杨崇林

 

一、研究方向：细胞器稳态调控相关机制研究

以秀丽线虫、培养细胞、小鼠等为模式，运用遗传、生化以及细胞生物学等研究方法，探索重要细胞器（线粒体、溶酶体）的稳态调控机制及其与遗传代谢性疾病之间的关系。

1.线粒体稳态与代谢

以秀丽线虫为模式，通过非偏好性的突变体筛选及基因克隆，发现调控线粒体结构、功能、融合-分裂等线粒体稳态维持的重要基因，从遗传互作、基因表达、蛋白定位和功能、线粒体结构功能、线粒体代谢等多角度开展研究，揭示线粒体稳态、代谢、及线粒体与其他细胞器互作对细胞稳态和功能的影响，揭示线粒体在遗传代谢性疾病中的作用。

       

(C. elegans mutants with abnormal mitochondria)     

(Defective lysine catabolism causes mitochondrial damage)

    

  

(Images and quantification of Mito-CMXRos staining in adult animals of N2 and slc-30A9 mutants)

(A pair of zinc transporters controls mitochondrial zinc levels)

 

2.溶酶体稳态调控机制

运用遗传学、细胞生物学、化学生物学等方法，研究溶酶体发生、溶酶体运输、溶酶体降解的调控机制，探索溶酶体稳态维持在组织器官发育中的重要作用。筛选促进溶酶体发生的小分子化合物，阐明其作用机制并研究它们在神经退行性疾病中的作用。

           

(The amino acid transporter SLC-36.1 is required for lysosome reformation from phagolysosome during apoptotic cell corpse clearance)

         

(Time-lapse monitoring of early-to-late endosome conversion in HeLa cells)

(Lysosomes receive proteins and cargos from multiple pathways)

 

二、组员

工作人员：

尹秋媛  博士，副研究员

张洁   博士，助理研究员

李婧琳  博士，助理研究员

刘楠   博士，副研究员

段梅   博士，副研究员

肖龙   博士，副研究员

罗成婷  博士，副研究员

和溢芳  博士，助理研究员

王鑫   硕士，研究实习员

李美娇  硕士，研究实习员

杨利梅  硕士，实验室管理员

马腾飞  博士后

白艳   博士后

在读研究生：

博士研究生：田飞、赵姗、杨扬、单倩、孔前进、侯成儒、陈冠宇

硕士研究生：石函冉、钱纪帆、何杉、马继仟

 

三、发表文章（2002-present）：

1. Jinglin Li, Qiuyuan Yin, Nan Xuan, Qiwen Gan, Chaolian Liu, Qian Zhang, Mei Yang, and Chonglin Yang. (2024). LYSMD proteins promote activation of Rab32-family GTPases for lysosome-related organelle biogenesis. Journal of Cell Biology doi: 10.1083/jcb.202402016.

2. Letao Li, Xilu Liu, Shanshan Yang, Meijiao Li, Yanwei Wu, Siqi Hu, Wenjuan Wang, Amin Jiang, Qianqian Zhang, Junbing Zhang, Xiaoli Ma, Junyan Hu, Qiaohong Zhao, Yubing Liu, Dong Li, Junjie Hu, Chonglin Yang, Wei Feng, Xiaochen Wang. (2024). The HEAT repeat protein HPO-27 is a lysosome fission factor. Nature 628(8008):630-638.

3. Nan Liu, Kai Liu, Chonglin Yang. (2022). WDR91 specifies the endosomal retrieval subdomain for retromer-dependent recycling. Journal of Cell Biology 221(12): e202203013.

4. Junxiang Zhou, Mei Duan, Xin Wang, Fengxia Zhang, Hejiang Zhou, Tengfei Ma, Qiuyuan Yin, Jie Zhang, Fei Tian, Guodong Wang, Chonglin Yang. (2022). A feedback loop engaging propionate catabolism intermediates controls mitochondrial morphology. Nature Cell Biology 24(4):526-537.

5. Leiling Shi, Youli Jian, Meijiao Li, Tianchao Hao, Chonglin Yang, Xiaochen Wang. (2022). Filamin FLN-2 promotes MVB biogenesis by mediating vesicle docking on the actin cytoskeleton. Journal of Cell Biology 221(7):e202201020.

6. Xiu Han, Xuning Shen, Min Wang, Xin Wang, Youli Jian, Chonglin Yang, Weixiang Guo. (2022). Loss of RNA-Binding Protein HuR Leads to Defective Ependymal Cells and Hydrocephalus. J Neurosci 42(2):202-219.

7. Ye Guo, Junjie Wu, Min Wang, Xin Wang, Youli Jian, Chonglin Yang, Weixiang Guo. (2022). The Metabolite Saccharopine Impairs Neuronal Development by Inhibiting the Neurotrophic Function of Glucose-6-Phosphate Isomerase. J Neurosci 42(13):2631-2646.

