Psychedelic medicine has long been used as part of the ritual and therapeutic alternative to traditional medicine. Especially, psilocybin and MDMA have shown promise as a treatment contributing to the psychological recovery in patients with PTSD and resistant depressive disorders. However, very few studies have explored the molecular basis behind the therapeutic effects. This project particularly aims to understand neuronal and glial mechanisms behind the psychedelic therapeutic effects using functional imaging and cell-based assays.

Psychedelics are a class of psychoactive substance that produces changes in perception, cognition, and moods. Psychedelics are also a target of serotonergic receptors that are known to regulate various physiological functions ranging from mood behaviors to brain plasticity. This particular project aims to understand how psychedelics modulate the plastic measures of the brain cells and how this modulation can potentially benefit the disease states and recovery process using mice models that mimic phenotypes of various neuropsychiatric disorders including substance use and co-morbid 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).