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Rheumatology Research

Rheumatology

Our mission is to develop and support research programs leading to improved understanding, effective therapies, and prevention of the rheumatic and systemic autoimmune diseases.

History

Founded in 1863, HSS is a non-profit hospital dedicated to rheumatic and orthopaedic diseases. Since the inception of an academic program in rheumatology following the appointment of Richard Freyberg in 1945, HSS has shown a steady and growing research commitment. Dr. Charles Christian was instrumental in building a research base that was fully integrated with clinical activities in rheumatic diseases, providing a strong environment for successful research. Since 1996, Dr. Stephen Paget has continued the tradition of strong support for research activities that are characterized by detailed and focused investigation of the basic pathogenic mechanisms of human autoimmune and rheumatic diseases. In this unique environment, basic research is integrated with patient-oriented research through daily interactions and collaborations among rheumatologists and investigators active in clinical activities and bench research.

Over the past 10 years, HSS has held NIH/NIAMS Multipurpose Arthritis and Musculoskeletal Disease Center and Specialized Center of Research in Lupus grants, as well as individual research awards from NIH, the Arthritis Foundation, the S.L.E. Foundation, Inc., the Alliance for Lupus Research, the Lupus Research Institute, and other funding agencies. The Barbara Volcker Center for Women and Rheumatic Disease was established in 1997, and the Mary Kirkland Center for Lupus Research was established in 2001. Lupus and Rheumatoid Arthritis Patient Registries and Tissue/DNA Repositories established since 1995 now include clinical information, tissue, and DNA samples from more than 1500 patients.

Throughout its distinguished history, HSS Rheumatology Research has taken the approach that progress in understanding systemic lupus erythematosus, rheumatoid arthritis, and other rheumatic diseases will move most rapidly toward new and more effective therapies if basic research is combined with research driven by the patient. There are few centers of rheumatic disease research as well organized for multidisciplinary studies of underlying disease mechanisms and clinical aspects of rheumatic and systemic autoimmune diseases by collaborating basic and clinical scientists, of whom many are rheumatologists.

Milestones

1960's

  • Development of mouse models of lupus - Dr. Robert C. Mellors

1970's

  • Demonstration of T cells in rheumatoid synovium - Dr. Stephen A. Paget
  • Role of Type C retrovirus in murine lupus - Dr. Robert C. Mellors
  • Demonstration of impaired clearance of immune complexes in SLE - Dr. Robert P. Kimberly
  • Role of hepatitis B antigen in immune complexes of vasculitis - Dr. Charles L. Christian

1980's

  • High-dose intravenous methylprednisolone pulse therapy in systemic lupus erythematosus - Drs. Robert P. Kimberly, Michael D. Lockshin, and Charles L. Christian
  • Characterization of mechanisms of T cell-B cell interaction - Drs. Stephen M. Friedman and Mary K. Crow
  • Characterization of the role of Fc receptors in phagocytosis - Drs. Robert P. Kimberly and Jane E. Salmon
  • Association of anti-P autoantibodies with CNS lupus - Dr. Keith B. Elkon
  • Association of anti-phospholipid antibodies with fetal loss - Drs. Michael D. Lockshin, Azzudin Gharavi, and Lisa Sammaritano
  • The effect of pregnancy on lupus - Dr. Michael D. Lockshin

1990's

  • Identification of the first human lupus gene: FcgRII - Drs. Jane E. Salmon and Robert P. Kimberly
  • Discovery of the genetic basis of disease acceleration in MRL/lpr lupus mice - Dr. Keith B. Elkon
  • Identification of the molecular basis of lymphoproliferation in the Canale-Smith Syndrome - Dr. Keith B. Elkon
  • Identification of autoantigen-specific T cells in lupus - Dr. Mary K. Crow
  • Characterization of the effect of microbial superantigens on the humoral immune response - Drs. Stephen M. Friedman and Mary K. Crow
  • Definition of T cell receptor Vbeta expression on rheumatoid arthritis T cells - Drs. Mary K. Crow and Stephen M. Friedman
  • Description of altered CD40 ligand expression in SLE - Dr. Mary K. Crow
  • Description of impaired cytokine signaling through the Jak-STAT pathway in rheumatoid arthritis - Dr. Lionel B. Ivashkiv

2000's

  • Description of the role of complement in anti-phospholipid antibody-mediated fetal loss - Dr. Jane E. Salmon
  • Demonstration of an inhibitory Fc receptor on human monocytes - Dr. Luminita Pricop
  • Description of a CD28 pathway phosphatase - Dr. Philip King

Research Programs

Basic research activities are organized by programs.

The immune system, including the cells of the innate immune response, antigen-specific lymphocytes, and their antibody and cytokine products, is central to our capacity to coexist with potentially pathogenic microbes. Ironically, the same cells and mediators of the immune system are responsible for the inflammation and tissue damage that cause disease in systemic lupus erythematosus, rheumatoid arthritis, and the other autoimmune disorders that are treated by rheumatologists at HSS. HSS rheumatology investigators participate in an integrated program of research and education, with a strong focus on the cells and molecules that account for normal immune system function and the immunopathogenic mechanisms of human rheumatic and autoimmune diseases. It is this emphasis on the basic mechanisms that underlie human disease, in an environment with rich patient resources established to serve rheumatic disease research, that is a unique feature of basic rheumatology research at HSS.

Priority areas for basic rheumatology research at HSS include:

  • genetic basis of systemic autoimmune disease
  • immunoregulation in systemic autoimmune disease
  • effector mechanisms and target organ damage in systemic autoimmune disease

Clinical research areas include:

  • Cognitive Disorders in Autoimmune Disease
  • Gender and Autoimmune Disease
  • Hormone Effects on SLE
  • Outcomes in Rheumatic Diseases
  • Premature Atherosclerosis in SLE and RA

Research Faculty

See Research Professional Staff

Core Facilities

See Research Core Facilities

Patient Registries and Repositories

Among the most valuable resources available to HSS investigators are the SLE, RA, and Pediatric SLE Registries and Repositories. The SLE Registry is directed by Drs. Jane Salmon, the RA Registry is directed by Dr. Melanie Harrison, and the RA Sample Repository is directed by Dr. Lionel Ivashkiv. The Pediatric SLE Registry is supported by The S.L.E. Foundation, Inc. and the Toys-R-Us Foundation and is co-directed by Drs. Karen Onel and Tom Lehman. The Registries contain clinical data, demographic information, and biological specimens collected quarterly from patients that meet ACR criteria for the diseases. Detailed information regarding ethnicity, as well as disease activity, antibody status, and medications are recorded at the time of sample collection. For the SLE patients, blood is collected for both serum and DNA, and for the RA patients, synovial fluid and tissue are also stored when they become available in the course of clinical care. These resources are available to HSS investigators who hold IRB approval for studies that require the Registry and Repository materials, and investigators external to HSS are granted access to materials from the Registries after approval by a Registry Oversight Committee.

  • SLE Patient Registry and Repository
  • Rheumatoid Arthritis Patient Registry
  • Rheumatoid Arthritis DNA and Serum Repository
  • Pediatric SLE Registry and Repository
  • Clinical Outcome Registry

Training Programs

  • HSS Rheumatology Fellowship Training Programs
  • NIH Funded Program in Rheumatic Disease Research
  • Immunology Program, Weill Medical College Graduate School of Medical Sciences
  • Tri-Institutional MD-PhD Program