Our research is focused on the interface between DNA topology, chromatin organization and gene regulation in human cells. Our approaches include traditional assays, as well as genomic technologies and single-cell assays newly invented in the lab. Previously we have shown that the dynamics of chromosomal DNA supercoiling tension and its balanced regulation by two types of topoisomerases is the primary mechanism underlying the phenomenon of transcriptional bursting in bacteria (Cell, 2014). We aim to probe DNA supercoiling dynamics in human cells during a variety of key biological processes. A particular goal is to understand the role and regulation of DNA topology in the context of chromatin architecture, transcriptional activity, and other epigenetic features.

Previously we have developed a single-cell whole-genome amplification method, Linear Amplification via Transposon Insertion (LIANTI), that enables the accurate detection of single-cell genomic variants, including copy-number variations (CNVs), single-nucleotide variations (SNVs), and structural variations (SVs) (Science, 2017). We aim to further develop single-cell sequencing assays that can help us better understand chromatin biology in a dynamic manner within heterogenous cell populations. We will also bring these new single-cell techniques to both fundamental questions in biology and clinical settings in medicine via collaborative efforts.