8. Tengfei Ma, Liyuan Zhao, Jie Zhang, Ruofeng Tang, Xin Wang, Nan Liu, Qian Zhang, Fengyang Wang, Meijiao Li, Qian Shan, Yang Yang, Qiuyuan Yin, Limei Yang, Qiwen Gan, and Chonglin Yang. (2021). A pair of transporters controls mitochondrial Zn²⁺ levels to maintain mitochondrial homeostasis. Protein & cell 13(3):180-202.

9. Chonglin Yang, and Xiaochen Wang. Lysosome biogenesis: Regulation and functions. (2021). Journal of Cell Biology 220(6): e202102001.

10. Ruxiao Xing, Hejiang Zhou, Youli Jian, Lingling Li, Min Wang, Nan Liu, Qiuyuan Yin, Ziqi Liang, Weixiang Guo and Chonglin Yang. (2021). The Rab7 effector WDR91 promotes autophagy-lysosome degradation in neurons by regulating lysosome fusion. Journal of Cell Biology 220 (8): e202007061.

11. Yuan Li, Xin Wang, Meijiao Li, Chonglin Yang, Xiaochen Wang. (2021). M05B5.4 (lysosomal phospholipase A2) promotes disintegration of autophagic vesicles to maintain C. elegans development. Autophagy doi: 10.1080/15548627.2021.1943178.

12. Min Wang, Changyong Tang, Ruxiao Xing, Xuezhao Liu, Xiu Han, Yinghao Liu, Lei Wang, Chonglin Yang & Weixiang Guo. (2021). WDR81 regulates adult hippocampal neurogenesis through endosomal SARA-TGFβ signaling. Molecular Psychiatry 26: 694–709.

13. Qiuyuan Yin, Youli Jian, Meng Xu, Xiahe Huang, Niya Wang, Zhifang Liu, Qian Li, Jinglin Li, Hejiang Zhou, Lin Xu, Yingchun Wang, and Chonglin Yang. (2020). CDK4/6 regulate lysosome biogenesis through TFEB/TFE3. Journal of Cell Biology 219(8):e201911036.

14. Ruofeng Tang, Xin Wang, Junxiang Zhou, Fengxia Zhang, Shan Zhao, Qiwen Gan, Liyuan Zhao, Fengyang Wang, Qian Zhang, Jie Zhang, Guodong Wang, Chonglin Yang. (2020). Defective arginine metabolism impairs mitochondrial homeostasis in Caenorhabditis elegans. Journal of Genetics and Genomics 47: 145-156.

15. Yanan Sun, Meijiao Li, Dongfeng Zhao, Xin Li, Chonglin Yang, Xiaochen Wang. (2020). Lysosome activity is modulated by multiple longevity pathways and is important for lifespan extension in C. elegans. Elife 9:e55745.

16. Rui Miao,Meijiao Li, Qianqian Zhang, Chonglin Yang, Xiaochen Wang. (2020). An ECM-to-nucleus signaling pathway activates lysosomes for C. elegans larval development. Developmental Cell 52(1): 21-37. (As a cover article)

17. Qiwen Gan, Xin Wang, Qian Zhang, Qiuyuan Yin, Youli Jian, Yubing Liu, Nan Xuan, Jinglin Li, Junxiang Zhou, Kai Liu, Yudong Jing, Xiaochen Wang, and Chonglin Yang. (2019). The amino acid transporter SLC-36.1 cooperates with PtdIns3P 5-kinase to control phagocytic lysosome reformation. Journal of Cell Biology 218 (8): 2619-2637. (As a cover article).

18. Junxiang Zhou, Xin Wang, Min Wang, Yuwei Chang, Fengxia Zhang, Zhaonan Ban, Ruofeng Tang, Qiwen Gan, Shaohuan Wu, Ye Guo, Qian Zhang, Fengyang Wang, Liyuan Zhao, Yudong Jing, Wenfeng Qian, Guodong Wang, Weixiang Guo, and Chonglin Yang. (2019). The lysine catabolite saccharopine impairs development by disrupting mitochondrial homeostasis. Journal of Cell Biology 218(2): 580-597.

(Spotlight: Saccharopine, a lysine degradation intermediate, is a mitochondrial toxin. João Leandro and Sander M. Houten. Journal of Cell Biology 218(2): 391-392).

19. Yang Li, Yu Zhang, Qiwen Gan, Meng Xu, Xiao Ding, Guihua Tang, Jingjing Liang, Kai Liu, Xuezhao Liu, Xin Wang, Lingli Guo, Zhiyang Gao, Xiaojiang Hao, Chonglin Yang. (2018). C. elegans-based screen identifies lysosome-damaging alkaloids that induce STAT3-dependent lysosomal cell death. Protein Cell 9(12): 1013–1026.

