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LE Magazine October 2001

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The Benz Lab—cancer research at The Buck Institute

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Christopher Benz, M.D.
Professor and Director of the Program on Cancer and Developmental Therapeutics
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H. Michael Ellerby, Ph.D.
Assistant Professor
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Simon Melov, Ph.D.
Assistant Professor
Work in the Benz lab
seeks to understand an interesting paradox: when we age, our cells age, too, and begin to malfunction and break down more quickly than our bodies can repair them; but when cells become cancerous, as they often do with age, they become immortal and grow uncontrollably.

Cancer is a disease of aging. While only 207 out of every 100,000 people under age 65 develop cancer, 2,261 out of every 100,000 people over 65 develop some form of this disease. Breast cancer is among the most common and most feared of the cancers.

Christopher Benz, M.D., is an internationally recognized expert on breast cancer research and therapy. Before starting his Benz Lab at The Buck Institute, he worked as a senior attending oncologist at the UC San Francisco Comprehensive Cancer Care Center, where he still holds a position as an adjunct professor. The research Dr. Benz is engaged in today has been built on almost two decades of study directed at finding molecular strategies for improvement of cancer diagnosis and treatment.

Work in the Benz lab seeks to understand an interesting paradox: when we age, our cells age, too, and begin to malfunction and break down more quickly than our bodies can repair them; but when cells become cancerous, as they often do with age, they become immortal and grow uncontrollably. Dr. Benz and his research associates seek to find the common molecular and cellular defects that these seemingly divergent processes (cancer and aging) share.

Modern chemotherapy drugs are incredibly toxic, especially to the less resilient body of an older person, and cancers often develop resistance to chemotherapy agents that initially work to slow disease progression. Research in the laboratory of Michael Ellerby, Ph.D. is focused on finding new, non-toxic therapies for cancer. In order to grow and spread, tumors must develop a network of blood vessels. Dr. Ellerby is researching the potential usefulness of lab-created “Hunter-Killer peptides,” proteins designed to selectively target and destroy the cells that make up tumor blood vessels.

In a study published in the September, 2000 issue of Nature Medicine, Dr. Ellerby describes the biological action of these Hunter-Killer peptides. One component guides the peptide into cells that are in the process of forming tumor blood vessels; research so far has shown that the other component spares normal cells, but kills off the targeted cells. Currently, Dr. Ellerby is engaged in a search for yet more effective and less toxic versions of these peptides.

Free radicals and mitochondrial function

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Gordon J. Lithgow, Ph.D.
Associate Professor
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David G. Nicholls, Ph.D.
Professor of Mitochondrial Physiology
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David Greenberg, M.D., Ph.D.
Professor and Vice President of Special Research Programs
The laboratories at the Buck Institute house some of the most advanced techniques and equipment available for the purposes of medical research. Those labs are directed by expert technologists who support research teams in using these invaluable tools.

Before helping to found The Buck Institute, Simon Melov, Ph.D. was an assistant professor at Emory University’s Center for Molecular Medicine. Today, he participates in the Gordon Conference on Oxidative Stress and Disease, and is on the editorial board of two peer-reviewed gerontology journals. His research focuses on the mitochondria, tiny “engines” that make energy within cells. Mitochondria create free radicals in the process of metabolizing fuel, and if inadequate antioxidant reserves are present, those free radicals can damage or destroy the mitochondria or the entire cell. The effects of free radical stress—also called oxidative stress, because free radicals can only be formed in the presence of oxygen—have been strongly associated with aging and age-related diseases. Dr. Melov’s research goal is to determine how much of a role mitochondrial oxidative stress plays. In his most recent work, he examined the effects of synthetic antioxidant compounds on mice incapable of producing the mitochondrial antioxidant SOD (superoxide dismutase). Without the antioxidant compounds, the mice died of heart disease within days of their birth; with the SOD-like antioxidant, they lived much longer.

Gordon Lithgow, Ph.D., is the founding editor of the journal Ageing Cell, and has authored and contributed to numerous publications and received prestigious scientific awards for his research. As one of The Buck Institute’s newest staff members, he collaborated with Dr. Melov and Eukarion researchers on studies showing that synthetic catalytic scavengers could lengthen the life span of nematodes. His research focus has been on the link between stress and aging; he has found that animals’ responses to stress strongly influence the length of their lives.

