on disease initiation and propagation in rheumatoid arthritis and osteoarthritis, and in patient-centered outcomes research. Although Dr. Rosen and Dr. Bingham have largely distinct research skills, they represent the important perspectives of all constituencies of the research base and across the research continuum.
Discoveries Made Possible by RDRCC
The Core Center has generated exciting new knowledge. In the prior funding period, examples include novel autoantibodies that define new disease subgroups: (i) autoantibodies to PAD4 in RA, including PAD-activating autoantibodies, and their association with lung disease; (ii) autoantibodies to HMG coA-reductase in a novel immune-mediated necrotizing myopathy; (iii) antibodies to RNA polymerase III in scleroderma associating with increased cancer risk; and (iv) new description of the phenotype associated with antibodies to MDA5. Additional studies enabled by RDRCC have shown similarities between fibrosis pathways and immune responses in stiff skin syndrome and scleroderma, markers of specific IFN signals in different autoimmune rheumatic diseases; associations between cancer and myositis immune responses; and identification of new serum markers of Lyme disease activity. Clinical studies facilitated by RDRCC include patient centered outcomes research studies in RA; studies on cardiac function and coronary artery calcification in RA; and an evaluation of peripheral quantitative CT (pQCT) for arthritis imaging. Using advanced analytical capabilities through RDRCC studies have been conducted applying Bayesian Hierarchical Models in Scleroderma; and novel big data approaches to explore biomarker-phenotype associations.