Research areas

Our lab studies chromatin regulation in human stem cells, with a special interest in how epigenetic complexes regulate cardiac development. 

This includes understanding the molecular mechanism of epigenetic regulation by Polycomb group (PcG) and Trithorax group (TrxG) proteins, transcriptional regulation of cardiac development, DNA-binding protein in guiding epigenetic specificity, and how epitranscriptomics and epigenetics crosstalk. Interdisciplinary approaches including protein and nucleic acid biochemistry, stem cell biology, CRISPR genome editing, high-throughput genome-wide sequencing, and computational techniques are used in the lab to tackle these fundamental questions. 

Research area #1: Spatiotemporal regulation of epigenetic repression 

Polycomb group (PcG) and Trithorax group (TrxG) proteins play key roles in the epigenetic repression and activation of developmental genes. Key macromolecular interactions regulate PcG and TrxG dynamically in a spatiotemporal manner to control gene ON/OFF switch during stem cell differentiation. One of the key epigenetic complexes that we focus on is the Polycomb Repressive Complex 2 (PRC2), which catalyzes the mon-, di- and tri- methylation of Lysine 27 of histone H3 (H3K27me3, which is the hallmark for facultative heterochromatin).

Research area #2: Epigenetic regulation of cardiomyocyte differentiation and cardiovascular diseases 

Epigenetic regulation is critical for cardiovascular development and misregulation frequently leads to diseases. These epigenetic events include histone modifications, DNA methylations, higher order chromatin architecture and RNA-mediated regulations. We use iPSC - cardiomyocyte differentiation as the model system to study these processes.

hiPSC-derived cardiomyocytes

Research area #3: Regulation mechanism of RNA-binding proteins in the heart

RNA-binding proteins (RBPs) often have essential functions in biology. In the heart, RBPs play a central role in post-transcriptional or co-transcriptional regulation of gene expression. One of the highly mutated proteins in cardiovascular diseases, RBM20, is RNA-binding protein important in regulation of messenger RNA (mRNA) splicing and recognizes a consensus UCUU RNA motif through its RNA-recognition motif (RRM) domain and is almost exclusively expressed in cardiomyocytes. Mutation of RBM20 has been shown to be the drivers of to a severe dilated cardiomyopathy (DCM), in which dysregulation of alternative splicing are found in mRNA transcripts encoding key cardiomyocyte structural proteins important for contraction, like titin, or ion transport proteins, such as the CaV1.2 Ca2+ channel (CACNA1C) and the ryanodine receptor (RYR2).