Department of Medicine

Research in the Division of Rheumatology spans the continuum from basic science investigation through to clinical and translational research and clinical trials. Research focuses on inflammatory arthritis and its effects on bone, as well as basic mechanisms of autoimmunity.

Basic Investigation

The research program in the Division of Rheumatology is focused on the innate and adaptive immune mechanisms that contribute to the onset, progression, persistence and regulation of systemic autoimmune diseases. The last decade has seen a paradigm shift in our understanding of the mechanisms underlying autoimmune and inflammatory diseases. We have come to realize that cross-regulation of immune system components and stromal elements plays a critical role in determining disease outcome and that aberrant regulation of innate immune system components has a major impact on the etiology of many immune and autoimmune diseases.

Studies from the division have contributed significantly to the new field of osteoimmunology, and have identified cytokines and pathways that regulate both inflammation and bone biology. We were the first to define the critical role of osteoclasts in bone destruction in RA and other forms of inflammatory arthritis. We were also among the first to demonstrate that detection of endogenous nucleic acids by endosomal members of the Toll-like receptor family can lead to the activation of autoreactive B cells and interferon-producing dendritic cells in the context of SLE and related disorders.  

Active areas of investigation now include the role of miRNAs derived from synovial tissues in the regulation of osteoblast differentiation, the impact of the Wnt signaling cascade on osteoblast function, the paradoxical role of the endosomal DNA sensor TLR9 and the cytosolic DNA sensor STING in the suppression of SLE-associated pathology and renal disease, and the connection between inappropriate clearance of DNA-associated debris, extramedullary hematopoiesis, and bone formation. These studies are greatly benefited by close collaborations between the Rheumatology faculty and members of the top-notch UMMS Program in Innate Immunity, who provide both exceptional expertise and experimental resources for many of the ongoing projects, as well as an outstanding intellectual environment of data clubs, informal discussions, and world-renowned seminar speakers. The division also has a commitment to translating the insights gleaned from animal models to the treatment of human disease and is working with local pharmaceutical companies to develop reagents for the diagnosis, and treatment of systemic autoimmune and arthritic disorders.  
See Dr. Gravallese's Laboratory
See Dr. Rothstein's Laboratory

Research Programs:

  • Transcriptional and miRNA regulation of bone formation and resorption
  • Nucleic acid sensing cytosolic sensor regulation of osteoblast activation
  • Mechanisms of bone formation in spondyloarthropathies
  • TLR9-dependent regulation of autoreactive B cells and granulocytes
  • Negative regulators of TLR activation in SLE
  • CD8 T cell driven pulmonary fibrosis
  • Proinflammatory activity of Fas-ligand in systemic and ocular pathology

Translational and Clinical Investigation

Drs. Gravallese, Kay and Upchurch oversee clinical and translational research in the Rheumatology division. Diseases we investigate include rheumatoid arthritis (RA), spondyloarthritis (including ankylosing spondylitis) and systemic lupus erythematosus (SLE). We are developing patient cohorts in RA and spondyloarthritis that will be instrumental in helping to understand disease mechanism and develop new therapies to prevent damage to the joints and spine.

Rheumatology Clinical Research Unit

The Rheumatology Clinical Research Unit (RCRU) of the Division of Rheumatology has extensive experience in conducting clinical research trials. The RCRU studies diseases that involve arthritis. Arthritis literally means inflammation of a joint.

To learn more about these conditions please click on the links listed below:

The RCRU specializes in clinical trials treatment options for osteoarthritis, rheumatoid arthritis, spondyloarthropathies (such as ankylosing spondylitis), and gout. The RCRU conducts a number of regional, national, and international studies that are both industry-sponsored and investigator-initiated.

Clinical trials are strictly controlled human studies of new and emerging therapies. At UMass Memorial Medical Center, these trials incorporate state-of-the-art patient care, while carefully evaluating how best to apply the most recent innovations in rheumatology.

The safety of study participants is our top priority. Clinical trials at UMass Memorial Medical Center must first be approved by an Institutional Review Board (IRB), which includes doctors, administrators, ethicists, and members of the general public. The IRB provides continuing surveillance of the trial as well as periodic review of study results. Before a treatment can be tested in people, it must be shown to be safe and effective in laboratory and animal studies. Volunteers are fully informed of possible risks and sign a consent form before being accepted into a clinical trial.

The safety and effectiveness of clinical trials are reviewed by the U.S. Food and Drug Administration. That agency determines if and when a clinical trial provides evidence that the treatment under study offers improvements in care that can be made available to all patients with a particular condition.

Before enrolling in a clinical trial, you will undergo the informed consent process. At this time, the investigator will explain the purpose of the trial, its expected benefits, any possible risks or side effects, and what your role will be. This is the time to ask questions. If you want to join the trial, you must sign the informed consent documents. You can leave a clinical trial at any time without penalty.

The director of the RCRU is Jonathan Kay, MD, an authority and researcher in rheumatoid arthritis and other forms of inflammatory arthritis. Other investigators include Ellen M Gravallese, MD, Chief of the Division of Rheumatology; Karen Salomon-Escoto, MD; and Katherine Upchurch, MD.  The RCRU staff consists of Steven Ball, RN, Clinical Research Coordinator.

To learn more about studies involving treatments for osteoarthritis, rheumatoid arthritis, and other treatment studies please telephone (508) 334-0221.