David G. Nicholls, Ph.D., once the head of the Department of Pharmacology and Neurosciences at Dundee University in Scotland, is a founding faculty member of The Buck Institute. He is one of the world’s most respected experts on the subject of mitochondrial physiology. The research he is conducting today builds on the understanding that mitochondrial dysfunction plays an important role in the death of nerve cells in neurodegenerative disease and stroke, as well as in heart damage during heart attack. Dr. Nicholls is also studying the role of excitotoxicity in neurodegenerative disease. Excitotoxicity describes the rapid release of the excitatory neurotransmitter, glutamate, into nervous system tissues, causing nerve and brain cells to be literally excited to death.

Stroke research

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Neurologist David Greenberg, Ph.D., is a founding faculty member of The Buck Institute. Prior to be-ginning his research there, he was an attending neurologist and professor at the University of California, San Francisco and the University of Pittsburgh. His research seeks to understand the cause of cell death during stroke, with the eventual goal of preserving brain function in victims of stroke and similar disorders. His team is also studying how reduction of oxygen supply to the brain encourages the growth of new blood vessels, in hopes of developing a treatment protocol incorporating the administration of VEGF (vascular endothelial growth factor) to reduce the extent of brain damage by re-establishing blood flow to oxygen-starved tissues. Dr. Greenberg’s research also incorporates the study of cannabinoids, substances produced by nervous system tissues in response to injury; there is some evidence that cannabinoids could help prevent stroke. In addition to his research duties, Dr. Greenberg directs the training program for junior researchers and coordinates educational programs for scientists as well as laypeople who live in the San Francisco Bay area.

Cutting-edge laboratory technology

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Mark W. Eshoo, Ph.D.
Director of Genomics
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Bradford W. Gibson, Ph.D.
Professor and Director of the Chemistry Core
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Paul C. Goldsmith, Ph.D.
Director, Morphology Core
The Buck Institute for Age Research is a unique research center, staffed by scientists who are working together to extend the healthy years of the human life span through basic biomedical research.

The laboratories at The Buck Institute house some of the most advanced techniques and equipment available for the purposes of medical research. Those labs are directed by expert technologists who support research teams in using these invaluable tools.

Mark W. Eshoo, Ph.D., runs The Buck Institute’s Genomics Core Laboratory. In this laboratory, researchers use DNA microarray technology to identify the genes involved in diseases of aging. The technology behind the work being done in Dr. Eshoo’s laboratory is incredibly complex, but the end result is an easy-to-read visual representation of genetic activity. Many of the scientists working in the labs of The Buck Institute use Dr. Eshoo’s DNA microarray technology in their work.

Bradford W. Gibson, Ph.D., specializes in the fields of mass spectrometry and structural biology. He currently is working with Dr. Vivian Hook, using these techniques to identify biological markers for degenerative diseases.

Paul C. Goldsmith, Ph.D., directs the Morphology Lab. He has been a professor of obstetrics, gynecology and reproductive sciences at UCSF. The Morphology Lab contains equipment—including transmission electron microscopes and computers that can create detailed digital video images—that allows research teams to visualize and study the activity of genes and genetic expression. In his own research, he seeks to better understand the progression of Alzheimer’s disease by identifying the exact causes of nerve cell degeneration.

Vision research

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Since 1989, Buck Institute re-searchers have conducted a study of residents of the Marin County area aged 55 and older. Data gleaned from this population has been used for research projects on age-related depression, memory, medication use and causes of early death. The aim of the latest of these projects, funded by the National Eye Institute and in collaboration with the Smith-Kettlewell Eye Institute, is to better understand the vision changes that occur with aging. From the results of 16 vision tests given to over 2,000 elderly Marin County residents, researchers hope to better characterize age-related visual changes; to identify lifestyle factors related to vision loss with age; and to find ways to use visual changes to predict general health status.

Helping you age more gracefully

The Buck Institute For Age Re-search is a unique research center, staffed by scientists who are working together to extend the healthy years of the human life span through biomedical research. By doing so, they hope to decrease the financial cost of health care for Americans over 65—approximately $400 billion in 1999 and rising as more people enter this age bracket. They also hope to reduce other costs of declining health in senior citizens, such as the loss of quality of life that inevitably affects sick people, and the stresses increasingly falling on adults who care for their ill, elderly parents.

The Leonard and Beryl H. Buck Trust generously donated much of the funds needed to start the Buck Institute, and continues to donate $5.5 million each year towards its operations.


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