Tian ChiProfessor , PhD, Professor
School of Life Science and Technology
gene function and technology
Surprisingly, although the sequences of the 20,000 mammalian protein-coding genes have been known for over 20 years, their functions in the 500 cell types remain largely enigmatic, which has constituted a key bottleneck for disease diagnosis and treatment. Convinced that technology is the mother of scientific discoveries, we have previously developed a series of genetic tools to decipher and manipulate the genome, including those for reversible gene targeting, conditional point mutation, inducible expression, and DNA and RNA base editing1-5, which has led to important scientific findings2,6-7. Our current research focuses on two areas:
1) iMAP8. This is a genetic strategy we recently reported that enables in situ disruption of 100 target genes across diverse cell types in mice. iMAP can also be used for cost-effective generation of 100 conventional single-gene KO lines via simple breeding. Simply put, iMAP accelerates gene function discovery 100-fold. We are seeking to boost iMAP throughput, and to couple iMAP to other forms of genetic perturbations including gene silencing, activation and base-editing. We are also seeking to establish an international consortium to map the “Perturb-Atlas” profiling the effects of perturbation of each of the 20,000 genes on the spatial transcriptome and epigenome throughput the body at the single-cell level in both adult mice and embryos. This atlas should become an indispensable reference map in functional genomics and a major milestone in the history of biomedical research.
2) Therapeutic targets. iMAP offers a powerful method for identifying therapeutic targets in various diseases. Our current focus is on immune-related diseases particularly cancer9. We have identified Hdac7 as a potent immune checkpoint gene in CD8 T cells whose disruption strongly enhances tumor killing by the human CAR-T cells8, and are extending the screening to other immune cells particularly NK cells.
Representative Publications (*First Author, # Corresponding Author)
- 1. Chaiyachati, Barbara H.*; Kaundal, Ravinder; Zhao, Jiugang; Wu, Jie; Flavell, Richard; Chi, Tian#.LoxP-FRT Trap (LOFT): a simple and flexible system for conventional and reversible gene targeting.BMC BIOLOGY. 2012. 10.
- 2. Jani, Anant*; Wan, Mimi; Zhang, Jianmin; Cui, Kairong; Wu, Jie; Preston-Hurlburt, Paula; Khatri, Rohini; Zhao, Keji; Chi, Tian#.A novel genetic strategy reveals unexpected roles of the Swi-Snf-like chromatin-remodeling BAF complex in thymocyte development.JOURNAL OF EXPERIMENTAL MEDICINE. 2008. 205(12):2813-2825.
- 3. Huang, Xinxin*; Lv, Junjun*; Li, Yongqin*; Mao, Shaoshuai; Li, Zhifang; Jing, Zhengyu; Sun, Yidi; Zhang, Xiaoming; Shen, Shengxi; Wang, Xinxin; Di, Minghui; Ge, Jianyang; Huang, Xingxu; Zuo, Erwei#; Chi, Tian#.Programmable C-to-U RNA editing using the human APOBEC3A deaminase.EMBO JOURNAL. 15 Oct 2020.
- 4. Liu, Yajing*; Mao, Shaoshuai*; Huang, Shisheng*; Li, Yongqin; Chen, Yuxin; Di, Minghui; Huang, Xinxin; Lv, Junjun; Wang, Xinxin; Ge, Jianyang; Shen, Shengxi; Zhang, Xiaoming; Liu, Dahai; Huang, Xingxu#; Chi, Tian#.REPAIRx, a specific yet highly efficient programmable A > I RNA base editor.EMBO JOURNAL. 15 Oct 2020.
- 5. Liu, Yajing*; Zhou, Changyang*; Huang, Shisheng*; Dang, Lu*; Wei, Yu*; He, Jun; Zhou, Yingsi; Mao, Shaoshuai; Tao, Wanyu; Zhang, Yu; Yang, Hui#; Huang, Xingxu#; Chi, Tian#.A Cas-embedding strategy for minimizing off-target effects of DNA base editors.NATURE COMMUNICATIONS. 27 Dec 2020. 11(1).
- 6. Chaiyachati, Barbara H.*; Jani, Anant; Wan, Yisong; Huang, Haichang; Flavell, Richard; Chi, Tian#.BRG1-mediated immune tolerance: facilitation of Treg activation and partial independence of chromatin remodelling.EMBO JOURNAL. 2013. 32(3):395-408.
- 7. Yongqin Li*; Yuxin Chen*; Shaoshuai Mao*; Ravinder Kaunda; Zhengyu Jing; Qin Chen; Xinxin Wang; Jing Xia; Dahai Liu; Jianlong Sun; Haopeng Wang; Tian Chi#.In situ conversion of defective Treg into SuperTreg cells to treat advanced IPEX-like disorders in mice.NATURE COMMUNICATIONS. 03 Jun 2020. 11:2781.
- 8. Liu, Bo*; Jing, Z*; Zhang, X*; Chen, Y*; Mao, S*; Yan, Z; Chi,T#*.Large-scale multiplexed mosaic CRISPR perturbation in the whole organism..CELL. Jul 2022.
- 9. Zou, Yan*; Liu, Bo*; Li, Long; Yin, Qinan; Tang, Jiaxing; Jing, Zhengyu; Huang, Xingxu; Zhu, Xuekai; Chi, Tian.IKZF3 deficiency potentiates chimeric antigen receptor T cells targeting solid tumors.CANCER LETTERS. 2022. 524:121-130.