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Interview with Dr. Andrea Meredith (Humans of Neuroscience)

Dr. Andrea Meredith is a professor at the University of Maryland School of Medicine, who is working on understanding the mechanism by which information is coded in the brain.

What is your current career and involvement in neuroscience and/or psychology?

I am a neuroscientist in basic research and Associate Professor at the University of Maryland School of Medicine. I have been running a federally-funded research lab with students, postdocs, and technicians for 13 years. I teach medical and graduate students neuroscience and the biophysics of ion channels, proteins in the cell membrane that pass electrical currents. My main research interests are to understand how ion channel gating properties - how they open and close to generate electrical currents across cell membranes - regulate information coding in dynamic contexts. We want to understand everything from how time is encoded in the brain, to how seizures are produced.

How and when did you discover your interest in the brain?

When I was in graduate school, they told us that you could snooze through one part of the “core course” if you were a rock star in the lab. Since I was a rock star in the lab, I chose to do so, particularly through the section on immunology. In the first year of grad school, we didn’t really cover much neuroscience (or at least not that I remember), so it wasn’t until I was approaching my second year that it dawned on me: this neuroscience stuff is hard and not well understood. I was hooked on understanding the electrical signals that neurons produced. It turns out that the immune system possesses a staggering complexity of cell types and function; it even uses ion channels to ‘code’ information in membrane potentials or through ion fluxes that regulate immunity. I probably would have been fine either way, but to me, the mechanism of electrical communication, its rapid time-scale, precise methods of measurement, and ability to propagate action potentials in neurons is sheer beauty.

What are some of your biggest achievements?

My goal is to understand information coding in the brain, in particular,  how the brain uses ion channels to control membrane potential and dynamic electrical signaling. In my lab, we combine the genetic manipulation of ion channels with electrophysiology, imaging, and in vivo physiology. Two central goals of the lab are to identify the fundamental biophysical properties of ion channels that cause neurological diseases, and to identify how ion channels pattern action potential activity in the circadian clock of the brain. Our bread-and-butter studies in the lab have made important contributions to understanding how circadian rhythms in excitability are produced in the central ‘clock’ of the brain. These neurons regulate the gating of an ion channel called Big Potassium (K+), better known as BK, in a time-of-day specific manner.

If the ion channel activity is not regulated appropriately according to what time of day it is, the clock’s ability to encode and transmit that time signal is disrupted. This produces disturbances in circadian rhythms in animals, and we’ve observed this in mice: altering their sleep-wake cycle has important implications for whole range of diseases that involve the brain’s clock, from insomnia to stroke, seizure, metabolic disorder, and even psychiatric disorders like depression and addiction. But our biggest achievement may ultimately be applying what we understand about BK channels to people that carry genetic mutations in the gene that encodes that ion channel (KCNMA1). These patients have mutations that cause their channels to ‘gate’ (or open and close) in ways that are abnormal, leading to deranged electrical signaling in the brain, such as seizures. Starting with a little girl with severe paroxysmal dyskinesia who was featured in the NYTimes medical mystery column, ‘Diagnosis,’ there are now about 20+ new patients who have been identified with KCNMA1 mutations. Since no BK channel-selective treatments options currently exist, we have partnered directly with these patients to study how their novel mutations alter BK channel activity. My lab’s efforts were recently highlighted in a documentary produced for Netflix, which included filming in my lab at UMB SOM. We discovered that the ‘Diagnosis’ patient mutation produces an aberrant increase in BK channel gating. We are currently studying several other KCNMA1 patient mutations, and our goal is to discover the ion channel and neurological basis for patient symptoms.

Did you have a role model that influenced your decision to work in STEM?

Having good science teachers primes your interest, but having someone to interact with one-on- one, and who listens to your ideas, is invaluable. For me, that first person in my life to seed my scientific confidence was my undergraduate lab mentor, Marvin Boluyt. I worked for him when I was an undergraduate at the Gerontology Research Center, a division of the National Institute of Aging in Baltimore. He was a relentlessly curious and cheerful scientist of the highest integrity. Not only did he listen to my ideas, but he facilitated me exploring them. He also gave me important feedback that was critical to helping me develop accuracy in my experimental protocols, as well as support when I failed. One time I dropped a gel with some very important samples that had taken a long time to generate. He showed me how to pick up the pieces (literally) and transfer the gel to the membrane. We got the data, albeit with a ‘seam’ down the middle. But he taught me that every problem has a solution, even at the bench.

Is there a scientific topic outside of the brain that you find very fascinating?

Several years ago, we had the opportunity to see the GOES-R satellite launch from Cape Canaveral on an Atlas V rocket. An Atlas V is an impressively big rocket. My brother-in-law Mike worked on the software systems. We got to watch the launch from Banana Creek, near the launch pads where the space shuttle once launched (now SpaceX is there). We had such a great time that I took it as a hobby to explain how the satellites sensors work (it’s a weather satellite) to kids in my daughter’s class. The GOES-R satellites (there will eventually be 4 of them) will significantly improve our ability to make accurate earth and space weather forecasts. The sensors have advanced imaging capabilities with higher spatial resolution and faster scanning. They can map lightning, solar activity and space weather in real-time. It’s as high-tech as the weather gets!

Please note that this interview was conducted in 2019. We have recently reformatted and made minor clarity edits to publish on the Simply Neuroscience Blog!

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