The Park lab integrates stem cell biology and innovative technologies to advance understanding of human brain development and its related disorders.
1. Construction and deconstruction of human cortex:
We develop methods to generate human brain organoids that recapitulate the developing human brain. Specifically, forebrain is a major target region. During embryogenesis, telencephalon and diencephalon give rise to rostral and caudal forebrain. Using a combination of growth factors, and changing the treatment timing, we construct the brain organoids representing distinct subdomains of cortex. By performing scRNA-seq, immunostaining, and electrophysiological approach, we characterize them. With the brain organoids in hand, we investigate the function of genes known for neurodevelopmental disorders.
2. Epigenetic regulation of human pluripotent stem cells:
Human pluripotent stem cells (hPSCs) are capable of undergoing unlimited self-renewal and differentiating into any cell types. However, long-term culture of hPSCs results in the undesirable epigenetic changes. Particularly, X chromosomes in female hPSCs display unpredictable behaviors, limiting their use in disease modeling and cellular therapeutics. Using advanced genomics tools (ChIP-seq, HiC, ATAC-seq, and scRNA-seq), we aim to define the X chromosome status in female hPSCs and to devise methods to stabilize them.