John M. Davis III, M.D., studies the impact of persistent viral infections, such as human cytomegalovirus (CMV), on chronic inflammatory diseases in humans. The long-term goal of Dr. Davis' research is to develop new therapies for the prevention and treatment of rheumatoid arthritis and other inflammatory rheumatic diseases.
Using the newest methods in translational human immunology, Dr. Davis and his team conduct patient-oriented studies to investigate the role of CMV and CMV-specific T-cell immunity in perpetuating inflammation in patients with rheumatoid arthritis.
His studies involve cytokine secretion assays, enzyme-linked immunospot (ELISPOT) assays, multiparameter flow cytometry, and multiplexed cytokine analysis for the enumeration and phenotypic assessment of CMV-specific effector-memory T cells.
Immunodominant peptides of CMV are used to assess antigen-specific function. Analyses associate CMV T cell behavior and function with clinical features, disease severity and treatment response.
Dr. Davis' research has been funded by the Mayo Clinic Center for Translational Science Activities, the Arthritis Foundation, Mayo Clinic, and Mr. Lawrence and Mrs. Ruth Eaton.
- Why do CMV-specific T cells traffic into the joints in patients with rheumatoid arthritis? Studies are under way to understand if it is CMV reactivation in the joints that mediates chemotaxis to the synovium — or if this is mediated by chemokine gradients.
- How do CMV-specific effector-type T cells provoke inflammation? Experiments are being conducted to define how CMV T cells become activated in the joints and how cytokine production or cytolytic activities mediate joint inflammation.
- What are the long-term effects of CMV-specific T cells on disease progression? Epidemiological studies are planned to determine the impact of CMV-specific T cell frequency and/or function on progression of radiographic joint damage and cardiovascular outcomes.
- How does HLA-DRB1 impact CMV-specific T cells? HLA-DRB1 is the major risk gene for rheumatoid arthritis. Studies are under way to evaluate the effects of HLA-DRB1 shared epitope genes on the diversity of CMV-specific T cells in patients with rheumatoid arthritis and controls with latent CMV infection. These investigations could define a new mechanism for this gene in determining the occurrence and outcome of rheumatoid arthritis.
Significance to patient care
Dr. Davis' research into the impact of CMV persistence on the immune system and on the occurrence and progression of chronic inflammatory diseases — such as rheumatoid arthritis — will lead to new insights regarding pathogenesis and novel targeted therapies that improve health and survival for affected people.
- Research Chair, Division of Rheumatology, Mayo Clinic, 2011-present
- Award for Outstanding Arthritis Research, Arthritis Foundation North Central Chapter, 2005