Extensive Research Description
The two major areas of research in this group continue to be molecular approaches to immunopharmacology and studies of mechanisms involved in the modulation of cancer chemotherapy. The family of receptors for the immunosuppressive drug cyclosporin A, termed cyclophilins, is being characterized. Recently, a new member of this family, cyclophilin-40, has been discovered and its biological role is now being explored by the means of site directed mutagenesis and truncation studies. The finding that CyP-40 forms a dimeric complex with heat shock protein 90 is being examined at the structural level by 2D-NMR and in regard to the presence of both proteins in steroid receptors. In the nucleoside transport area, a Na+-dependent active transport mechanism found in several normal tissues but not neoplastic cell lines is being examined in human and other tissues. Changes in this physiological function with cell differentiation are being explored at the molecular level. The role and function of uridine phosphorylase in normal and tumor tissues are under investigation. Clinical studies on BAU, an inhibitor of uridine phosphorylase, as a modulator of 5-FU therapy of colon cancer are in progress.