Society for Endocrinology Dale Medal Lecture
Wylie Vale, Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, San Diego, California, USA Abstract
Wylie Vale is the Helen McLoraine Professor of Molecular Neurobiology and Head of the Clayton Foundation Laboratories for Peptide Biology at the Salk Institute for Biological Studies, where he is currently Chair of the Faculty. He is also an Adjunct Professor of Medicine at the University of California at San Diego. Vale and collaborators have published more than 700 peer-reviewed papers, including more than 50 in Nature and Science. They have discovered or co-discovered over a dozen molecules critical to neuroendocrine and neural signaling, including Corticotropin Releasing Factor (CRF), three urocortins, two CRF receptors, CRF binding protein, Growth Hormone Releasing Factor, activin and activin receptors. They have established the neuroendocrine significance of these hormones and revealed novel actions within the brain and elsewhere. For example, in 1981, Vale's group characterized CRF, which is a key regulator of many of the neuroendocrine, immune, autonomic and behavioral responses to stress. They subsequently cloned the first CRF receptor as well as a modulatory binding protein. The cloning of CRF-R2 led to the discovery of three new peptides, urocortin-1, -2 and -3, which are likely ligands for this receptor and that have powerful effects on the brain, heart, gastrointestinal tract and other organs.
He and colleague Jean Rivier have developed pharmacologic agonists and antagonists of gonadotropin releasing factor (GnRH), GRF and CRF. Such analogs and the native peptides have been important investigational tools used to address important physiological questions. Their prototype CRF antagonist has been used in their program and by many others to establish the integrative role played by CRF in mediating numerous aspects of the stress response; results with this antagonist together with physiological, pathophysiological studies and clinical observations provided the proof of concept leading several pharmaceutical companies to launch programs directed towards the development of CRF antagonists which would be used for the treatment of certain affective disorders. He is a co-founder and member of the Board of Directors of Neurocrine Biosciences, which has programs targeting CRF receptors.
His group purified activin, a member of the TGF-beta family with pleotropic local roles regulating reproduction, hematopoiesis, carcinogenesis, cardioprotection and neuroprotection. Vale and colleagues cloned the activin receptor, the first receptor for a member of the TGF-beta family and the first vertebrate receptor serine kinase. Recently his group has identified the proteoglycan, betaglycan, as a co-receptor for inhibin and the oncogene, cripto, as a modulator of activin signaling.
He is President of the International Society of Endocrinology, Past President of the Endocrine Society and a past member of the Council of the National Institute for Diabetes, Digestive and Kidney Diseases. He is a recipient of many awards and lectureships including the Van Meter-Armour Prize (American Thyroid Association), the Albion O Bernstein, M.D. Award (New York Medical Society), the Astwood Award Lectureship (Endocrine Society), the Vincent du Vigneaud Award (American Peptide Society), the Transatlantic Lecture Medal (British Endocrine Society), the Clinical Lectureship Award (British Royal Society of Medicine), and the Contributions to Pituitary Disease Award (Pituitary Society), the Koch Award (Endocrine Society) and the IPSEN Prize for Endocrine Communication. He has been elected to the American Academy of Arts and Sciences, the Institute of Medicine and the National Academy of Sciences (U.S.).