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.
Human brain evolution
Human evolution is hypothesized to be driven primarily by changes in gene regulation rather than divergence in protein-coding sequences. Recent comparative genomic and epigenomic studies have identified non-protein coding regions on the human lineage having either accelerated sequence or epigenetic changes. We seek to bridge the gap between genetic changes on the human lineage and molecular basis of human evolution by mapping these genomic elements onto their putative target genes using chromatin architecture in human brain.