Investigating the 3D epigenome in development and diseases
3D chromatin interactions between cis-regulatory elements (CREs) and genes are crucial to human health and disease. We leverage iPSC models and rare cell types isolated from the developing brain to identify cell type-specific, long-range chromatin interactions between promoters and distal CREs. These interactions have the potential to provide novel insights into genetic regulatory mechanisms during development, prioritize neuropsychiatric disease-associated SNPs, and elucidate the contribution of distal non-coding genetic variations to complex neurological disorders.

Functionally characterizing candidate cis-regulatory elements
We conduct genome-scale CRISPR screens to characterize thousands of candidate CREs  (cCREs) annotated based on biochemical signatures using iPSC models, including iPSC-derived neurons and microglia. We have developed new tools, including CRISPRpath and CRISPRview, that dramatically increase the efficiency of this process, enabling the characterization of cCREs in a cell-type-specific manner and in heterogeneous primary cells, respectively.

Linking variants to function for complex diseases 
We are integrating 3D epigenome annotations, genetic fine-mapping, and CRISPRi screening datasets of iPSC-derived neural cell types to prioritize GWAS-identified non-coding variants associated with neurological conditions, including Alzheimer’s disease and schizophrenia. Prioritized variants are functionally characterized using our newly developed PRIME, a genome-scale approach that precisely characterizes variants at base-pair resolution. Our work examines how non-coding variants contribute to cell-type-specific gene regulation and cellular functions.