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Alcohol Research Center Receives $8.9 Million Grant to Investigate Genetics of Alcoholism

   Portland, Ore.

The Portland Alcohol Research Center (PARC) will receive $8.9 million over five years from the National Institute on Alcohol Abuse and Alcoholism to continue its search for genes involved in alcohol abuse. The institute (NIAAA) is part of the National Institutes of Health.

This is the center's second five-year grant from NIAAA. The first, for $8.5 million in 1995, established the center at Oregon Health & Science University and the Portland Veterans Affairs Medical Center.

"The renewal grant is gratifying," said John Crabbe Jr., Ph.D., center director, professor of behavioral neuroscience, OHSU School of Medicine, and professor of physiology and pharmacology, VAMC. "It validates our progress in the long, slow march toward our goal: identifying specific genes involved in alcoholism."

Human and animal genetic studies show that a predisposition to alcoholism and drug abuse is partly influenced by genes. Discovering these genetic links would be a step toward helping prevent alcohol abuse in susceptible people. Currently, although genetic risk factors are known, it is impossible to advise anyone about his or her actual level of risk.

Of some 30,000 human genes, only a handful are involved in alcoholism. Targeting individual genes and their functions is a complex process of elimination.

The Portland Alcohol Research Center is one of 15 in the country funded through NIAAA's National Alcohol Research Centers Program. It has a staff of about 100, including 18 scientists at the VA and OHSU and one at Portland State University. Each center pursues one research theme in depth, in turn sharing outcomes with NIAAA's other centers and research programs. For example, PARC's theme is behavioral genomics, while others include the neurobiology of the central nervous system and translational neuroscience.

"Our main thrust is using gene mapping techniques to identify specific areas of chromosomes involved in risk for, and protection against, the bad effects of chronic alcohol on the brain," Crabbe said.

Ernestine Vanderveen, Ph.D., director of the Alcohol Research Centers Program, said the Portland center is exemplary not only for its research, but for its interdisciplinary collaboration, its training opportunities for young scientists, and its outreach to the international scientific community. "They have a number of strengths our institute values," she said.

PARC's research has helped advance the field of alcohol research, she said. "Portland has developed a widely used mouse model for studies conducted within the center and beyond," Vanderveen said. "These models of physical dependence allow researchers to explore mechanisms involved in the brain's adaptation to alcohol."

PARC has achieved many milestones. In 1996, for example, its scientists demonstrated that mutant mice lacking a certain gene were more likely to drink alcohol. The results were published in Nature Genetics. In 1997 PARC researchers reported mapping three gene regions in mice that influence susceptibility to physical dependence on alcohol. The findings were reported in the Journal of Neuroscience. In 1999 they found another gene that appears to confer protection from alcohol withdrawal.

Most recently, in a study presented at the annual meeting of the National Research Society for Alcoholism, PARC scientists report narrowing their search to an even smaller region of mouse chromosome 4 and identifying a specific gene that may influence one aspect of alcoholism -- namely, the severity of alcohol withdrawal symptoms. Two PARC researchers, Kari Buck, Ph.D., assistant professor of behavioral neuroscience, OHSU School of Medicine, and postdoctoral fellow Christoph Fehr, M.D., "are closer to identifying a risk gene for alcoholism than any other group in the world that is chasing genes relevant for substance abuse in animal models," Crabbe said.

The research in Oregon began even before PARC was funded as a center, with early support from an NIH project grant. New research techniques may help speed progress. "After 10 years of effort," Crabbe said, "we find ourselves in the midst of the genomics revolution, where methods, resources, and potential applications are changing so quickly that our new directions include some we could barely conceive at the beginning."

Potential new tools include a high-resolution MRI system that may make it possible to view brain function and even gene expression in the living brain; and mathematical models that may reduce the time required for gene analysis. PARC data were used in a study of such mathematical models reported in Science Magazine in June.

PARC scientists are widely recognized in the field. Three scientists--Tamara Phillips, Ph.D., research scientist, VAMC and professor and vice chairwoman of behavioral neuroscience, OHSU; School of Medicine Deb Finn, Ph.D., associate professor of behavioral neuroscience, OHSU School of Medicine, and research pharmacologist, VAMC; and Buck have been named Outstanding Young Investigator of the Year in past years by the Research Society on Alcoholism.

John Belknap, Ph.D., senior research scientist, VAMC, and professor of behavioral neuroscience, OHSU School of Medicine, is nationally known for his contributions to the statistical methods for ascertaining gene location in animal models. Christopher Cunningham, Ph.D., professor of behavioral neuroscience, received OHSU School of Medicine's 2001 Alumni Scientist Award -- the first year the award has been given to honor an outstanding alumnus. PARC research has contributed to more than 150 papers published in scientific journals.

PARC also is active in public outreach and education about alcoholism, such as Brain Awareness Week in March and National Alcohol Screening Day in April.

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