Caltech Biologist Receives America’s Most Distinguished Prize in Medicine

Alexander Varshavsky, Ph.D., whose landmark discoveries transformed the understanding of how cell behavior impacts diseases including cancer, autoimmune disorders and other illnesses, has been selected to receive the prestigious Albany Medical Center Prize in Medicine and Biomedical Research for 2014.

Dr. Varshavsky is the Howard and Gwen Laurie Smits Professor of Cell Biology at the Caltech. He received this award in recognition of the seminal discoveries he made on intracellular protein degradation.

The $500,000 award has been given annually since 2001 to those who have altered the course of medical research and is one of the largest prizes in medicine and science in the United States. It will be formally awarded on May 21 during a celebration in Albany, NY, at Albany Medical Center.

Dr. Varshavsky is best known for his discoveries related to fundamental aspects of cellular mechanisms that control such vital processes as cell growth and division, responses to stress, and many other biological processes. His insights into what is known as the “ubiquitin system of intracellular protein degradation” underlie one of most promising and active avenues for development of new drugs for treating cancer, neurodegeneration syndromes, autoimmune disorders, and other major diseases.

It has been estimated that studies focused on the ubiquitin system and regulated protein degradation encompass 30 to 40 percent of all biomedical research worldwide.

James J. Barba, president and chief executive officer of Albany Medical Center and chair of the National Selection Committee, said, “To say he is one of the foremost researchers of our times is an understatement. Dr. Varshavsky’s numerous stunning discoveries in the laboratory over more than three decades have already led to new drugs to treat blood cancer, and hold promise for more treatments for so many devastating diseases. Today, the results of his work are standard in biology classes and a solid foundation in biomedical research.”

“Dr. Varshavsky’s discovery of the biological regulation by intracellular protein degradation and its central role in cellular physiology is a singular contribution to biomedical science that can only be described as monumental,” said Sir Michael Berridge, a Fellow at the Babraham Institute, a foremost molecular signaling laboratory in Cambridge, U.K. “It is very rare for one person to have made so many fundamental biological discoveries, which continue to the present day.”

According to Jeremy W. Thorner, professor of biochemistry and molecular biology at the University of California, Berkeley, “Varshavsky is, without doubt, one of the most gifted and uniquely talented scientists of the modern era. He could have chosen to apply his characteristic ingenuity and cleverness to any field, but it is to his very great credit that at the time protein destruction was treated with a yawn by most biologists he saw a fertile field that held great potential for unraveling many of the mysteries of biological systems.”

The Albany Medical Center Prize was established in 2000 by the late Morris “Marty” Silverman, a New York City businessman and philanthropist who grew up in Troy, N.Y., to honor scientists whose work has demonstrated significant outcomes that offer medical value of national or international importance. A $50 million gift commitment from the Marty and Dorothy Silverman Foundation provides for the prize to be awarded annually for 100 years.

In total, 21 world-renowned investigators have been recipients of this prestigious award. Three previous Nobel Prize winners have been among the ranks of researchers honored, and five Albany Prize recipients have gone on to win the Nobel Prize, including stem cell scientist Shinya Yamanaka, M.D., Ph.D.; Elizabeth Blackburn, Ph.D., who discovered the molecular nature of telomeres; Bruce Beutler, M.D., and the late Ralph Steinman, M.D., for their discoveries regarding the detailed workings of the immune system; and Robert Lefkowitz, M.D., for his work on cell receptors.

Over more than three decades of studies, initially at the Massachusetts Institute of Technology (MIT) and later at Caltech, Dr. Varshavsky’s laboratory has made discoveries and inventions that encompass a broad range of subjects in molecular biology, including the path-breaking discovery of the biology of the ubiquitin system.

The human body is made up of cells that have the capacity to differentiate into the entire range of body parts and systems. Cells proliferate and regenerate in response to numerous physiologic stimuli, but they also die as part of their normal life cycle. Cells express many proteins, including ubiquitin, a small cellular protein first identified in the 1970s. Its role appeared to be to target other proteins for destruction, but neither the importance of this system for protein degradation in living cells nor its specific biological functions were known.

In the early 1980s, fascinated by this system’s implications, Dr. Varshavsky started working in this field—one of a very few at the time. Through ingenious genetic and biochemical studies with mammalian cells and yeast, his laboratory was the first to show that the ubiquitin system mediates the bulk of protein degradation in living cells, and that it was directly linked to the cell cycle regulation as well as to several other major processes, including stress responses and DNA repair.
One important treatment resulting, indirectly, from Dr. Varshavsky’s discoveries is bortezomib, a drug used to treat patients with multiple myeloma and lymphoma. Many other drugs that rely on his insights, including those to treat Alzheimer’s, Parkinson’s, and ALS, among others, target other specific enzymes of the ubiquitin system and are either in clinical trials or in research and development by pharmaceutical and biotechnological companies.

The first ‘wave’ of his discoveries that began in the early 1980s, with Dr. Varshavsky’s demonstration that the ubiquitin system is essential for protein degradation in living cells, ‘ended’ around 1990, by which time he had also discovered the first degradation signals in short-lived proteins, the first biological functions of the ubiquitin system, the first specific polyubiquitin chains, and the first genes that encoded critical components of this system.

In his Caltech laboratory, Dr. Varshavsky continues to work in this biomedical field, with an emphasis on the N-end rule pathway, a fundamental part of the ubiquitin system that his laboratory discovered in 1986 and has been studying ever since. Over the last two decades, these and related studies by the Varshavsky laboratory led to many other discoveries, some of which are directly relevant to human diseases and suggest new avenues for their therapy.

For a biography and downloadable photos of Dr. Varshavsky and more information on the Albany Medical Center Prize in Medicine and Biomedical Research, go to: www.amc.edu/Academic/AlbanyPrize.