Research Interests:
Cell growth is coordinated with the availability of nutrients, which is determined by intracellular nutrient sensors. Deregulation in nutrient sensing have implications for human diseases, such as cancer and diabetes. We have long-standing interest in understanding how various kinds of nutrients are sensed, especially the sensing of amino acids. We are also interested in other types of nutrients or metabolites, such as fatty acids, vitamins, minerals and gut microbial metabolites. We combine tools of molecular biology, biochemistry, cell biology, genetics, bioinformatics and chemical biology to study molecular mechanisms, and meanwhile we use model organisms C. elegans and mice to investigate physiopathology. Below are some topics regarding nutrient sensing and concept extensions:
1) Amino-acid/Fatty-acid sensing and cell growth control
2) The role of minerals and vitamins in cell growth control
3) How gut microbial metabolites regulate host physiology
4) Identification of intracellular targets of important drugs
Scientific Contributions:
We have nutrients from daily meals, including amino acids, glucose, fatty acids and others. Cell metabolism and growth are coordinated with the supply of nutrients. We have focused on the nutrient amino acids, investigating how cells sense amino-acid levels to modulate cell growth. Our most important discovery is a leucine sensor protein called SAR1B, which senses cytosolic leucine concentrations and regulates cell growth by controlling mTORC1 activity. Importantly, the leucine sensor SAR1B is frequently mutated in human lung cancers; in mouse models, SAR1B deficiency remarkably promoted lung cancer development through activating mTORC1. Taken together, this finding is both theoretically and practically significant.
Honors and Awards
2020 The Ray Wu Prize
2018 ‘Best Ten Student Researchers’ of Peking University (including Science and Arts)
2018 National Scholarship
Selected Articles(*equal contributors,#corresponding authors)
Yiwei Xu*, Jie Chen*, Jianguo Chen, Junlin Teng. EI24 promotes cell adaption to ER stress by coordinating IRE1 signaling and calcium homeostasis. EMBO Rep. 2022, 23(3):e51679.
Jie Chen*#, Yuhui Ou*, Rong Luo, Jie Wang, Dong Wang, Jialiang Guan, Yi Li, Peixue Xia, Peng R. Chen, Ying Liu#. SAR1B senses leucine levels to regulate mTORC1 signalling. Nature. 2021, 596(7871):281-284.
Jie Chen, Yuhui Ou, Yanyan Yang, Wen Li, Yuntao Xie, Ying Liu. KLHL22 activates amino-acid-dependent mTORC1 signaling to promote tumorigenesis and ageing. Nature. 2018, 557(7706):585-589.
Jie Chen*, Yuhui Ou*, Yi Li, Shumei Hu, Li-Wa Shao, Ying Liu. Metformin extends C. elegans lifespan through lysosomal pathway. eLife. 2017, 6:e31268.