Wei QiAssociate Professor , PhD, Associate Professor
School of Life Science and Technology
- 1995/09-2001/06, Nanjing University , BS, MS
- 2003/05-2006/12, Southwestern Medical Center at Dallas, UT, PhD
- 2007/09-2008/09, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Research Associate Professor
- 2008/09-2018/03, Novartis Institutes of BioMedical Research, Investigator, Senior Investigator, AD
Epigenetics and Translational Research
Histone modification is a major epigenetic factor modifying gene transcription on top of inherited genetic information. It regulates cellular status such as proliferation and differentiation and designates the identity of specific cells. The machinery for histone modification is composed of writers (enzymes adding the modification to histones), erasers (enzymes removing the modification) and readers (proteins recognizing the modification and transduce signals). Mutation or dysfunction of these epigenetic machineries has been implicated in multiple diseases such as cancer, autoimmune diseases and metabolic diseases.
My lab is focusing on dissecting the epigenetic characteristics of the disease and validating their pathophysiological functions using integrated approaches of epigenetics, chemical biology and gene editing. The goal of our work is to identify effective targets and potential lead compounds for therapeutic development, so that the patients will benefit.
（1）PRC2（Polycomb Repressive Complex 2）is composed of core components EZH1/2, Suz12 and EED. It is the sole enzyme resposible for histone H3K27 methylation, which often associates with gene repression. Genetic alterations of EZH2/Suz12/EED has been found in multiple cancers and validated as driving events. PRC2 inhibitors targeting to the enzymatic subunit EZH1/2 or the allosteric subunit EED have been discovered and brought into anti-cancer clinical studies.
(2）Adipose tissue plays important roles in animals.White adipose tissue (WAT) stores energy in lipids, while brown fat (BAT) is responsible for nonshivering thermogenesis through UCP1-1 mediated energy dissipation. Although epigenetic mechanisms modulate differentiation in multiple lineages, the epigenetic regulation of brown adipocyte differentiation is poorly understood. By screening a collection of epigenetic compounds, we found that Lysine-Specific Demethylase 1 (LSD1) inhibitors repress brown adipocyte differentiation. RNAi-mediated Lsd1 knockdown causes a similar effect, which can be rescued by expression of wild-type but not catalytic-inactive LSD1. Mechanistically, LSD1 promotes brown adipogenesis by demethylating H3K4 on promoter regions of Wnt signaling components and repressing the Wnt pathway. Furthermore, deletion of Lsd1 in mice leads to inhibition of brown adipogenesis, validating the pivotal role of LSD1 in brown fat development in vivo.
In addition, we identified Gpnmb as a liver-secreted factor regulating lipogenesis in WAT. In humans, Gpnmb is tightly associated with body mass index and is a strong risk factor for obesity. Gpnmb inhibition by a neutralizing antibody or liver-specific knockdown improves metabolic parameters, including weight gain reduction and increased insulin sensitivity, probably by promoting the beiging of WAT. Gpnmb inhibition may provide a therapeutic strategy in obesity and diabetes.
Representative Publications (*First Author, # Corresponding Author)
- 1. Chu, Liping*; Qu, Yuxiu; An, Yang; Hou, Linjun; Li, Juewan; Li, Weijia; Fan, Gaofeng; Song, Bao-Liang; Li, En; Zhang, Liye; Qi, Wei#.Induction of senescence-associated secretory phenotype underlies the therapeutic efficacy of PRC2 inhibition in cancer.CELL DEATH & DISEASE. 15 Feb 2022. 13(2).
- 2. Jiang, Shi-You*; Yang, Xinglin; Yang, Zimo; Li, Jue-Wan; Xu, Meng-Qiang; Qu, Yu-Xiu; Tang, Jing-Jie; Li, Yun-Feng; Wang, Liguo; Shao, Yi-Wen; Meng, Xin-Yuan; Hu, Huili; Song, Bao-Liang#; Rao, Yu#; Qi, Wei#.Discovery of an insulin-induced gene binding compound that ameliorates nonalcoholic steatohepatitis by inhibiting sterol regulatory element-binding protein-mediated lipogenesis.HEPATOLOGY. 01 Apr 2022.
- 3. Zhao, Jiaqi*; Zhou, Ailin; Qi, Wei#.The Potential to Fight Obesity with Adipogenesis Modulating Compounds.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 01 Feb 2022. 23(4).
- 4. Hui Qian*; Zhao JQ(赵佳琦)*; Xinyi Yang; Sujuan Wu; Yang An; Yuxiu Qu; Zhen Li; Hui Ge; En Li; Wei Qi#.TET1 promotes RXRα expression and adipogenesis through DNA demethylation.BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS. Apr 2021. 1866(6).