20. Caitlin Morris, Olivia K. Foster, Simran Handa, Kimberly Peloza, Laura Voss, Hannah Somhegyi, Youli Jian, My Van Vo, Marie Harp, Fiona M. Rambo, Chonglin Yang, Greg J. Hermann. (2018). Function and regulation of the Caenorhabditis elegans Rab32 family member GLO-1 in lysosome-related organelle biogenesis. PLoS Genetics 14(11): e1007772.

21. Xinli Ma, Kai Liu, Jian Li, Huanhuan Li, Jun Li, Yingfang Liu, Chonglin Yang and Huanhuan Liang. (2018). A non-canonical GTPase interaction enables ORP1L-Rab7-RILP complex formation and late endosome positioning. Journal of Biological Chemistry 293(36): 14155-14164.

22. Kai Liu, Ruxiao Xing, Youli Jian, Zhiya ng Gao, Xinli Ma, Xiaojuan Sun, Yang Li, Meng Xu, Xin Wang, Yudong Jing, Weixiang Guo and Chonglin Yang. (2017). WDR91 is a Rab7 effector required for neuronal development. Journal of Cell Biology 216(10): 3307-3321.

(Spotlight: A new Rab7 effector controls phosphoinositide conversion in endosome maturation. Casanova J. and Winckler B. Journal of Cell Biology 216(10): 2995-2997).

23. Jianhua Yin, Yaling Huang, Pengfei Guo, Siqi Hu, Sawako Yoshina, Nan Xuan, Qiwen Gan, Shohei Mitani, Chonglin Yang, Xiaochen Wang. (2017). GOP-1 promotes apoptotic cell degradation by activating the small GTPase Rab2 in C. elegans. Journal of Cell Biology 216(6): 1775-1794.

24. Xuezhao Liu, Yang Li, Xin Wang, Ruxiao Xing, Kai Liu, Qiwen Gan, Changyong Tang, Zhiyang Gao, Youli Jian, Shouqing Luo, Weixiang Guo, and Chonglin Yang. (2017). The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote aggrephagy. Journal of Cell Biology 216(5): 1301-1320.

(JCB 2018 Special Collection on Mitochondria and Autophagy).

25. Chonglin Yang, Xiaochen Wang. (2017). Cell Biology in China: Focusing on the Lysosome. Traffic 18(6): 348-357.

26. Shiya Cheng, Kai Liu, Chonglin Yang, Xiaochen Wang. (2017). Dissecting Phagocytic Removal of Apoptotic Cells in Caenorhabditis elegans. In Methods in Molecular Biology: Phagocytosis and Phagosomes (Eds. Roberto Botelho) Springer New York 1519: 265-284.

27. Yuan Li, Baohui Chen, Wei Zou, Xin Wang, Yanwei Wu, Dongfeng Zhao, Yanan Sun, Yubing Liu, Lianwan Chen, Long Miao, Chonglin Yang, Xiaochen Wang. (2016). The lysosomal membrane protein SCAV-3 maintains lysosome integrity and adult longevity. Journal of Cell Biology 215(2): 167-185.

28. Yang Li, Meng Xu, Xiao Ding, Chen Yan, Zhiqin Song, Lianwan Chen, Xiahe Huang, XinWang, Youli Jian, Guihua Tang, Changyong Tang, Yingtong Di, Shuzhen Mu, Xuezhao Liu, Kai Liu, Ting Li,Yingchun Wang, Long Miao, Weixiang Guo, Xiaojiang Hao and Chonglin Yang. (2016). Protein kinase C controls lysosome biogenesis independently of mTORC1. Nature Cell Biology 18: 1065-1077.

(研究亮点News and Views: Turn up the lysosome. Paul Saftig, Albert Haas. Nature Cell Biology 18: 1025-1027).  

29. Xiaochen Wang, Chonglin Yang. (2016). Programmed cell death and clearance of cell corpses in Caenorhabditis elegans. Cellular and Molecular Life Sciences 73: 2221-2236.

30. Kai Liu, Youli Jian, Xiaojuan Sun, Chengkui Yang, Zhiyang Gao, Zhili Zhang, Xuezhao Liu, Yang Li, Jing Xu, Yudong Jing, Shohei Mitani, Sudan He, Chonglin Yang. (2016). Negative regulation of phosphatidylinositol 3-phosphate levels in early-to-late endosome conversion. Journal of Cell Biology 212(2): 181-198.

(研究亮点In Focus: Making sure late endosomes are on time. Mitch Leslie. Journal of Cell Biology 212: 127).

