Research

Due to limited availability of patient-derived tumor samples, animal-based models have been widely used to study molecular mechanisms of tumor progression. However, the animal models do not adequately reproduce the pathology of human brain diseases from molecular and genetical standpoints. Recently, brain organoids or spheroids have been developed from human pluripotent stem cells or cancer cell lines in three-dimensional culture system. The organoids mimics in vivo brain microenvironment, and offer invaluable applications for the disease modeling and the drug testing. We are using the organoid/spheroid system to explore the pathogenetic mechanism and the drug response of human brain tumor.

Recent advance of genomic sequencing technologies enables us to profile gene expression level at single-cell resolution and has been applied to various patient-derive brain samples, brain organoids, and other cancer models. In our laboratory, we are analyzing in-house and public single-cell RNA-seq or ATAC-seq of brain samples and brain organoids to understand how gene expression and chromatin structure are changed throughout disease progression.

Cancer cells display stem cell-like properties, such as undifferentiated state and immortal growth, and share several molecular programs with embryonic stem cells. Throughout extensive analysis of RNA-seq data, we previously identified a novel splicing isoform of Cyclin E1 gene (pCCNE1) that is uniquely expressed in human embryonic stem cells, but not in normal somatic cells. Interestingly, pCCNE1 is also highly expressed in cancer, but its functional roles in cancer progression is largely unknown. In our lab, we are investigating the relationship of pCCNE1 with cancer phenotypes.