April 5, 2006

Salk scientist Ron Evans wins 2006 Gairdner Award for his discovery of hormone sensors

Salk News

Salk scientist Ron Evans wins 2006 Gairdner Award for his discovery of hormone sensors

La Jolla, CA – Ronald M. Evans, Ph.D., professor and head of the Gene Expression Laboratory of the Salk Institute for Biological Studies, has been named a 2006 winner of the prestigious Gairdner Award for his pioneering research into nuclear hormone receptors.

The Gairdner, Canada’s highest scientific honor, recognizes medical science leaders whose accomplishments have advanced the frontiers of knowledge. “The Gairdner Award in Canada is comparable to the Lasker Award in the United States, both being the highest scientific honors in their respective countries and often the precursors to the Nobel Prize,” said Dr. Richard Murphy, President and CEO of the Salk Institute. Dr. Evans received the Lasker Award for Basic Medical Research in 2004 and, in 2005, the Grande Médaille d’Or, France’s highest scientific honor.

Dr. Evans’ work brought to light the common mechanism by which a diverse group of hormones and vitamins – steroid hormones, thyroid hormones, and fat-soluble molecules such as vitamins A and D – control the body’s metabolism, development and reproduction. Scientists had known since the early 1900s that hormones directed organ physiology, but, until Dr. Evans’ discovery, they had no idea how the minute amounts of hormones produced by the body actually triggered the changes.

Because nuclear receptors wield such physiological power, their discovery provided a multitude of targets for clinical scientists to develop new, more effective, and safer drugs. As a result, Dr. Evans’ technology has been used to discover more than half a dozen drugs for cancer, diabetes and heart disease, with many more on the way.

In 1985, Dr. Evans discovered how cortisol, a steroid hormone that regulates glucose metabolism, accomplishes its mission. Like a messenger carrying an urgent message, cortisol sweeps into a cell’s nucleus where it is met by molecules called nuclear receptors. They grab the cortisol molecules and together they clamp down in specific places on the chromosomes, where they tweak the activity of genes.

The discovery of the receptor for cortisol provided the much-needed code to hormones’ puzzling mode of action and opened the door to future discoveries. Following his discovery, Evans, and others in his field began hunting for more hormone sensors by using the cortisol receptor gene as a blueprint.

To date, researchers have turned up nearly 50 related nuclear receptors that function as on/off switches for genes as soon as they bind to messenger molecules. Prior to Dr. Evans’ research it was not known that fat-soluble vitamins, steroid hormones and dietary fats use a common strategy to communicate with genes inside a cell’s nucleus.

Two of the receptors that Dr. Evans discovered, PPAR gamma and PPAR delta, play key roles in regulating the storage and burning of fat. Mice that are genetically engineered to produce an overactive version of PPAR delta burn dietary fat at very high rates and have stronger slow-twitch muscle mass. When placed on a rodent-sized treadmill, these genetically engineered “marathon mice” run twice as far as their normal counterparts.

Dr. Evans’ lab’s research on vitamin A signaling has been key to defining the vitamin’s role as a gene regulator and its central role in orchestrating embryonic development and adult physiology. Following these discoveries, vitamin A therapy became a “magic bullet” for treating people with acute promyelocytic leukemia.

Evans also discovered that the anti-diabetic drugs Actos and Avandia, the only approved drugs known to make body cells more sensitive to insulin, work by activating another nuclear receptor, namely PPAR gamma. Many, more potent, members of this drug class are currently under development.

One particular nuclear receptor, also known as SXR (short for steroid and xenobiotic receptor) is responsible for the majority of harmful drug – drug interactions. Since this crucial finding emerged from Dr. Evans’ lab in 1993, pharmaceutical companies increasingly rely SXR screens to improve the safety of new drugs.

Dr. Evans’ current research focuses on deepening our understanding of the molecular basis of obesity-related diseases such as diabetes and syndrome X, a disorder characterized by high blood pressure, heart disease and insulin resistance.

About Dr. Evans:

Born and raised in Los Angeles, Dr. Evans earned his bachelor’s degree in bacteriology and his doctorate in microbiology and immunology from the University of California, Los Angeles. After completing a postdoctoral research fellowship at Rockefeller University in New York, he was recruited to the Salk Institute in La Jolla. A faculty member at Salk since 1978, Dr. Evans is a Howard Hughes Medical Institute Investigator and holds the Salk Institute’s March of Dimes Chair in Developmental and Molecular Biology.

Dr. Evans has received many honors in addition to the Gairdner Award. Last year, he received the Grande Médaille d’Or (Grand Gold Medal), France’s highest scientific honor. In the fall of 2004, he shared the Lasker Award for Basic Medical Research with two other scientists. He has been elected to the National Academy of Science, Institute of Medicine as well as the American Academy of Arts and Sciences. He is also the past recipient of the California Scientist of the Year Award; General Motors Sloan Award for Cancer Research; March of Dimes Prize in Developmental Biology; Bristol-Myers Squibb Award for Distinguished Achievement in Metabolic Research; and the Keio Prize in Medicine. Dr. Evans’ published studies are among the most frequently cited by the scientific community worldwide, according to the nonprofit Institute for Scientific Information.

About the Gairdner Foundation International Award:

The Gairdner is one of the most prestigious awards in all of science. Founded by the late Toronto businessman James Gairdner and now in its 47th year, the Gairdner Award recognizes medical scientists “whose seminal discoveries and major scientific contributions constitute tangible and significant achievement in biomedical sciences.” Since its inception in 1959, 279 scientists have received the Gairdner, 65 of whom have gone on to win a Nobel Prize. The 2006 awardees were announced in Toronto today and will receive their awards at a gala dinner in October. For more information, go to: www.gairdner.org.

About the Salk Institute for Biological Studies:

Internationally renowned for its groundbreaking basic research in the biological sciences, the Salk Institute was founded in 1960 by Dr. Jonas Salk, five years after he developed the first safe and effective vaccine against polio. The Institute’s 59 faculty members are scientific leaders in the fields of molecular biology, neurosciences and plant biology.

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