31. Meng Xu, Yubing Liu, Liyuan Zhao, Qiwen Gan, Xiaochen Wang, and Chonglin Yang. (2014). The lysosomal cathepsin protease CPL-1 plays a leading role in phagosomal degradation of apoptotic cells in Caenorhabditis elegans. Molecular Biology of the Cell 25: 2071-2083.

32. Didi Chen, Youli Jian, Xuezhao Liu, Yuanya Zhang, Jingjing Liang, Xiaying Qi, Hongwei Du, Wei Zou, Lianwan Chen, Yongping Chai, Guangshuo Ou, Long Miao, Yingchun Wang, Chonglin Yang. (2013). Clathrin and AP2 are required for phagocytic receptor-mediated apoptotic cell clearance in Caenorhabditis elegans. PLoS Genetics 9(5): e1003517.

33. Jing Xu, Xiaojuan Sun, Yudong Jing, Mo Wang, Kai Liu, Youli Jian, Mei Yang, Zhukuan Cheng, Chonglin Yang. (2012). MRG-1 is required for genomic integrity in Caenorhabditis elegans germ cells. Cell Research 22, 886-902.

34. Didi Chen, Hui Xiao, Kai Zhang, Bin Wang,Zhiyang Gao, Youli Jian, Xiaying Qi, Jianwei Sun, Long Miao, Chonglin Yang. (2010). Retromer is required for apoptotic cell clearance by phagocytic receptor recycling. Science 327(5970): 1261-1264.

(Editor's Choice: Corpse-sorting machinery. S. M. Hurtley. Science Signaling 2010, 3, ec73; Highlighted by Nature China).

35. Xiao Yang and Chonglin Yang. (2010). An everlasting role of animal models in understanding human disease. Journal of Genetics and Genomics 37(9): 557.

36. Youli Jian, Zhiyang Gao, Jianwei Sun, Qinfang Shen, Feng Feng, Yudong Jing and Chonglin Yang. (2009). RNA aptamers interfering with nucleophosmin oligomerization induce apoptosis in cancer cells. Oncogene 28(47): 4201-4211.

37. Qinfang Shen, Fengsong Qin, Zhiyang Gao, Jie Cui, Hui Xiao, Zhiheng Xu, and Chonglin Yang. (2009). Adenine Nucleotide Translocator Cooperates with Core Cell Death Machinery to Promote Apoptosis in Caenorhabditis elegans. Molecular and Cellular Biology 29(14): 3881–3893.

38. Mei Yang, Jianwei Sun, Xiaojuan Sun, Qinfang Shen, Zhiyang Gao, Chonglin Yang. (2009). Caenorhabditis elegans Protein Arginine Methyltransferase PRMT-5 Negatively Regulates DNA Damage-Induced Apoptosis. PLoS Genetics 5(6): e1000514.

39. Hui Xiao, Didi Chen, Zhou Fang, Xiaojuan Sun, Jing Xu, Song Song, Jiajia Liu and Chonglin Yang. (2009). Lysosome biogenesis mediated by vps-18 affects apoptotic cell degradation in Caenorhabditis elegans. Molecular Biology of the Cell 20(1): 21-32.

40. Chonglin Yang, Myoung Sook Kim, Devulapalli Chakravarty, Fred E. Indig and France Carrier. (2009). Nucleolin Binds to the Proliferating Cell Nuclear Antigen and Inhibits Nucleotide Excision Repair. Molecular and Cellular Pharmacology 1(3):130-137.

41. Xiaochen Wang, Jin Wang, Keiko Gengyo-Ando, Lichuan Gu, Chun-Ling Sun, Chonglin Yang, Yong Shi, Tetsuo Kobayashi, Yigong Shi, Shohei Mitani, Xiaosong Xie and Ding Xue. (2007). C. elegans mitochondrial factor WAH-1 promotes phosphatidylserine externalization in apoptotic cells through phospholipid scramblase SCRM-1. Nature Cell Biology 9(5): 541-549.

42. Chonglin Yang, Nieng Yan, Jay Parish, Xiaochen Wang, Yigong Shi and Ding Xue. (2006). RNA aptamers targeting the cell death inhibitor CED-9 induce cell killing in C. elegans. Journal of Biological Chemistry 281(14): 9137-9144.

43. Jay Z Parrish, Chonglin Yang, Binghui Shen, Ding Xue. (2003). CRN-1, a Caenorhabditis elegans FEN-1 homologue, cooperates with CPS-6/EndoG to promote apoptotic DNA degradation. EMBO Journal 22(13): 3451-60.

44. Xiaochen Wang, Chonglin Yang, Jijie Chai, Yigong Shi, Ding Xue. (2002). Mechanisms of AIF-mediated apoptotic DNA degradation in Caenorhabditis elegans. Science 298(5598):1587-92.