Research Interest

The main research focus of our group is on structural studies of gene expression and regulation. Two themes of investigation include epigenetic control of gene transcription and mRNA processing:

1. Epigenetic control gene expression

Epigenetic phenomena are stable inheritance of gene expression patterns controlled by higher order chromatin structure that depends on covalent modifications of DNA and histones. Epigenetic control of gene expression plays important roles in many biological processes, such as in cell type specifications during development, as well as in the development of many environment and age related diseases, such as cancer and diabetes. Our research in this area includes structural and functional studies of the catalytic mechanisms of histone modification enzymes, their substrate specificity, the mechanisms by which the enzymatic activities are regulated, the structural basis for the recognition of modified histones, and the mechanism of establishment and maintenance of higher chromatin structure in general. The results of our study will provide important mechanistic insights into the function of epigenetic inheritance in cell differentiation, epigenetic reprogramming in somatic cloning and iPS techniques, epigenetic deregulation in cancer and aging, and the development of therapeutics targeting epigenetic regulators.

2. RNA processing and protein-RNA interaction

Post-transcriptional mRNA processing includes 5'-capping, splicing and poly-adenylation at the 3' end. Our current research focuses on mRNA splicing, as most human genes are alternatively spliced, which results in multiple proteins from a single transcript, thus, greatly increased the complexity of the human proteome. RNA splicing is carried out by the spliceosome, which is a large, dynamic complex composed of more than a hundred proteins and several small nuclear RNAs. Our goal is to elucidate the structural basis for splice sites selection and the molecular mechanism of RNA splicing, which include protein-protein and protein-RNA interaction within the spliceosome, and the interaction between the spliceosome, splicing factors and mRNA. In addition, mRNA splicing is coupled to transcriptional regulation, and our interest also includes structural and functional studies of protein-protein and protein-RNA interactions coupling the two processes