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?