The Qi Lab is broadly interested in three topics:
1. Develop technologies for efficient and high-throughput genome engineering in mammalian cells.
We are interested in developing new tools that enable easy and flexible human genome engineering and endogenous gene regulation. In particular, we focus on repurposing bacterial Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system for controlling gene expression using Watson-Crick basepairing RNAs. So far, we have develop the following technologies:
1) CRISPR interference (CRISPRi) - a programmable RNA-guided transcriptional silencing technology in bacteria, yeast, and mammlian cells
2) Modular ways for endogenous gene activation and repression in mammalian cells
3) Live imaging in mammlian cells using CRISPR for visualizing chromatin state and dynamics
We are now focusing on technologies that enable targeted epigenetic regulation of the human genome, e.g. modifying histone or DNA marks. We also apply whole-genome high-throughput genome perturbation for functional profiling.
2. High-throughput profiling of gene function and regulatory elements during cell differentiation
We apply genome-wide technologies to understand gene function and regulatory roles of DNA elements during cell differentiation. Understanding how multiple genes and regulatory elements coordinate with other is key to elucidate genetic programs for complex phenotypes. In particular, we are interested in interrogating mutual interaction between transcription factors and epigenetic regulators during cell development using both high-throughput genomic technologies and computational modeling.
3. Design complex genetic systems for directing cell reprogramming
Previous methods of cell reprogramming required overexpression of a few exogenous genes. In contrast, endogenous genomic programs form complex networks to sense cellular state, and perform dynamic regulation. Recapitulating the natural regulatory programs, we are interested in creating complex gene circuits to detect signals and make decisions for directing cell differentiation.