3D structure of genome in human brain
We try to implement Hi-C, a genome-wide chromosome conformation capture technique to identify the three-dimensional structure in human brain. Our work shows how knowledge of chromatin contacts facilitates large scale annotation of non-coding elements in the genome, including common variants associated with neuropsychiatric illnesses and non-coding regulatory elements related to human brain evolution.
Genetic basis of psychiatric disorders
Despite a recent flood of research identifying genome-wide association (GWAS) loci in a range of psychiatric disorders, many of the loci reside in intronic/intergenic regions of the genome, making it difficult to understand the neurobiological mechanisms of the disorder. These non-coding variants are often located in the regulatory regions and exert their effects through long-range regulation of gene expression. Our goal is to leverage multiple functional genomics data including Hi-C and QTLs to assign GWAS loci to their target genes, and provide rich insights into the genetic basis of psychiatric disorders.
Multiplexed reporter assays
To functionally characterize non-coding variants associated with human traits and diseases, we employ a massively parallel reporter assay (MPRA), a high-throughput screening platform that enables the simultaneous functional validation of regulatory activity of thousands of variants in a single experiment. We plan to apply MPRA to hundreds of thousands of genetic variants associated with a wide range of diseases to (1) decode the principle underlying variant effects on gene regulation and (2) prioritize variants causally implicated in diseases.