William F.C. Rigby, MD
Emeritus Professor of Medicine
Emeritus 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.
The thematic role of extracellular loop of VraG in activation of the membrane sensor GraS in a cystic fibrosis MRSA strain differs in nuance from the CA-MRSA strain JE2.
Regulation of neutrophil myeloperoxidase inhibitor SPIN by the small RNA Teg49 in Staphylococcus aureus.
Benefit-Risk Analysis of Upadacitinib Compared with Adalimumab in the Treatment of Patients with Moderate-to-Severe Rheumatoid Arthritis.
Journal Club: Efficacy of Tocilizumab in Early Systemic Sclerosis-Related Interstitial Lung Disease.
HLA-DRB1 risk alleles for RA are associated with differential clinical responsiveness to abatacept and adalimumab: data from a head-to-head, randomized, single-blind study in autoantibody-positive early RA.
Differential Enhancement of Neutrophil Phagocytosis by Anti-Bactericidal/Permeability-Increasing Protein Antibodies.
Killing three birds with one BPI: Bactericidal, opsonic, and anti-inflammatory functions.
Bactericidal/Permeability-Increasing Protein Preeminently Mediates Clearance of Pseudomonas aeruginosa In Vivo via CD18-Dependent Phagocytosis.
The extracellular loop of the membrane permease VraG interacts with GraS to sense cationic antimicrobial peptides in Staphylococcus aureus.
Upadacitinib in Rheumatoid Arthritis: A Benefit-Risk Assessment Across a Phase III Program.