Q&A: How Microglia Could Change Medicine

July 6, 2021 By Caroline Challe, cfc8ev@virginia.edu Caroline Challe, cfc8ev@virginia.edu

Ukpong Eyo knew that he wanted to come to the University of Virginia well before he arrived in Charlottesville, because he admired the work of neuroscientist Jonathan Kipnis, formerly the director of UVA’s Center for Brain Immunology and Glia.

Kipnis led the team behind a stunning 2016 discovery of previously unknown vessels connecting the brain and the immune system. Since then, UVA has continued to blaze new trails in neuroscience, and Eyo – who came to the U.S. from Nigeria as an undergraduate and joined the University in 2018 – is now a big part of that work. He heads the Eyo Lab in the Center for Brain Immunology and Glia, studying microglia (a type of cells in the central nervous system) and their effect on behavioral or developmental disorders, as well as neurodegenerative diseases like Alzheimer’s.

His work has important implications for how we treat behavioral or developmental disorders. We caught up with him to learn more.  

Q. You received your undergraduate degree in zoology. Can you explain how that prepared you for the rest of your career in research and why you chose that path?

A. I don’t know that I chose the path as opposed to the path chose me. I’m originally from Nigeria, and I applied to come to the States for school and I was accepted to Northwest Missouri State University.

Once I got there, I knew I wanted to go to med school, and their main program to prepare you for med school was this pre-professional zoology. 

Northwest Missouri State University was a smaller institution, and my advisers were very welcoming and took a very special personal interest in me. They got me excited about what research could look like. Even though I wanted to go to med school, meetings with some of my faculty members pushed me toward research. 

Q. Why did Jonathan Kipnis’ research at UVA interest you?

A. Jonathan Kipnis came out with a study that showed that by manipulating microglia cells, we could actually improve the phenotype [observed symptoms] of a newer developmental disorder called Rett syndrome [a genetic disorder that results in loss of coordination and speech]. The study made a big splash, and for the first time, I kept thinking about how we could use microglia to treat various diseases. That got me very excited, and so from that day, I decided to pursue a career in studying microglia cells. 

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Jonathan Kipnis headshot
Eyo said he was inspired by the work of BIG Center founder Dr. Jonathan Kipnis, and sought a position at UVA as a result. (Photo by Dan Addison, University Communications)

I got to meet Jonathan Kipnis in 2014, and it was a fantastic experience; he was very down to earth. He was at UVA, so I dreamt about getting a faculty position there. I kept in touch with him, and then he started the Brain Immunology and Glia center and made another huge discovery in 2015. In 2018, I was lucky enough to secure a position here at UVA.

Q. Can you explain microglia and their function? 

A. Yes, yes. The brain is made up of cells called neurons. However, half of brain cells are other cells called “glia.” Microglia originate in the embryo outside the brain and make their way to the brain, and so we think they can be manipulated independent of cells that originate in the brain itself.

Dysfunctional microglia can be problematic in different pathologies. We know that one of the biggest problems of Alzheimer’s disease is that the microglia do not function correctly. So one of the big ideas is how we can replace dysfunctional microglia with healthy microglia.

Q. Can you explain how your research with microglia and behavior are linked?

A. We focus on a certain gene that’s really important in microglia, and what we found out is that if you take out this gene in males and females, you get different behaviors. 

So normally, mice are social creatures; they like to spend time with other mice. But if you take out this gene in mice, you now start seeing that the male mice are not as social anymore. If you take it out in females, it doesn’t matter, they’re still social at the same level, but they’re more anxious. 

So, we’re seeing this one protein and this one receptor that may be regulating differently in males versus females, and we still do not understand the underlying basis for that. But that’s why we will continue to have a job.

Q. Are there other examples of the importance of microglia?

A. A few years ago, a study came out that says that the microglia play an important role in obesity. Other studies show that they also affect neurodevelopmental disorders like autism or Alzheimer’s disease. It feels like you can go anywhere and microglia are important in various brain diseases. So presumably, some of the therapies in the future would be targeted toward alleviating or improving microglial function so that it can improve brain function.

Q. Can you describe how you and your team work together on this research?

A. I’m proud of the lab we put together, and intentional about it, because we are a pretty diverse lab on many fronts. We have people who were born and raised on four different continents. All of us have diverse backgrounds and different aspects of training. We really celebrate that and come together to tackle this question of microglia.

So that’s one aspect of our diversity, but there’s another aspect that we like to celebrate – the different stages of our career development. I am the head of the lab, and then we have five post-docs, two graduate students, a lab technician, and a handful of undergrads. We often highlight how collaborative we are, and we all help each other on our different projects. A paper that’s going to be published, hopefully soon, credits eight-plus people from the lab because everybody pitched in to help out with different projects.

So, we work very collaboratively, and it goes beyond the lab itself to outside our research. On Memorial Day, we had a social get-together, and recently, we celebrated our undergrads by going bowling. 

The Brain, Immunology and Glia center, which is where our lab is located, is also a fantastic environment. Everything that I’ve told you about the way my lab works can be extended beyond to the center. It has emerged as a center of amazing research, which is also very collaborative, and has wonderful trainees.

Q. What’s next for your research? 

A. Oh, man. I don’t have enough time to share all the details but it is sufficient to say that beginning August 1st of this year (which marks my third year of starting my lab here at UVA), our lab will be funded by two 5-year grants from the National Institutes of Health. One of these grants is focused on studying microglia as a target of febrile seizures. The first grant is focused on studying microglial interactions with blood vessels in the brain. This is important because these vessels deliver nutrients and oxygen to the brain, and this is impaired in various disease conditions such as in Alzheimer’s disease.

We are investigating if microglia can regulate blood delivery to the brain, which may have implications for the treatment of various brain diseases and injuries.

These grants are a pretty surreal opportunity and I have an amazing team that has brought us this far and is eager to accomplish the work in a center that has a worldwide reputation for great caliber research. Stay tuned!