Psychedelic compounds have long been used in ritual practices and as therapeutic alternatives to traditional medicine. These compounds primarily target serotonergic receptors, which regulate a wide range of physiological processes, including mood, cognition, and brain plasticity. While the role of 5-HT receptor signaling in neuronal plasticity has been extensively studied, much less is known about how these signaling pathways influence glial cells and their interactions with neurons. Many subtypes of 5-HT receptors belong to the family of G protein-coupled receptors (GPCRs), which mediate diverse downstream signaling cascades and cellular responses. This project aims to elucidate the cellular and molecular mechanisms underlying serotonergic receptor activation in both neuronal and glial populations using functional imaging and human cell-based assays. By uncovering how receptor-mediated signaling shapes neuron–glial communication, we seek to better understand the fundamental processes governing brain function and dysfunction and to identify novel therapeutic targets for neurological and psychiatric disorders.

Of two distinct pathways (i.e. G protein and β-arrestin pathways), studies in the field have mainly focused on G protein pathways in drug discovery. My thesis research in Dr. Richard van Rijn's lab at Purdue investigated the role of the β-arrestin-mediated pathway in emotional behaviors, aiming to further elucidate the mechanisms behind the non-canonical pathways in psychiatric behaviors. My research discovered that β-arrestin pathways, not G protein pathways, provide therapeutic effects towards anxiety- and fear-related behaviors in mice through unique downstream signaling. This was the first study that showed a differential role of the two β-arrestin isoforms in mood behaviors and in unique brain regions, and it was published in Science Signaling (Ko et al., 2021) and highlighted as a cover art.

As a part of the collaborative research award project that was funded by the Purdue Institute of Integrative Neuroscience, I and Dr. Logan Ganzen in Dr. Yuk-Fai Leung's lab investigated pain-like behavior mediated by TRPA1 calcium channels using high-throughput assays with zebrafish larvae. This research established a high-throughput assay to identify novel anti-pain medications using the zebrafish larvae and provides a system to investigate the role of β-arrestin in mediating TRPA1 channel signaling. This unique project highlighting the TRPA1-mediated behaviors in multi-modal systems including zebrafish, mice and cells was published in Scientific Reports (Ko and Ganzen et al., 2019).