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Pharmacology In the News 



Dr. Joseph A. Beavo (Professor Emeritus of Pharmacology at the University of Washington) will receive the Julius Axelrod Award of the American Society for Pharmacology & Experimental Therapeutics on April 21, 2018 at the EB2018 meeting in San Diego. This prestigious award is named for Nobel Laureate Julius Axelrod, who pioneered studies of the catecholamines epinephrine and norepinephrine (also known as adrenalin and noradrenalin) as neurotransmitters and hormones. The catecholamine neurotransmitters are now known to act through the intracellular messenger cyclic AMP.

Joe Beavo is a world leader in studies of the cyclic nucleotide phosphodiesterase family of enzymes (PDEs), which hydrolyze cyclic AMP and cyclic GMP to terminate their signal transduction in many cell types. Because the catecholamines use these cyclic nucleotides as second messengers in their cellular signaling, Beavo's research accomplishments are especially relevant to the Julius Axelrod Award. This award recognizes both Beavo's major scientific achievements in research on PDEs and his exceptional mentoring of graduate students and postdoctoral fellows, many of whom have become leading researchers in this field.

As a graduate student with Professors Earl Sutherland and Joel Hardman at Vanderbilt in the 1960's, Beavo conducted the most complete analysis of cyclic-nucleotide hydrolysis by PDEs to that time and discovered the inhibitory effects of methylxanthines, such as IBMX, which remain mainstays of G-protein-coupled-receptors and cyclic-nucleotide research even today. As a postdoctoral fellow and research-faculty member with Professor Edwin Krebs in the 1970's, Beavo made major contributions toward understanding the biochemical and molecular properties of cAMP-dependent protein kinase and its regulatory subunits. His work contributed significantly to the Nobel Prize in Physiology or Medicine received by Professors Edwin Krebs and Edmond Fischer for their discovery of protein phosphorylation, protein kinases, and phosphoprotein phosphatases. In his own laboratory at the University of Washington, Beavo returned to the theme of PDEs. Adroitly using biochemical purification methods in conjunction with novel monoclonal antibody approaches, Beavo dissected the different members of the eleven diverse PDE protein families, revealed their differential expression among tissues and cell types in vivo, established their different specificities for hydrolysis of cAMP vs. cGMP, and defined their differential regulation by cyclic nucleotides and by calcium. These seminal discoveries laid the foundation for basic understanding mechanisms of PDE function and regulation and led directly to successful efforts at pharma companies to develop subtype-selective PDE inhibitors as drugs. As a result, milrinone and other PDE3 inhibitors have been used for treatment of acute heart failure; sildenafil (Viagra), tadalafil (Cialis), and other PDE5 inhibitors are famously used for acute treatment of erectile dysfunction, and these drugs more recently are also used for pulmonary hypertension and benign prostate hyperpalsia. Beavo and his colleagues led the way in cloning cDNAs for many PDEs, thereby establishing the molecular relationships among the eleven families of PDE enzymes, defining their diversity of form and function, and providing molecular reagents generously to the field to catalyze many important advances in this research area. He discovered the structural basis for regulation of PDEs through GAF domains. Beavo's work also established the key role of PDEs in cell signaling and regulation in many physiological processes, including olfaction, vision, insulin secretion, smooth muscle cell proliferation, T-cell and macrophage activation, steroidogenesis in the adrenal cortex, and the functions of Leydig cells and Sertoli cells in development of sperm in the testis. Beavo's work pioneered the broad field of PDE research that has greatly advanced our understanding of cell signaling pathways and yielded multiple pharmacological agents of great therapeutic value.

Beavo was elected to the National Academy of Sciences early in his career in 1996, and he has also been a leader of international stature in Pharmacology. He served as Councilor of ASPET from 2000-2008 and ASPET President in 2009. He also served as Associate Editor of Molecular Pharmacology and as an editorial board member of Pharmacological Reviews, the Journal of Biological Chemistry, Proceedings of the National Academy of Sciences, and other prestigious scientific journals.

Beavo has been an exceptional mentor of junior colleagues. He trained 23 graduate students and more than 32 postdoctoral research fellows and visiting junior faculty members. He worked side-by-side with his trainees to establish new methods and guide them in their research, and he nurtured their scientific development as they branched out and pursued independent research projects. Many of his graduate students and postdoctoral fellows moved on to successful careers in academia, pharma, and biotech industries. Examples include Stuart Builder (Director at Genentech, retired), Mark Mumby (Professor at University of Texas Southwestern Medical Center, retired), Harry Charbonneau (Professor at Purdue University), Peter Gillespie (Professor at Oregon Health & Science University), Scott Soderling (Professor at Duke University), and Chen Yan (Professor at University of Rochester).