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AAAS Fellow Berislav Zlokovic is hitting the high notes

AAAS Fellow Berislav Zlokovic could have become a tenor with a medical degree, but as the director of the Zilkha Neurogenetic Institute at the University of Southern California, he is known as the scientist who sings. (Photo: Rebecca Fairley Raney)

For Berislav Zlokovic, life has been full of intriguing choices. Would he study the heart or the brain? Would he focus on neurons or blood vessels? And, perhaps most importantly, would he become a neuroscientist or an opera singer?

He has done a lot of both. But rather than becoming a tenor with a medical degree, Zlokovic is known as the scientist who sings.

Zlokovic chats in cadences acquired during a childhood in Budapest as he speaks about the time he sang with tenor Placido Domingo—or recalls his successful audition with the English National Opera as a young man, and his recent performance of Carmen in San Diego. Although Zlokovic describes his musical biography as "minor, minor, minor," it's clear that the AAAS fellow could talk about the music all day.

"I say, in science, it takes five years to get results. In music, I hit the high notes, and I am happy for two days."

He has a lot to be happy about these days. Zlokovic manages the occasional role on stage in addition to working as director of the Zilkha Neurogenetic Institute at the University of Southern California. The institute employs more than two dozen faculty members and investigators, and it had a budget of $18.5 million in 2013. Research projects center on causes and cures for brain disorders and diseases, including Alzheimer's disease, autism and depression.

Working from a standing desk in a glossy, glassed-in building across from the Keck Medical Center of USC, Zlokovic says he still wonders sometimes how all this happened. It was the music, he is convinced, that helped him make his first significant connection in science.

He was a doctoral fellow at Queen Elizabeth College in London when the chairman of his department unexpectedly invited him for dinner. "He invited me because he knew I could sing," Zlokovic says.

He was introduced to the guests—who included pioneering physiologist Hugh Davson—and after dinner, he sang arias from La Traviata. After that night, Davson and Zlokovic struck up a friendship. Zlokovic would go on to work for Davson, who was entrenched in the study of the blood-brain barrier. The phenomenon occurs in cells in blood vessels, which fit tightly together to prevent harmful substances from entering the brain.

Later, in his own research, Zlokovic examined how the blood-brain barrier controls the delivery of messages in the brain. He found systems in blood vessels that shuttle neuroactive peptides, which are sequences of amino acids. These transport systems, he learned, could have implications for drug delivery as well as the development of disease. (See a review of the research.)

Zlokovic examined the role of these systems in the development of Alzheimer's disease. That research was the first step toward current testing that examines whether the breakdown of the blood-brain barrier in the hippocampus is the first thing that goes wrong for Alzheimer's patients.

His research has garnered some of the biggest awards in the field, including the MetLife Award and the Potamkin Prize from the American Academy of Neurology. Yet the scientist talks with a genuine sense of surprise about how he went from working with a small grant to running a big lab.

"I didn't have any idea I would end up here," he says.

The momentum started in 1997, when the National Institutes of Health renewed a $50,000 grant for more than $7 million. Not long after, Zlokovic heard from businessman Selim Zilkha, who invited the scientist to his home in Bel-Air and asked him what he wanted to do.

"I told him, 'I want to study the longevity of the vascular system as opposed to the neuronal system,' and he said, 'I love that idea.' "

They set up a biotechnology firm together in Rochester, N.Y. Now, in addition to running the lab at USC, Zlokovic works as chairman of the scientific advisory board for ZZ Biotech. The company is developing an experimental drug called 3K3A-APC, which is an altered version of an anticoagulant drug used in stroke patients that, in animal models, has diminished the side effect of brain bleeding. Human clinical trials will start next year.

Zlokovic describes the move into matters of business as a difficult learning curve. He sat down for many frustrating meetings with Zilkha's team of lawyers and MBAs. But he came out of the experience with a new perspective: If you apply industry standards to your lab, with meticulous logging and cataloging, you do better science.

"Science is not business," he says, \"but it has to have a business side.\" 

The other part of business—working with people—came naturally. It takes Zlokovic a long time to make his way through the hallways of the institute. He stops to have a conversation with everyone he sees.

"I love talking to people," Zlokovic says. "I know everybody, what they're doing. I am every day in the lab."