Neurobiology of neurological disorders
Despite a recent flood of research identifying genome-wide association (GWAS) loci in a range of neurological disorders, many of the loci reside in intronic/intergenic regions of the genome, making it difficult to understand the neurobiological mechanisms of the disorder. Our goal is to leverage multiple functional genomics toolkits to assign GWAS loci to their target genes, and provide rich insights into the neurological basis of neurological 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.
3D structure of genome in human disease
We try to implement Hi-C and Micro-C, genome-wide chromosome conformation capture techniques to identify the three-dimensional structure in the disease context. Our work shows how knowledge of chromatin contacts facilitates large scale annotation of non-coding elements in the genome and how disease-relevant cellular contexts shape gene regulatory architecture.