Decoding Noncoding RNA's Functional Elements
RNA is typically understood as an intermediary molecule between DNA and protein. But, some noncoding RNAs, as well as the noncoding regions of messenger RNA, have been well appreciated as important regulators of gene expression and cellular functions. As increasing numbers of noncoding RNAs are implicated in development and diseases, the forefront of current RNA research centers on understanding its regulatory roles beyond coding potential. We develop and apply high-throughput functional genomics platforms that allow systematic, quantitative dissection of noncoding RNAs' sequence and structure. By integrating these assays with computational modeling, we aim to uncover the functional codes embedded in noncoding RNAs and understand how noncoding RNAs influence gene expression programs. A recent project includes the development of massively parallel RNA assay combined with immunoprecipitation (MPRNA-IP).
Recruitment Mechanisms of Chromatin Regulators in Brain Disorders
Another major research direction centers on the epigenetic regulation of gene expression. We focus on the mechanisms that dynamically recruit chromatin regulators (for example, Polycomb complexes and Trithorax complexes) to specific genomic loci. By dissecting how transcription factors, cofactors, and cis-regulatory elements guide the chromatin complexes to specific loci, we aim to understand chromatin state and transcriptional outputs determining cell identities. This work also seeks to uncover how disruptions in recruitment dynamics contribute to epigenetic dysregulation and risk for brain disorders. A recent project includes the RNA-mediated regulation of LSD1/KDM1A recruitment and its implication in psychiatric disorders.
Genetic Regulation of Gene Expression Programs
In parallel, we investigate the genetic regulation of gene expression programs, focusing on how sequence variation and cis-regulatory elements influence the interactions among DNA, RNA and proteins. A recent project includes genetic regulation of miRNA in human brain tissues.