Dr. Beavo received his Ph.D. in Physiology at Vanderbilt where he worked with Drs. Earl Sutherland and Joel Hardman on regulation of cyclic nucleotides. He then did postdoctoral work at U.C. Davis where he worked with Dr. Edwin Krebs on cAMP-dependent protein kinase. He then moved to the Department of Pharmacology at the University of Washington where he is currently a Professor.
Dr. Beavo is a member of the National Academy of Sciences. Dr. Beavo's research group investigates the role of cyclic nucleotide phosphodiesterases (PDEs) in controlling the amplitude and duration of cyclic AMP and cyclic GMP signaling pathways. There are a large number of different isozyme families of PDEs that are differentially regulated by drugs and hormones. Many were first discovered and studied in this laboratory.
Much of his recent work has been to determine the physiological reasons for the existence of so many isozymes and to understand mechanistically how they function. In order to understand the mechanisms by which different phosphodiesterases are reg ulated and influence cyclic AMP and cyclic GMP, several different general approaches have been and are being used. These include structural, functional, and kinetic properties of the isolated isozymes. Another related approach has been to develop isozyme specific probes to each phosphodiesterase and utilize them to study localization, function and regulation in crude systems and in intact cells. These include monoclonal antibodies, antisense mRNAs, siRNA, and various drugs.
An important new area of research is to develop methods for studying PDE function in specific sub-regions of the cell. He has also utilized gene disruption studies as a mechanism of determining function. Taken together these approaches have yiel ded at least a partial understanding of the structure, regulation and function of these enzymes in the cell. Particular systems of current interest include the roles of PDEs in inflammation,pulmonary vascular function, cardiac hypertrophy, and steroidogenesis. He also has a major project on the role of cyclic nucleotides and PDE inhibitors the cardiac effects of muscular dystrophy.