1. Why did you become interested in biological sciences?
My interest in biological sciences started when I was a child. Growing up I was very sickly, so I would frequently go in and out of the hospital. I had 3 major hospitalizations, one of which I underwent surgery to remove a tumor pressing on my cerebellum and part of my occipital lobe. Since I was always in the hospital, I grew up under the care of a lot of doctors. I was always amazed at how they know so much about the human body and how, with this knowledge, they can impact the lives of people in need by providing them with medical care and treatment. Since then, I wanted to study human physiology and disease progression all the way to a molecular level, and hopefully with my future work as a researcher I will also be able to help other people.
2. Please introduce a biological phenomenon that has attracted your attention.
For quite some time now I would frequently revel at the brain’s complexity. We may not realize it on a day-to-day basis, but once we look at how neurological disorders affect an individual we get to see how (beautifully!) intricate the brain’s machinery actually is. One neurological disorder in particular has recently caught my attention: anti-NMDA receptor encephalitis. I first read of this disease through the book Brain on Fire by Susannah Cahalan. NMDA receptors, ionotropic channels that open in response to glutamate release, are widespread in the brain and have been shown to play an important role in synaptic plasticity and memory formation. In this type of encephalitis, antibodies against NMDA receptors are produced by the body’s own immune system. When they cross the blood-brain barrier, they impair the function of NMDA receptors, leading to symptoms characteristic of psychiatric disorders such as hallucinations, behavioral changes, impaired consciousness, and seizures. Motor disturbances and autonomic dysfunction are also common symptoms of anti-NMDA receptor encephalitis*. This disease has caught my attention for a few reasons: (1) it gives a picture as to how the nervous and immune systems affect each other, (2) it gives a biological basis for symptoms characteristic of psychiatric disorders (what if patients sent to mental institutions can actually be treated in the hospital?), and (3) it makes us appreciate just how important our brain is in our daily lives.
* Barry, H., Byrne, S., Barrett, E., Murphy, K. C., & Cotter, D. R. (2015). Anti-N-methyl-d-aspartate receptor encephalitis: Review of clinical presentation, diagnosis and treatment. BJPsych Bulletin,39(1), 19-23.
3. Please tell us your hypothesis that can be used to explain the biological phenomenon mentioned.
Recent studies have already identified mechanisms by which the immune system produce these autoantibodies and how they cause damage at neuronal synapses. One thing that is not yet fully understood, however, is how these antibodies penetrate the blood-brain barrier (BBB).
The clinical profiles of patients with anti-NMDA receptor encephalitis show that they either had a history of teratomas or viral diseases. My hypothesis is that these conditions affect the balance of signaling molecules that regulate BBB permeability. Examples of such molecules are cytokines or eicosanoids, and they are responsible for regulating CNS inflammation in the brain to restore homeostasis. However, teratomas or viral diseases may prolong this inflammation and damage the BBB wall, thus allowing anti-NMDA receptor antibodies to pass through.
4. In what experimental ways do you think you can prove your hypothesis?
One way of analyzing BBB permeability in human patients is by checking protein concentrations in the CSF. Transport of proteins such as albumin and IgGs are normally blocked by the BBB. To further study BBB permeability in vivo, mouse models for teratoma or viral infections can be used. We can check for changes in the concentrations of signaling molecules associated with BBB permeability (such as cytokines) through immunohistochemistry and study their mechanism of action by using specific drug inhibitors or agonists.
5. Please tell us the most memorable episodes you had in the department of biological sciences (or in KAIST).
Taking Professor David Helfman’s courses was definitely memorable. In his last year here at KAIST, I was able to take two of his classes—Cell Biology Experiment Laboratory and Landmark Discoveries in Cell Biology. Prior to the laboratory class I did not have a lot of experiences working on biological research thus the experiments we performed were difficult for me at first. However, with patience and a lot of Prof. Helfman’s encouragement, I gained the confidence and the skill to work with wet experiments. The Landmark Discoveries class, on the other hand, taught me the ‘logic’ of a biologist—how to ask good questions, how to formulate a hypothesis, and how to choose the appropriate experimental methods to prove this hypothesis. Together, these two classes provided me with insight on how I can prepare myself for a career in research.
6. Any other story you want to share?
When I was younger I never imagined that I would be
flying to Korea on my own and study here for high school and college. As I
mentioned earlier, I was often sick, and adding to that I was a shy person and
extremely dependent on others. What I have learned over the years, however, is
that you should not allow these weaknesses to dictate the dreams or goals you
set for yourself. Acknowledge that these weaknesses are part of your beautiful
story, allow yourself time to grow, and dream high :)