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Longtime Brain Researcher ‘Driven by Curiosity’

Dr. Alex Dopico’s love of medicine and science has spanned his career and his life. A recent paper on steroids and the cerebral circulation was published in the journal, Nature Communications.

Alex Dopico, MD, PhD, received his first chemistry set from his parents when he was 7 years old. Four years later, they gave him a magazine about the lives of great scientists.

He remembers reading about 19th century British chemist John Dalton and his ideas about atoms and molecules. “With the ingenuity of a child, I thought diseases could be understood at the molecular level,” Dr. Dopico says. “I always wanted to be a scientist.”

Today, Dr. Dopico is the Harriet Van Vleet Chair of Excellence and a professor in the Department of Pharmacology, Addiction Science, and Toxicology at the University of Tennessee Health Science Center.

In his native Argentina, he entered medical school, yet he never lost his love for fundamental research. Dr. Dopico recalls treating cardiovascular and hypertensive patients in the morning and working on research experiments from afternoon into the late night.

After earning first an MD and then a PhD from the University of Buenos Aires, he had a hard decision to make. He felt he could not give his best to his patients or to science by splitting time between the two.

“As rewarding as taking care of patients was, I could not give up the need that I have had since childhood to know and to discover new things,” he says.

Dr. Dopico ultimately chose research and has spent his career fulfilling that need to know. His long-funded research has focused on various aspects of the role of vascular and neuronal ion channels in physiology and disease.

“As rewarding as taking care of patients was, I could not give up the need that I have had since childhood to know and to discover new things.”

Dr. Alex Dopico

His most-recent research resulted in a paper published in the journal, Nature Communications, which publishes high-quality research representing significant advances in the natural sciences.

Dr. Dopico is the principal author of the paper titled, “Progesterone activation of β1-containing BK channels involves two binding sites.” This work deals with steroids and the cerebral circulation. This and related lines of investigation are supported by grants to Dr. Dopico from the National Heart, Lung, and Blood Institute; the National Institute on Alcohol Abuse and Alcoholism; and the National Institute of  Environmental Health Sciences. The goal is to understand the molecular-level abnormalities in the cerebral circulation driven by disease or drug intake, and ultimately, to develop new drugs to counteract these abnormalities.

Through a wide variety of methodologies, from computational chemistry to in vitro and in vivo biological approaches, Dr. Dopico and his team, including longtime collaborator, Anna Bukiya, PhD, professor in the Department of Pharmacology, Addiction Science, and Toxicology, identified a novel molecular site where the steroidal hormone progesterone binds to a protein receptor termed a BK channel, an ion channel located in the brain artery, causing vasodilation or widening of the artery.

This work is a step toward new and more-targeted vasodilators to treat cerebral ischemia or restriction of blood flow, he says.

“It’s very likely that some of the therapeutic effect of progesterone on ischemic events is because this steroid causes local vasodilation,” he says. “We found the reason for progesterone to cause vasodilation. Now, you may say, isn’t it enough to know that it’s a vasodilator? Why go through all the trouble to study where the molecular site of interaction is? The answer is that once you identify and characterize this molecular site as we did, you have the necessary information to develop agents that dock to the site but lack other structural features of progesterone. These may counteract brain ischemia, while lacking progesterone’s hormonal effects, be more selective, act at much lower concentrations, and be more potent.”

Dr. Dopico admits he is still sorting out his lifelong medicine-versus-basic-science dilemma. “As a physician, addressing health issues is a must, yet the curiosity for the unknown remains a fundamental driving force.”