William F.C. Rigby, M.D.
Professor of Medicine
Professor of Microbiology and Immunology
Microbiology and Immunology
Harvard Medical School, MD 1979
Columbia University, BA 1974
After postdoctoral work in Dr. Michael Fanger's laboratory in the Department of Microbiology at Dartmouth Medical School, Dr. Rigby completed subspecialty training in rheumatology and joined the faculty at Dartmouth Medical School in 1987.
Neuroscience Center at Dartmouth
Program in Experimental and Molecular Medicine
Dartmouth Hitchcock Medical Center
Borwell Research Bldg. - HB 7510
1 Medical Center Drive
Lebanon NH 03756
Dr. Rigby's laboratory integrates his basic scientific and clinical interests. On a translational level, Dr. Rigby is examining the changes that accompany clinical responses in patients with rheumatoid arthritis treated with biologics. His basic scientific efforts examine the mechanism by which CD40 ligand (CD154) and cytokine expression are regulated at post-transcriptional levels. Many cytokines are encoded by mRNA that contain reiterated AUUUA sequences in their 3' UTR. These AU-rich sequences (AURE) have been shown to modulate the translation as well as rapid degradation of these mRNA. His laboratory has been active in identifying proteins that bind to AURE and regulate these events. Of late, he has studied the regulation of CD154 (CD40 ligand), a member of the TNF gene family that plays a critical role in the immune response. In contrast to cytokine genes, CD154 is regulated by its rate of cytoplasmic mRNA turnover and translation. The CD154 3'UTR mRNA contains two separate cis-acting elements, the cytidine-uridine (CU)- and cytidine-adenine (CA)-rich elements that respectively regulate these two activities. Interestingly the CA rich element is polymorphic in the human; certain polymorphisms have been associated with the development of rheumatoid arthritis and systemic lupus erythematosus.
These findings have prompted Dr. Rigby to begin translational studies of patients with rheumatologic disease to determine if: a) CD154 dysregulation is present; b) Is this dysregulation influenced by disease activity; c) Does this dysregulation correlate with CA-repeat polymorphisms? In this manner, Dr. Rigby will begin to address epigenetic and genetic factors that regulate the expression of this critical immunoregulatory molecule.
Efficacy and safety of tabalumab, an anti-B-cell-activating factor monoclonal antibody, in patients with rheumatoid arthritis who had an inadequate response to methotrexate therapy: results from a phase III multicentre, randomised, double-blind study.
Reply: To PMID 24719284.
Induction of interleukin-6 production by rituximab in human B cells.
Pancytopenia and cough in a man with amyopathic dermatomyositis.
Depletion of hnRNP A2/B1 overrides the nuclear retention of the HIV-1 genomic RNA.
Safety of rituximab in combination with other biologic disease-modifying antirheumatic drugs in rheumatoid arthritis: an open-label study.
Rituximab mediates loss of CD19 on B cells in the absence of cell death.
Unusual case of a swollen painful toe in a young man.
Increased frequency of complement C4B deficiency in rheumatoid arthritis.
Effect of rituximab on physical function and quality of life in patients with rheumatoid arthritis previously untreated with methotrexate.