, chair of the Department of Pharmacology at , 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鈥攖he cells that carry information through the brain鈥攃ommunicate 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鈥檚 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鈥檛 neuroscience that captured him initially; he was more into electricity.
鈥淏eing a scientist was very attractive from the very beginning, but not necessarily neuroscience or the brain,” Kavalali said. 鈥淔or my undergrad, I studied electrical engineering, and I took a lot of courses in physics.鈥�
FROM ELECTRICAL ENGINEERING TO ELECTROPHYSIOLOGY
As an engineering student at Istanbul鈥檚 Bo臒azi莽i University, his interest started to drift toward experimental neurobiology, in particular, electrophysiology鈥攈ow excitable tissues like neurons and muscles communicate using electrical signals.
鈥淵ou do electrical measurements of membrane currents鈥攖hings like that, and work on ion channels,鈥� Kavalali said. 鈥淭his 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.鈥�
Kavalali left Turkey for New Jersey in the early 鈥�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.
鈥淚 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鈥檚 exactly what I wanted to do.鈥�
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 菠萝视频.
GETTING DOWN TO BASICS
At the Kavalali Lab, he and his team focus on the basics鈥攈ow brain function and behavior are shaped by the way our neurons communicate. His main lab differs from a classical life science research lab鈥攖here are no benches or people with pipettes. Instead, Kavalali Lab members use Faraday cages, microscopes and amplifiers to measure how neurons and synapses function.
鈥淲e鈥檙e looking more at the molecular level,鈥� Kavalali said. 鈥淲e manipulate neurons and synapses in multiple ways鈥攅lectrically, optically and, of course, molecularly. And then we measure their function using electrical and optical signals. It鈥檚 a very microscale physiology lab. We鈥檙e studying physiology, but at a very reductionist level.鈥�
One outcome of Kavalali鈥檚 research is a better understanding of how conditions like severe epilepsy, developmental delay and autism鈥攁ll linked to mutations in synaptic proteins鈥攖ake root long before they show up as a diagnosis.
鈥淎 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,鈥� Kavalali said. 鈥淎nd of course, we can look into how drugs work too. We鈥檙e looking into a lot of these rapidly acting antidepressants鈥攚hat do they actually do?鈥�
Ketamine is one of them; it has been proven to treat depression at remarkable speed.
鈥淭hese are people who鈥檝e been treatment-resistant to depression for decades,鈥� Kavalali said. 鈥淭hen they take ketamine, and suddenly they feel better than they ever have. But what is happening at the synaptic level? We鈥檙e trying to figure out what kind of plasticity ketamine is eliciting.鈥�
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.
鈥淭here are remarkable things about the brain, right? We have our neurons pretty much for decades, and they鈥檙e still very dynamic till the very end for most of us,鈥� Kavalali said.
鈥淎nd 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鈥檛 work. There鈥檚 a lot more to do, and that鈥檚 exciting.鈥�
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