William F. C. RigbyProfessor | Lebanon, New Hampshire
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.