The Chai laboratory is dedicated to elucidating the pathogenic mechanisms by which genetic variants contribute to undiagnosed rare and common complex neurological diseases, and to advancing genetic diagnosis, disease modeling, mechanistic studies, and precision therapeutic strategies. By integrating human genetics, iPSC-derived microglia, brain organoids, mouse and humanized disease models, CRISPR-based genetic perturbation, single-cell multi-omics, and bioinformatic analyses, the lab systematically identifies disease-causing genes and disease-risk genes, discovers diagnostic biomarkers, and dissects their underlying molecular and cellular mechanisms.

The current focus of the lab is on neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The lab aims to understand how the genetic regulatory networks and functional states of microglia influence neuroinflammatory responses, pathological progression, and neurodegeneration. Based on these mechanistic insights, the lab further develops engineered microglia and microglia replacement strategies, exploring their potential as long-lived "living medicines" that can reside within the central nervous system and provide new precision therapeutic approaches for neurological diseases.