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钟清

自噬和坏死在人类疾病中的作用组

电话:021-63846590-776429

邮箱:qingzhong@shsmu.edu.cn



研究方向与进展>>>

钟清实验室长期致力于哺乳动物细胞中自噬的生化机制研究。自噬是细胞分解和回收其自身物质的代谢过程。自噬对于维持细胞稳态至关重要,其功能障碍与多种疾病有关,包括癌症、神经退行性疾病和免疫疾病。钟清团队聚焦剖析自噬中的生化过程,包括脂质修饰,脂质转移,自噬膜延伸、牵引、融合,以及生物膜完整性感知、修复等。钟清团队对自噬领域做出了许多重要的贡献,其详细阐述了自噬体的形成(PNAS 2008,2010,2011),自噬底物识别(Nature 2013),及自噬体与溶酶体融合的机制(Mol Cell 2012,Nature 2015,JCB 2022)。解析自噬关键调控步骤的分子机制将为相关疾病的防治提供新思路。此外,钟清团队也关注研究新型死亡方式的生化机制和生理病理功能,以及它们与自噬的相互关系。


研究组长介绍 >>>

钟清研究员长期致力于自噬调控肿瘤细胞命运的研究。先后在美国加州大学伯克利分校和德州大学达拉斯西南医学中心任教,2017年回国后加入上海交通大学医学院,获得国家高层次人才计划、上海交通大学讲座教授等多项人才项目支持。 现任上海交通大学医学院病理生理学系主任,细胞分化与凋亡教育部重点实验室主任。通过对自噬这一细胞命运决定的关键通路的生化解析,详细阐述了自噬的生化机制和生理病理功能。总共发表高水平论文50多篇,引用超过5000多次。入选2021爱思维尔“中国高被引学者”榜单。迄今,已获得了国家自然科学基金面上和重大研究计划重点支持项目的支持,多次受邀在国际会议上做特邀报告,受邀担任国际多个学术杂志的编委,中国细胞生物学会细胞死亡研究分会会长、细胞器分会副会长,以及中美英等多个国家科学基金评审专家等。


科研项目 >>>

1. 上海教委前沿科学基地,细胞稳态和疾病,2021/08-2026/08, 2500万元,在研,主持

2. 国家自然科学基金委中德合作交流项目(Mobility programme),M-0140,Rab 及其调控蛋白在HOPS介导的自噬体-溶酶体融合中的作用及相关神经退行性疾病的研究,2021/01-2023/12,150万元,在研,主持

3. 科技部骨干项目,2019YFA0508600,线粒体和溶酶体稳态维持的蛋白质机器及其在神经退行性疾病中的作用(细胞器稳态调控的蛋白质机器在神经退变的病理及功能解析),2020/01-2024/12,249万元,在研,主持

4. 上海市2020年度“科技创新行动计划基础研究领域项目”,20JC1411100,靶向自噬的别构小分子的鉴定及其在肿瘤治疗中的应用研究,2020/10-2023/09,400万元,在研,主持

5. 国家自然科学基金重大研究计划重点支持项目,91957204,STX18介导的脂滴融合与脂滴自噬的机制与功能研究,2020/01-2023/12,330万元,在研,主持

6. 上海市科技人才计划项目,19XD1402200,自噬与肿瘤,2019/05-2022/04,40万元,结题,主持

7. 国家自然科学基金重大研究计划重点支持项目,91754205,细胞自噬体,溶酶体及内质网的相互作用及调控,2018/01-2021/12,255万元,结题,主持

8. 国家自然科学基金面上项目,31771523,营养感受激酶mTORC1对自噬特异的脂质磷酸化激酶的关键性调控机制研究,2018/01-2021/12,61万元,结题,主持


论文与专著 >>>

1. Rong, Y., Zhang, S., Nandi, N., Wu, Z., Li, L., Liu, Y., Wei Y., Zhao Y., Yuan W., Zhou C., Xiao G., Levine B., Yan N., Mou S., Deng L., Tang Z., Liu X., Kramer H., Zhong, Q. STING controls energy stress-induced autophagy and energy metabolism via STX17. Journal of Cell Biology, 2022. Jul 4;221(7). PMID: 35510944

2. Wu, Y., Jiao, H., Yue, Y., He, K., Jin, Y., Zhang, J., Zhang J., Wei Y., Luo H., Hao Z., Zhao X., Xia Q., Zhong, Q., Zhang J. Ubiquitin ligase E3 HUWE1/MULE targets transferrin receptor for degradation and suppresses ferroptosis in acute liver injury. Cell Death & Differentiation, 2022, Mar 8. PMID: 35260822.

3. Yan G……Zhong Q, Yan X. KAT-7-mediated CANX (calnexin) crotonylation regulates leucine-stimulated MTORC1 activity. Autophagy, 2022, Mar 10:1-18. PMID: 35266843.

