Since completion of the Human Genome Project (HGP), advances in DNA sequencing technologies have propelled the growth of genome sequencing from one individual (10^0) to hundreds of thousands (>10^5). If this exponential pace continues, the genomes of all humans (<10^10) would be sequenced within the next 20 years. In each personal genome there are thousands of rare genetic variants for which the impacts upon gene function, and disease risk, are unclear. These variants of uncertain significance (VUS) comprise the vast majority of clinical variants and severely hamper the utility of genetic information in precision medicine.

Our team tackles the challenge of VUS interpretation through establishing and applying state-of-the-art high throughput functional assays to comprehensively measure variant effects. These technologies such as deep mutational scanning (DMS) and saturation genome editing (SGE) combine saturation mutagenesis, cell-based functional characterization, and massively parallel sequencing, to measure the functional consequence of thousands of variants in one experiment, with precise resolution for each individual variant. We also seek to innovate by integrating high-throughput functional assays with single cell sequencing and genome editing technologies to  improve variant interpretation in the clinic and advance our understanding of variant effect in basic research.