April 26, 2007
Investigator honored for his pioneering discovery of nuclear hormone receptors
Investigator honored for his pioneering discovery of nuclear hormone receptors
La Jolla, CA – Ronald M. Evans, Ph.D., Professor in the Salk Institute’s Gene Expression Laboratory and a Howard Hughes Medical Investigator, has been named a recipient of the 2007 Albany Medical Center Prize in Medicine and Biomedical Research – America’s top prize in medicine.
Evans is being honored for his pioneering discovery of nuclear hormone receptors. He shares this year’s award and the $500,000 prize with co-recipients Dr. Robert J. Lefkowitz, James B. Duke Professor of Medicine and Howard Hughes Medical Institute Investigator at Duke University Medical Center in Durham, N.C.; and Dr. Solomon H. Snyder, Distinguished Service Professor in the Department of Neuroscience at Johns Hopkins School of Medicine in Baltimore, Md. Each of their groundbreaking discoveries of how receptors transmit signals from hormones, drugs and other stimuli to trigger action within the cell helped give rise to a new and rapid phase of drug development, including many of today’s most commonly used prescription drugs.
“The discoveries by Drs. Lefkowitz, Snyder and Evans of how receptors function unlocked the mystery of how all types of hormones and neurotransmitters affect cellular activity. These innovations unleashed a revolution within the pharmaceutical industry that allowed researchers to develop drugs which parodied the effects of these naturally occurring substances,” stated James J. Barba, president and chief executive officer of the Albany Medical Center, who chaired the National Selection Committee.
“Together, their work has led to the development of countless prescription drugs used to treat a wide variety of ailments and conditions from coronary artery disease to schizophrenia and other common psychological illnesses, to breast and ovarian cancer, atherosclerosis, asthma, arthritis and diabetes,” he said.
Among the new drugs that evolved from their work are the next generation of better, safer and more effective beta blockers, cortisone, antihistamines, anti-depressants, estrogens, androgens, contraceptives, insulin sensitizers and obesity pills, Barba added.
While Lefkowitz and Snyder focused on receptor activity on the outer membrane of cells, Evans investigated the workings of a more secretive receptor, one that was hidden inside the cell itself, typically deep within the nucleus. His receptor would come to be known as the nuclear hormone receptor.
For Evans, whose stealthy hormones had little difficulty penetrating the cell membrane, his challenge was to figure out how they triggered cell activity once they reached the interior. Evans demonstrated that the invading hormones, after finding their intracellular receptors in the nucleus, latched onto the chromosomes to switch on precise genetic networks. In effect, they act like molecular “software” to control the “hardware” of the genome.
Evans’ seminal discovery occurred in 1985 when he successfully cloned the first nuclear hormone receptor, the human glucocorticoid receptor. This action would soon lead to the finding of a superfamily of nuclear hormone receptors, all with similar molecular and genetic structures.
Interestingly, his superfamily of nearly 50 nuclear receptors can function like a car with forward, neutral and even reverse activities – allowing the development of unique classes of drugs. The impact on pharmaceutical research would dramatic as the industry could now target a whole new generation of therapies.
Today, Evans’ nuclear hormone receptors are among the most widely investigated group of pharmaceutical targets in the world. Among the drugs that are designed to work in tandem with them are glucocorticoids – cortisone, cortisol and other variations – found in inhalers to treat asthma and also used in the treatment of arthritis, rheumatism, and in the suppression of other inflammatory and allergic disorders; contraceptives; estrogens for hormone replacement therapy; antiestrogens to treat breast and ovarian cancer; androgens, anabolic steroids and antiandrogens for prostate cancer.
More recently, Evans has identified receptors that are targeted by drugs to treat type 2 diabetes and that play a pivotal role in helping to lower sugar levels and remove cholesterol from the body. Earlier this decade, Evans identified the receptor to create the first genetically engineered mice with increased endurance for long-distance running. These marathon mice hold out promise for treating children with degenerative muscle disease as well as helping the growing numbers of overweight people burn more calories faster.
The Albany Medical Center Prize is the largest prize in medicine in the United States and second worldwide to the Nobel Prize in Physiology and Medicine. The annual Prize – announced each spring – has been created to encourage and recognize extraordinary and sustained contributions to improving health care and promoting biomedical research with translational benefits applied to improved patient care.
The Prize was founded by Morris “Marty” Silverman, who passed away in January 2006 at the age of 93. Silverman endowed the Albany Prize in November 2000 with a $50 million gift commitment to Albany Medical Center.
Albany Medical Center is one of only 125 academic health sciences centers in the nation and the only such health care institution in northeastern New York. With 6,500 staff members, this leading not-for-profit health care institution constitutes the largest private employer in Albany. It includes one of New York’s largest teaching hospitals, the Albany Medical Center Hospital (founded in 1849); one of the nation’s oldest medical schools, the Albany Medical College (founded in 1839); and one of the Capital Region’s most active fundraising organizations, the Albany Medical Center Foundation, Inc.
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