Ronald M. Evans
Wolf Prize Laureate in Medicine 2012
Ronald M. Evans
Affiliation at the time of the award:
The Salk Institute, USA
“for discovering the gene superfamily encoding nuclear receptors and elucidating the mechanism of action of this class of receptors”.
Dr. Ronald M. Evans (born in 1949, USA) is best known for his discovery of the superfamily of genes encoding nuclear receptors and for the elucidation of their universal mechanism of action, a process of controlled gene expression that governs how lipophilich hormones, vitamins and drugs regulate diverse developmental and metabolic pathways.
Ron Evans establishes the mechanism by which hormones signal through the nucleus to regulate gene expression, thereby controlling physiology. This was achieved by cloning and characterizing the first nuclear receptor, the glucocorticoid receptor, which produced a blueprint for understanding all nuclear receptors subsequently discovered. Evans went on to mineralocorticoid, thyroid and retinoic acid (Vitamin A) receptors, providing a unifying mechanism by which chemically distinct hormones precisely control a series of genetic switches. Discovery of this superfamily redefined endocrine physiology based on knowledge of receptor structure and function, leading to the prediction of the existence of as yet undiscovered hormonal signaling pathways and the discovery of the first orphan receptor. This led to the development of a technology platform known as “reverse endocrinology”, which then ked Evans to the discovery of the first orphan hormone. Reverse endocrinology helped to launch the rapid evolution of entirely new branches of endocrine physiology and to identify novel molecular targets for therapy.
In summary, Evan’s discoveries on the nuclear hormone receptors define a unitary signaling pathway and a central paradigm for the control of eukaryotic expression. His work establishes a transcriptional basis to physiology and has led to the discovery of completely unrecognized physiologic pathways as well a new generation of drugs for the treatment of cancer, metabolic disease and muscular dystrophies.