- 5. Zhou, Zhang-Sen*; Li, Mei-Xin; Liu, Jie; Jiao, Hengwu; Xia, Jing-Ming; Shi, Xiong-Jie; Zhao, Huabin; Chu, Liping; Liu, Jingrong; Qi, Wei; Luo, Jie; Song, Bao-Liang#.Competitive oxidation and ubiquitylation on the evolutionarily conserved cysteine confer tissue-specific stabilization of Insig-2.NATURE COMMUNICATIONS. 17 Jan 2020. 11(1).
- 6. Gong, Xue-Min*; Li, Yun-Feng*; Luo, Jie*; Wang, Ji-Qiu*; Wei, Jian*; Wang, Ju-Qiong; Xiao, Ting; Xie, Chang; Hong, Jie; Ning, Guang; Shi, Xiong-Jie; Li, Bo-Liang; Qi, Wei#; Song, Bao-Liang#.Gpnmb secreted from liver promotes lipogenesis in white adipose tissue and aggravates obesity and insulin resistance.NATURE METABOLISM. May 2019. 1(5):570-583.
- 7. Qi, Wei*; Zhao, Kehao*; Gu, Justin*; Huang, Ying*; Wang, Youzhen; Zhang, Hailong; Zhang, Man; Zhang, Jeff; Yu, Zhengtian; Li, Ling; Teng, Lin; Chuai, Shannon; Zhang, Chao; Zhao, Mengxi; Chan, Homan; Chen, Zijun; Fang, Douglas; Fei, Qi; Feng, Leying; Feng, Lijian; Gao, Yuan; Ge, Hui; Ge, Xinjian; Li, Guobin; Lingel, Andreas; Lin, Ying; Liu, Yueqin; Luo, Fangjun; Shi, Minlong; Wang, Long; Wang, Zhaofu; Yu, Yanyan; Zeng, Jue; Zeng, Chenhui; Zhang, Lijun; Zhang, Qiong; Zhou, Shaolian; Oyang, Counde; Atadja, Peter; Li, En#.An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED.NATURE CHEMICAL BIOLOGY. 2017. 13(4):3810.
- 8. Chen, Yan*; Kim, Jeesun; Zhang, Ruipeng; Yang, Xiaoqin; Zhang, Yong; Fang, Jianwu; Chen, Zhui; Teng, Lin; Chen, Xiaowei; Ge, Hui; Atadja, Peter; Li, En; Chen, Taiping; Qi, Wei#.Histone Demethylase LSD1 Promotes Adipocyte Differentiation through Repressing Wnt Signaling.CELL CHEMICAL BIOLOGY. 2016. 23(10):1228-1240.
- 9. Qi, Wei*; Chan, HoMan*; Teng, Lin; Li, Ling; Chuai, Shannon; Zhang, Ruipeng; Zeng, Jue; Li, Min; Fan, Hong; Lin, Ying; Gu, Justin; Ardayfio, Ophelia; Zhang, Ji-Hu; Yan, Xiaoxia; Fang, Jialuo; Mi, Yuan; Zhang, Man; Zhou, Tao; Feng, Grace; Chen, Zijun; Li, Guobin; Yang, Teddy; Zhao, Kehao; Liu, Xianghui; Yu, Zhengtian; Lu, Chris X.; Atadja, Peter; Li, En#.Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2012. 109(52):21360-21365.
- 10. Jiang, Shi-You*; Tang, Jing-Jie; Xiao, Xu; Qi, Wei; Wu, Suqian; Jiang, Chao; Hong, Jiaxu; Xu, Jianjiang#; Song, Bao-Liang#; Luo, Jie#.Schnyder corneal dystrophy-associated UBIAD1 mutations cause corneal cholesterol accumulation by stabilizing HMG-CoA reductase.PLOS GENETICS. Jul 2019. 15(7).
- 11. Jiang, Shi-You*; Li, Hui; Tang, Jing-Jie; Wang, Jie; Luo, Jie; Liu, Bing; Wang, Jin-Kai; Shi, Xiong-Jie; Cui, Hai-Wei; Tang, Jie; Yang, Fan; Qi, Wei; Qiu, Wen-Wei#; Song, Bao-Liang#.Discovery of a potent HMG-CoA reductase degrader that eliminates statin-induced reductase accumulation and lowers cholesterol.NATURE COMMUNICATIONS. 03 Dec 2018. 9.