Research Interests

Along with genetic factors, environmental factors are critical contributors to inflammatory and neurodevelopmental disorders. Gut microbes serve as one of these non-genetic factors that define a threshold to either maintaining a homeostatic balance or developing diseases. For example, pre- and postnatal exposure to microbiota in our body has been suggested to correlate with the development of various inflammatory diseases, such as asthma, allergies, atopy, diabetes, and inflammatory bowel disease (IBD).

Recently we showed that maternal immune activation (MIA) during pregnancy alters maternal microbiota and primes T cells in their offspring (Kim and Paik et al., 2022 Immunity). We will further investigate how changes in maternal gut microbiota educate offspring T cells and affect their neurological phenotypes. 

One of the major characteristics of neurodevelopmental disorders, such as autism spectrum disorder (ASD), is a sex bias: males have a two to four times higher risk of developing ASD than females. Although efforts have been made to identify the underlying causes of these differences, what drives the sex bias is still unclear.
Recently, by using a rodent model, we have shown that maternal immune activation (MIA)-induced autism-like behavioral abnormalities are present only in male but not in female offspring, and it is due to activation of the integrated stress response (ISR) pathway is manifested in male, but not female, brains of developing embryos (Kalish and Kim et al., 2020, Nat. Neurosci.).
We further hypothesize that dysfunction in the placenta exposed to maternal adversity during pregnancy contributes to the male-specific manifestations of neurodevelopmental defects. Successful completion of this study will lay the foundation for future studies to identify novel therapeutic strategies for neurodevelopmental disorders.

Traditionally, the CNS has been appreciated as an immune-privileged site. However, the paradigm is shifting these days: complex neuro-immune and neuro-gut interactions occur in pathological and homeostatic conditions. However, a deeper level of understanding of how these three systems communicate and orchestrate in neuropathophysiology is still lacking.
To broaden our understanding and discover novel approaches for developing therapeutics, we will take a reductionist approach to uncover bi-directional interaction among three systems. We will focus on homeostatic/physiological level regulation as well as various neurological disorders, not only neurodevelopmental but neurodegenerative disorders.