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Alex Dopico, MD, PhD, Chair of Pharmacology at UTHSC, Awarded More Than $1.85 Million Extension Grant to Study Effects of Alcohol on Arteries in the Brain

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Dr. Alex Dopico

Alex Dopico, MD, PhD, Distinguished Professor and Chair of the Department of Pharmacology at the University of Tennessee Health Science Center (UTHSC), has been awarded more than $1.85 million to extend funding for his ongoing research into the effects of alcohol on the brain. His goal is to develop drugs that target the proteins within cells that control the physiological and behavioral changes associated with alcohol intoxication in order to prevent or reverse those effects.

Dr. Dopico has spent more than 20 years researching alcohol’s effects on ion channel proteins in the central nervous system and brain circulation. In early June, he reported a major breakthrough toward developing new drugs to counteract alcohol’s toxicity by targeting the BK channel proteins, or Big-conductance potassium channel proteins, which are present in all excitable tissues and control a variety of physiological processes. Modification of their activity by exposure to alcohol is thought to be a cause of changes in normal physiology by alcohol intoxication.

Dr. Dopico and his team identified for the first time a specific site in the BK channel protein where alcohol is recognized and alters the channel’s function.

“Having found and characterized at the molecular level a site that is rather specific for alcohol recognition, we can now develop small pharmacological agents that interact with that site and antagonize alcohol action on the channel, eventually leading to prevention or reversal of alcohol toxicity,” he said.

A paper by Dr. Dopico and his research team detailing this finding was published recently in the Proceedings of the National Academy of Sciences, one of the world’s most-cited multidisciplinary scientific journals.

In 2009, Dr. Dopico was awarded a 10-year MERIT Award worth a total of $3.6 million from the National Institute on Alcohol Abuse and Alcoholism, a division of the National Institutes of Health, for his alcohol studies, which have particular emphasis on the effects of alcohol on BK channels in excitable cells, such as central neurons and brain arterial smooth muscle. When the first half of that award expired in June, Dr. Dopico received the $1.85 million extension to fund an additional five years of research.

The MERIT Award (Method to Extend Research in Time) program has become a symbol of scientific achievement in the research community. The awards are offered to investigators who have demonstrated superior competence and productivity in their research, and who are likely to continue the outstanding performance. Investigators receiving a MERIT Award have the opportunity to obtain up to 10 years of support in two five-year periods without having to submit frequent renewal applications.

Dr. Dopico’s previous research includes determining that action in the BK channels makes cerebral arteries contract in the presence of alcohol; that cholesterol levels in cell membranes alter alcohol’s action on these channel proteins in cerebral arteries; and that the receptor for caffeine is key in alcohol action on brain arteries.

Dr. Dopico said he is honored to receive the MERIT Award extension that allows him to continue his research. He said identifying the alcohol-recognition site in BK ion channel proteins is “a major finding” that will hopefully impact the development of pharmacotherapeutic agents to treat consequences of alcohol intoxication that affect brain function.

“My job is to find molecular sites and mechanisms by which alcohol affects excitable tissue physiology, and thus agents that fight the consequences of alcohol intoxication in the brain,” he said. “To do that, you need to find the protein sites where alcohol docks or interacts, and we had a very critical breakthrough in the BK channel protein.”

The National Institutes of Health (NIH), the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about the NIH and its programs, visit www.nih.gov.