|1987 B.Medicine, Fudan University Medical School, China
1996 Ph.D in Biological Chemistry, UCLA, USA
1996-2003 Postdoc,Stanford University, USA
2003-2015 Assistant Professor, Associate Professor, Research Scientist, Yale University, USA.
2015-present Professor, ShanghaiTech University, China
2016-present Adjunct Professor, Dept Immunobiology, Yale University, USA.
|（1）Transgenerational epigenetic inheritance. Environmental stimuli such as diet, toxins, stress and emotions can induce persistent changes in gene activity without mutating DNA, and surprisingly, such changes can sometimes be propagated to the offspring. Thus, our traits are determined not only by our genes, but also the life experiences and even the emotions of our ancestors (http://tv.greenmedinfo.com/the-ghost-in-your-genes-epigenetics/). This amazing phenomenon is turning classic genetics on its head, but its molecular basis is complex. We have established the simplest mouse model to attack this problem10,11.
（2）Mouse genetic tools. Convinced that technology is the mother of scientific discoveries, we have developed multiple mouse genetic tools3,7,8,9, with the current focus being high-throughput screening. For the majority of genes, we only know their sequences but not the functions. High-throughput screening is a powerful approach for unveiling gene functions, but it can only be performed in vitro, which severely restricts its applications and constitutes a major bottleneck in genetics, as most of the biological processes can not be (readily) recapitulated in vitro. We are taking a novel molecular genetic strategy (that combines Cre with Cas9) to break this bottleneck, and will eventually use our method to uncover the functions of genes(especially LncRNA genes)in live mice.
1. T. Chi, A BAF-centred view of the immune system, Nat. Rev. Immunol. 4, 965–977 (2004).
2. M. Yu, M. Wan, J. Zhang, J. Wu, R. Khatri, T. Chi, Nucleoprotein structure of the CD4 locus: implications for the mechanisms underlying CD4 regulation during T cell development, Proc. Natl. Acad. Sci. U.S.A. 105, 3873–3878 (2008).
3. A. Jani, M. Wan, J. Zhang, K. Cui, J. Wu, P. Preston-Hurlburt, R. Khatri, K. Zhao, T. Chi, A novel genetic strategy reveals unexpected roles of the Swi-Snf-like chromatin-remodeling BAF complex in thymocyte development, J. Exp. Med. 205, 2813–2825 (2008).
4. D. Lai, M. Wan, J. Wu, P. Preston-Hurlburt, R. Kushwah, T. Grundström, A. N. Imbalzano, T. Chi, Induction of TLR4-target genes entails calcium/calmodulin-dependent regulation of chromatin remodeling, Proc. Natl. Acad. Sci. U.S.A. 106, 1169–1174 (2009).
5. M. Wan, J. Zhang, D. Lai, A. Jani, P. Prestone-Hurlburt, L. Zhao, A. Ramachandran, G. R. Schnitzler, T. Chi, Molecular basis of CD4 repression by the Swi/Snf-like BAF chromatin remodeling complex, Eur. J. Immunol. 39, 580–588 (2009).
6. J. Wang, H. Gu, H. Lin*, T. Chi*, Essential roles of the chromatin remodeling factor BRG1 in spermatogenesis in mice, Biol. Reprod. 86, 186 (2012). *co-corresponding author
7. B. H. Chaiyachati, R. Kaundal, J. Zhao, J. Wu, R. Flavell, T. Chi, LoxP-FRT Trap (LOFT): a simple and flexible system for conventional and reversible gene targeting, BMC Biol. 10, 96 (2013).
8. B. H. Chaiyachati, A. Jani, Y. Wan, H. Huang, R. Flavell, T. Chi, BRG1-mediated immune tolerance: facilitation of Treg activation and partial independence of chromatin remodelling, Embo J. 32, 395-408 (2013).
9. M. Wan, R. Kaundal, H. Huang, J. Zhao, X. Yang, B. H. Chaiyachati, S. Li, T. Chi, A general approach for controlling transcription and probing epigenetic mechanisms: application to the CD4 locus, J Immunol 190, 737–747 (2013).
10. M. Wan, H. Gu, J. Wang, H. Huang, J. Zhao, R. K. Kaundal, M. Yu, R. Kushwaha, B. H. Chaiyachati, E. Deerhake, T. Chi, Inducible mouse models illuminate parameters influencing epigenetic inheritance, Development 140, 843–852 (2013).
11. S. Mao, Y. Li, B. Liu, T. Chi. Mouse models of epigenetic inheritance: Classification, mechanisms and experimental strategies. In “Handbook of Epigenetics, Second Edition” (Elsevier). Edited by T. Tollefsbol (in press).