Ukpong Eyo, PhD, is a UVA Health researcher looking into the action of the brain's own immune cells, microglia.
As the leader of his own lab at UVA Health's Center for Brain Immunology and Glia (BIG), his research focuses on understanding microglial activity in neurodevelopment and neurodevelopmental pathologies. Through this research, he hopes to identify how microglia regulate normal brain development and determine their reactivity and contributions during abnormal brain development, acute injury, or disease.
See Eyo's research interests and selected publications, and below, Eyo discusses his work and gives his answers to our Researcher Highlight questions:
What are you working on right now?
Our lab is interested broadly in the role of microglia in the developing, mature, and diseased brain, and we tackle questions in three specific arms of research. We're fascinated by these cells because they make up a small population of cells in the brain (~10%) but are constantly active in the brain.
- One arm of research in the lab is focused on examining the contributions of microglia in seizure disorders, including in an animal model of a human developmental seizure condition called Dravet syndrome.
- A second arm is centered on elucidating the features of microglial regulation and modulation of the structure and function of the brain vasculature.
- A third is targeted toward elucidating microglial interactions with other cell types in the brain. In each of these arms, we're interested in features of development, maturity, and various diseases, including how they affect the different sexes.
What are the most intriguing potential clinical applications of your work?
One of the exciting potential clinical applications of our work is our research on microglial-vascular interactions in the context of neurodegenerative Alzheimer’s disease (AD). In AD, two features are receiving a lot of attention from both the clinical and scientific literature:
- Vascular dysfunction happens early and chronically in the disease
- Microglial dysfunction persists in the condition
What has been poorly interrogated is the possibility that microglial dysfunction may precipitate vascular dysfunction in AD. Our recent work suggested that microglia may regulate blood vessel structure and function.
Whether and how this is disrupted in AD is not known, but we believe that our findings have potential implications to improve AD outcomes by targeting features of vascular dysfunction through ameliorating microglial dysfunction. We're excited by this prospect and have a lot of fundamental science work to do to test this possibility.
What recent discovery/paper/presentation has impacted the way you think?
There are a lot of exciting papers coming out. But one that really intrigues me is from the Holtzman Lab at Washington University in St. Louis that was published this year in Nature.
Speaking of the interaction between the nervous and immune systems, this study showed that in AD, T cells, which are immune cells that do not normally reside in the brain, infiltrate the brain in response to certain disease hallmarks. This infiltration was observed in both human tissue and mouse models of the disease. Interestingly, these T cells were shown to promote neurodegeneration in concert with microglia.
What is exciting about this research is that it suggests that immunotherapies targeting the peripheral (outside the brain) immune system as well as the central (the brain’s) immune system could be a beneficial approach to treating AD.
What made you choose UVA Health as the place to do your research?
During my postdoctoral training, it became clear that UVA Health was one of the foremost research centers interested in examining the interface between the immune and nervous systems, especially within the context of neurodevelopmental and neurodegenerative diseases.
Because I was already interested in doing research on microglia, the brain’s resident immune cell, but had not studied them with robust immunological training, this environment, and especially the researchers at UVA’s Brain Immunology and Glia (BIG) Center, was extremely desirable as a place for me to build my research career.
What do you wish more people knew about your area of research?
I wish more people knew about the promise microglia can hold for neurological disease. They are a first-line defense in the brain and serve as your brain's innate immune cells and, therefore, are very important for brain function.
Moreover, because they are not originally born in the brain, they have unique receptors that we can target in disease to potentially help alleviate brain pathologies. This is a very exciting prospect.
How did you become interested in your area of research?
My journey to my research field had to do with mentors who guided me appropriately. In graduate school, the leader of a lab, Dr. Michael Dailey, selected me to join his lab to study microglia at a time I did not know much about the brain or had ever heard of the term “microglia.” He developed my abilities to become interested in microglial research in development.
I then pursued postdoctoral training with Dr. Long-Jun Wu, who was also extremely passionate about neuroscience broadly, but microglia in disease specifically. He also helped to extend and cement my interest in this field.
Finally, as a leader of my own lab at UVA Health, I derive much inspiration from my fellow colleagues here who are doing incredible work all around, as well as the diverse members of my lab doing the research and coming up with very exciting results.