Stanley Qi lab @ Stanford Bioengineering
Genetic Engineering | Synthetic Biology | Cell Design and Therapy
The Stanley Qi laboratory is interested in developing new bioengineering technologies with a focus on discovery-based synthetic biology for biomedical applications. We study how the mammalian genome regulate itself for achieving complex cellular functions, and how to rationally design and re-engineer the genome and genetic circuits for therapeutics.
For technology development, we developed the first nuclease-deactivated Cas9 (dCas9) for sequence-specific gene regulation in bacteria, yeast, and mammalian cells. Based on the dCas9 platform, we demonstrated the CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) technologies as switches to activate or repress genes in the genome. We co-developed CRISPR imaging that allows dynamic tracking of desired genomic loci in living cells. We developed CRISPR-GO (Genome Organization), a versatile method that enables 3-Dimensional (3D) manipulation of the genome structure and its nuclear architecture. We developed CRISPR-IO (Input/Output) methods that couple cell surface receptors (GPCRs) to CRISPR to engineer mammalian cells that can sense environmental signals and regulate desired genome programs. These methods expands our capability to control, perturb, and manipulate the genome from small scale (cis-regulatory elements) to large scale (genetic circuitry and 3D genome), useful for studying genomics and engineering synthetic cells.
For discovery-based synthetic biology, we adopted principles and techniques in the synthetic biology for biological- or biomedical-relevant discoveries. We are understanding the principles of molecular design and circuitry design in mammalian cells, including how T cell receptors detect antigen and perform tumor-killing functions, how stem cells coordinate environmental cues and genetic cues to maintain or change cell fates, how dynamic circuits can be implemented to create sensor-actuator systems. By engineering at the interface from molecular to cellular to organismal levels, we hope to make bioengineering as a discover approach to reveal novel biology.