Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Beavo, Joseph A.
Location University of Washington
Primary Field Physiology and Pharmacology
 Election Citation
Beavo unraveled a complex web of phosphodiesterase isoenzymes that metabolize the second messengers cyclic AMP and cyclic GMP and thereby terminate the action of many hormones. His work implicated these enzymes in novel cellular regulatory pathways and defined the structure and pharmacological properties of the phosphodiesterase enzyme family.
 Research Interests
My research group is interested in the control of signal transduction by cyclic nucleotide second messengers in the cell. More specifically, we investigate the roles of cyclic nucleotide phosphodiesterases in controlling the duration and amplitude of cyclic AMP and cyclic GMP signals. We have found that there are a large number of different isozymes of phosphodiesterase present in most tissues and have helped to show that many different drugs and hormones differentially regulate individual isozymes within this group. Among these are hormones like insulin and adrenalin and drugs like caffeine and theophylline. Studies on the identification, expression, and isolation of individual isozymes of phosphodiesterase have led to a better understanding of their structural, functional, and kinetic properties. Our recent work is focused on the roles of specific phosphodiesterases in the transduction of odorant signals in olfactory sensory neurons, of light signals in retinal photoreceptors, and of antigen signals in the immune system. The realization that different phosphodiesterase regulate cyclic nucleotide levels has increased interest in finding selective inhibitors for each isozyme. A number of isozyme selective posphodiesterase inhibitores are now beginning to be evaluated clinically for treatment of such diverse diseases as hypertension, congestive heart failure, impotence, and inflammation.

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