Ege Kavalali, chair of the Department of Pharmacology at Vanderbilt University School of Medicine Basic Sciences, wants to know how the billions of cells in our brains talk to each other all day.
The William Stokes Professor of Experimental Therapeutics studies the principles of higher-order brain function by investigating how neurons-the cells that carry information through the brain-communicate across synapses, the small gaps between neurons where signals are passed. His work helps shed light on neurological and neurodevelopmental conditions, and how a drug like ketamine actually works to rapidly treat depression.
Kavalali's interest in science took shape early. His mother, a natural product chemist, was a faculty member in the Department of Pharmacology at Istanbul University. But it wasn't neuroscience that captured him initially; he was more into electricity.
"Being a scientist was very attractive from the very beginning, but not necessarily neuroscience or the brain," Kavalali said. "For my undergrad, I studied electrical engineering, and I took a lot of courses in physics."
FROM ELECTRICAL ENGINEERING TO ELECTROPHYSIOLOGY
As an engineering student at Istanbul's Boğaziçi University, his interest started to drift toward experimental neurobiology, in particular, electrophysiology-how excitable tissues like neurons and muscles communicate using electrical signals.
"You do electrical measurements of membrane currents-things like that, and work on ion channels," Kavalali said. "This was quite intriguing to me. It was like, oh my God, I can apply cutting-edge electrical engineering principles and concepts into studying cells and living things. Having a background in electrical engineering was an introduction into what I do today."
Kavalali left Turkey for New Jersey in the early '90s to begin a biomedical engineering Ph.D. program at Rutgers University. He worked with renowned electrophysiologist Mark Plummer, freshly recruited from Harvard, to develop an electrophysiology lab.
"I never actually officially studied biology. I found a mentor, and I was very lucky to study and measure these tiny currents going through membranes. It's exactly what I wanted to do."
After completing his Ph.D. in 1995, Kavalali started his postdoc at Stanford University within the Department of Molecular and Cellular Physiology, mentored by the esteemed Richard W. Tsien. Then he became a faculty member at the University of Texas Southwestern Medical Center in Dallas, where he spent 19 years before coming to Vanderbilt.
GETTING DOWN TO BASICS
At the Kavalali Lab, he and his team focus on the basics-how brain function and behavior are shaped by the way our neurons communicate. His main lab differs from a classical life science research lab-there are no benches or people with pipettes. Instead, Kavalali Lab members use Faraday cages, microscopes and amplifiers to measure how neurons and synapses function.
"We're looking more at the molecular level," Kavalali said. "We manipulate neurons and synapses in multiple ways-electrically, optically and, of course, molecularly. And then we measure their function using electrical and optical signals. It's a very microscale physiology lab. We're studying physiology, but at a very reductionist level."
One outcome of Kavalali's research is a better understanding of how conditions like severe epilepsy, developmental delay and autism-all linked to mutations in synaptic proteins-take root long before they show up as a diagnosis.
"A lot of these diseases start at the very molecular level, so we can actually elucidate that and find out what they do at the synapse," Kavalali said. "And of course, we can look into how drugs work too. We're looking into a lot of these rapidly acting antidepressants-what do they actually do?"
Ketamine is one of them; it has been proven to treat depression at remarkable speed.
"These are people who've been treatment-resistant to depression for decades," Kavalali said. "Then they take ketamine, and suddenly they feel better than they ever have. But what is happening at the synaptic level? We're trying to figure out what kind of plasticity ketamine is eliciting."
For his work illuminating how brain cells communicate, Kavalali was elected a fellow of the American Association for the Advancement of Science, the renowned scientific society behind the Science family of journals.
"There are remarkable things about the brain, right? We have our neurons pretty much for decades, and they're still very dynamic till the very end for most of us," Kavalali said.
"And how is this maintained? How does this system process and store information? How can we have such crisp memories of details? There is so much more to understand how this works so that we can then find out what happens when it doesn't work. There's a lot more to do, and that's exciting."
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