Modeling neurodevelopmental disorders using iPSC-derived neurons and brain organoids.

We aim to study the pathophysiological mechanisms underlying ASD phenotype using patient‐specific human induced pluripotent stem cell (hiPSC)‐derived cortical neurons and brain organoids with focus on calcium signaling and synaptic transmission. Human iPSC-derived neurons recapitulate the genomic, molecular and cellular attributes of native human neuronal subtypes with advantages over single time point studies.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social communication deficits and frequent comorbidities such as epilepsy. Genetic studies indicate that ASD-associated risk variants converge on calcium signaling pathways and vesicle fusion.

Using human iPSC-derived cortical neurons and 3D cortical organoids, as well as zebrafish models, we study store-operated Ca²⁺ entry (SOCE) in neuronal hyperactivity. We employ functional assays such as single-cell calcium imaging, whole-cell patch-clamp electrophysiology, and microelectrode array (MEA) recordings to characterize pathophysiological changes.

Extracellular vesicle (EV) biomarkers and EV-mediated inflammation in neurological disorders.

Exosomes and EVs can be good for biomarker discovery for different types of diseases. Exosomes are small vesicles (40–100 nm in diameter) and are thought to be the carriers of signaling macromolecules and RNAs for cell-to-cell communication. The goal of this project is to identify and validate a list of EV biomarkers for early diagnosis of ASD.

These markers could facilitate the development of clinical targets for early intervention to prevent, delay or reduce the severity of ASD.

Lipid dysregulation in neurological diseases.

Lipid metabolism plays a crucial role in maintaining neuronal function, and alterations in lipid composition, including the reduction of phosphatidylinositol 4,5-bisphosphate (PIP2), have been implicated in neurodegenerative disorders. PIP2 is a key regulator of cell signaling and membrane trafficking, and its dysregulation is associated with neuronal dysfunction. Our research was the first to demonstrate that PIP2 functions as an electrostatic catalyst for vesicle fusion by lowering the hydration energy barrier (ACS Nano, 2024; Science Advances, 2025). We propose a paradigm shift in which PIP2 is recognized as a lipid catalyst for vesicle fusion, expanding our understanding of the molecular mechanisms governing neurotransmitter release.

Additionally, our findings indicate that cholesterol is essential for Ca²⁺-dependent vesicle fusion by enhancing membrane bending and deformation (Advanced Science, 2023).

Our research aims to identify potential therapeutic interventions by targeting lipid dysregulation and modulating protein-lipid interactions.

RIBOMONE in physiology and pathology.

My group first reported the active exocytosis of miRNAs independently of exosomes in response to neuronal stimulation.

We propose a new function of non-coding RNAs named (‘ribomone’ = ribonucleotide + hormone), and suggest that miRNAs may function as hormones; i.e., miRNA is stored in vesicles and released by vesicle fusion in response to stimulation, thereby contributing to cell-to-cell communication.

We study the role of ribomone in physiology and pathology.