We work on technology development for genome engineering, discovery-focused synthetic biology, and epigenetic gene therapy. We aim to develop new technologies for studying the mammalian genome and treating complex diseases.
For technology development, we are interested in novel technologies that reprogram the mammalian genome and epigenome. We developed the first nuclease-dead dCas9 from the natural CRISPR-Cas9 nuclease. We developed a series of CRISPR tools that greatly enriched the CRISPR toolbox and expanded genome engineering beyond editing. These tools include CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) for targeted gene activation and repression, LiveFISH for live imaging of DNA and RNA, CRISPR-GO for manipulating the 3D genome organization, and miniature Cas (CasMINI) and hyper-efficient Cas12a (hyperCas12a) for in vivo applications. We harness natural molecules for molecular engineering and evolve novel functions. These tools are broadly used by the community for research and and translational applications.
For discovery-focused synthetic biology, we apply synthetic biology to design and engineer molecules and molecular circuits in mammalian cells. We use synthetic systems to study how cells can be rationally designed as an 'engineering' entity and be harnesses for disease treatment. For example, we engineer T cells to detect new antigens to kill cancer cells or stem cells to integrate environment cues to determine cell fate. By engineering at the scale from molecular to cellular to organismal level, we hope to make synthetic biology a better discovery tool.
For epigenetic gene therapy, we combine epigenome engineering, synthetic biology, and disease models to develop novel therapy to treat cancer, neurodegeneration, and complex genetic diseases. We aim to reveal the importance of noncoding elements including enhancers in the regulation of genome and disease. We harness safe and powerful tools to precisely rewrite the epigenome marks to reverse or cure diseases. We developed PAC-MAN as a treatment to influenza and broad variants of SARS-CoV-2. We aim to greatly expand genome and epigenome engineering towards neurodegenerative diseases and complex diseases.