On the phone one day during her first year at UC Berkeley, Choi asked her mom what she’d think about her studying accounting.
“There was no answer on the other side,” recalled Choi, now the Samuel A. Goldblith Career Development Assistant Professor of Applied Biology. ”So I said, ‘Ok, maybe not’.”
Choi initially gravitated to science and math because her family had immigrated to Southern California from South Korea when she was a teenager and the language barrier was less of a problem in those classes. Throughout high school and college she found she had a knack for biology, so she continued on to graduate school at Caltech. There she found a mentor in Professor David Anderson, a prominent biologist who was beginning to take an intensive interest in brain. She became one of the first students in his lab to tackle research in the central nervous system.
Above: Choi with an image from her 2016 paper in Science, showing abnormal cortical development (on right) resulting from in utero exposure to the cytokine IL-17a. Photo credit: Justin Knight.
Her thesis research, published in Neuron in 2005, identified a molecular pathway the brain employs in circuits between the amygdala and hypothalamus to mediate between conflicting primal behaviors such as mating and defending oneself from predators.
A leap of faith across the country
At Caltech, she could go home every week to see her parents and grandmother (and to bring her laundry). Taking her next step, she said, was therefore very difficult: moving from Pasadena to a postdoctoral fellowship at Columbia University. But it was no ordinary opportunity to work in the lab of Professor Richard Axel, who in 2004 shared the Nobel Prize with Linda Buck for key discoveries of the structure of the olfactory system.
Axel urged Choi to model the big picture of what she was trying to study – to hypothesize not just one step of a process but to formulate a potential explanation of a whole phenomenon. In Axel’s lab she studied the processes that link the input of a smell to the output of a behavior through learning.
When she joined the MIT faculty Brain and Cognitive Sciences faculty in 2013, she did so in part because she felt the environment would push her to blaze her own trail.
“I’m not an adventurous person,” Choi said. “I felt like this could be a place where I will be naturally pushed to test my limits because this is a place of innovation.”
A blossoming field yields autism insights
The new trail led to “neuroimmunology.” Her lab studies the interaction of the immune system with the brain and the effects of that interaction on neurodevelopment, behavior and mood. She is particularly interested in how cytokines, proteins that immune cells use to communicate, may act as neuromodulators that influence the development and activity of neurons in the cortex.
In the same spirit she learned in Axel’s lab, she has embarked on a collaboration that has richly modeled the process by which maternal infection can lead to aberrant neurodevelopment. In this research, she works side-by-side with her husband Jun Huh, an immunologist across the Charles at Harvard Medical School.
In a 2016 paper in Science, their team showed in a mouse model of maternal immune activation (MIA) that the link between MIA and the development of autism-like behavioral abnormalities in offspring was a particular type of maternal immune system T-cell and its secretion of the cytokine IL-17a, which reaches the brain of the fetus. The collaboration followed with two papers in Nature in September 2017. One showed the phenomenon required the presence of maternal intestinal bacteria that promote the differentiation of the T cell. The other showed that excessive IL-17a in the brain during development leads to a deficit of neural inhibition specifically in the S1DZ region of the cortex. The team showed that by intervening to reduce excess activity there, they could mitigate behavioral abnormalities associated with maternal infection.
Motivated by those findings, Choi’s long-term translational goal is to develop ways to assess the risk of maternal infection leading to neurodevelopmental disorders, prevent the development of disease, and mitigate it post-development. Also, because her research has identified the S1DZ region, which is hypothesized to be important for proprioception, or the brain’s sense of where the body is in space, she is also studying the connection between that and social behavior.
“As we gather more data about the interaction of these two systems, we realize it’s such an important interaction to look at,” she said. “It’s not just us. The field of neuroimmunology is blossoming.”
So is Choi’s career choice of science.