Our research focuses on DNA topology, chromatin organization, and gene regulation in human cells (COSB, 2024). We employ both traditional assays and novel genomic and single-cell technologies developed in our lab. Notably, we developed a new assay that uses azide-trimethylpsoralen to quantitatively profile genome-wide DNA supercoiling in living cells, and reported topoisomerase-modulated supercoiling domains across the human genome that colocalize with nuclear compartments and regulate gene expression (NSMB, 2024). We are investigating the formation mechanism of DNA supercoiling domains, particularly their origins in chromatin processes, their propagation along chromatin in living cells, and their regulation by different types of DNA topoisomerases. Additionally, we study their interaction with other chromatin features, including genome organization.

Our previous work demonstrated that the dynamics of chromosomal DNA supercoiling, and its regulation by topoisomerases, is the primary driver of transcriptional bursting in bacteria (Cell, 2014). We are investigating the function of DNA supercoiling dynamics and topoisomerase activities across the human genome, particularly in chromatin regulation, gene expression, and in genome dynamic processes related to DNA damage and repair that contribute to genomic instability and aberrations. This work leverages our expertise in developing advanced genomic and single-cell technologies (Science, 2017; Genome Biology, 2023; bioRxiv, 2024). 

Our long-term goal is to elucidate the role and regulatory mechanisms of DNA supercoiling dynamics and topoisomerase activities in fundamental biological processes involving chromatin and DNA, as well as in disease contexts, including cancer chemotherapies targeting human topoisomerase.