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.
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
- 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.
We also have a separate clinical trials unit with 4-8 active trials in the areas of rheumatoid arthritis, spondyloarthritis and osteoarthritis. This unit is directed by Dr. Jonathan Kay with staff support from Steven Ball and Janice Weaver.