Research

Generally, eukaryotic genomes and nuclei are divided into two large compartments known as euchromatin, which contains most protein-coding genes, and heterochromatin, which mainly contains simple and complex repeated DNAs. Proper targeting of sequences into each compartment is necessary for genome stability and gene regulation. We study regulation of structural heterochromatic proteins and their effect on nuclear, cellular and physiological phenotypes.

We apply advanced biophysical, biochemical, and imaging approaches in silico, in vitro, and in vivo to understand how physical phenomena like liquid-liquid phase separation guide the organization of chromatin in the nucleus. Our goals are to understand how complex, dynamic condensates containing DNA/nucleosome polymers and multivalent proteins are established in early development, how they are propagated through replication and division, and how they impact in vivo genome and nuclear functions.

Repeated DNAs enriched in heterochromatin pose significant challenges to DNA replication and genome stability. For example, homologous recombination (HR) involving double-strand breaks (DSBs) in repetitive sequences generates chromosome aberrations that cause cell death and contribute to cancer progression. We develop precisely controlled systems to study how the cell avoids catastrophe when its repetitive DNA is aberrantly replicated or damaged.