4. Chen Q, Hao M, Wang L, Li L, Chen Y, Shao X, Tian Z, Pfuetzner RA, Zhong Q, Brunger AT, Guan JL, Diao L. Prefused lysosomes cluster on autophagosomes regulated by VAMP8. Cell Death Dis. 2021, Oct 13; 12(10):939. PMID: 34645799.

5. Klionsky……Zhong Q, Galluzzi L, Pietrocola F. Autophagy in major human diseases. EMBO J. 2021, Aug. PMID: 34459017.

6. Zheng Z……Zhong Q, Ping Li, Xiaojun Xu. Discovery of a potent SCAP degrader that ameliorates HFD-induced obesity, hyperlipidemia and insulin resistance via an autophagy-independent lysosomal pathway. Autophagy. 2021, Jul;17(7):1592-1613. PMID: 32432943.

7. Li L, Tong M, Fu Y, Chen F, Zhang S, Chen H, Ma X, Li D, Liu X, Zhong Q. Lipids and membrane-associated proteins in autophagy. Protein & Cell. 2021 Jul;12(7):520-544. PMID: 33151516.

8. Arora K, Liyanage P, Zhong Q, Naren A. A SNARE protein Syntaxin 17 captures CFTR to potentiate autophagosomal clearance under stress. FASEB J. 2021, Feb;35(2). PMID: 33191543

9. Klionsky et al., Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2021, Jan;17(4):1-382. PMID: 33634751.

10. Li P, He J, Yang Z, Ge S, Zhang H, Zhong Q, Fan X. ZNNT1 long noncoding RNA induces autophagy to inhibit tumorigenesis of uveal melanoma by regulating key autophagy gene expression MTORC1 mediated NRBF2 phosphorylation functions as a switch for PI3KC3 and autophagy. Autophagy. 2020, July;16(7):1186-1199. PMID: 31462126.

11. Galluzzi L……Zhong Q, Kroemer G. Molecular definitions of autophagy and related processes. EMBO J. 2017 Jul 3;36(13). PMID: 28596378.

12. Ma X, Zhang S, He L, Liu R, Wilz L, Sun Q, Fan W, Chen S, Yue Z, Kim J, Guan KL, Li D, Zhong Q. MTORC1 mediated NRBF2 phosphorylation functions as a switch for PI3KC3 and autophagy. Autophagy. 2017, Mar 4;13(3):592-607. PMID: 28059666.

13. Klionsky et al., Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2016, 12(1):1-222. PMID: 26799652.

14. Li L, Zhong Q. Autophagosome-lysosome fusion: PIs to the rescue. EMBO. 2016;35(17):1845-7. PMID: 27440401.

15. Wang Y, Li L, Hou C, Lai Y, Long J, Liu JK, Zhong Q, Diao J. SNARE-mediated membrane fusion in autophagy. Semin Cell Dev Biol. 2016. S1084-9521. PMID: 27422330.

16. Li X, Zhu F, Jiang J, Sun C, Zhong Q, Shen M, Wang X, Tian R, Shi C, Xu M, Peng F, Guo X, Hu J, Ye D, Wang M, Qin R. Simultaneous inhibition of the ubiquitin-proteasome system and autophagy enhances apoptosis induced by ER stress aggravators in human pancreatic cancer cells. Autophagy. 2016:1-17. PMID: 27308733.

17. Levine B, Liu R, Dong X, Zhong Q. Beclin orthologs: integrative hubs of cell signaling, membrane trafficking, and physiology. Trends Cell Biol. 2015;S0962-8924(15). PMID: 26071895.

18. Diao J, Liu R, Rong Y, Zhao M, Zhang J, Lai Y, Zhou Q, Wilz L, Li J, Vivona S, Pfuetzner R, Brunger A, Zhong Q. ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes. Nature. 2015;103(5):1244-1251. PMID: 25686604.

19. Zhi X and Zhong Q. Autophagy in Cancer. F1000Prime Rep. 2015;7:18. PMID: 25750736.

20. Zhang J, Zhong Q. Histone deacetylase inhibitors and cell death. Cell Mol Life Sci. 2014;71(20):3885-901. PMID: 24898083.

21. Tang Z, Zhu M, Zhong Q. Self-eating to remove cilia roadblock. Autophagy. 2014;10(2):379-81. PMID: 24343661.

22. Tang Z, Lin MG, Stowe TR, Chen S, Zhu M, Stearns T, Franco B, Zhong Q. Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites. Nature. 2013;502, 254-257. PMID: 24089205

23. Nazarko V and Zhong Q. ULK1 targets Beclin-1 in autophagy. Nat Cell Biol. 2013;15(7):727-8. PMID: 23817237.

24. Kim J, Kim Y, Fang C, Russell R, Kim J, Fan W, Liu R, Zhong Q, Guan KL. Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy. Cell. 2013;152(1), 290-303. PMID: 23332761.

25. Kim HJ, Zhong Q, Sheng ZH, Yoshimori T, Liang C, Jung JU. Beclin-1-interacting autophagy protein Atg14L targets the SNARE-associated protein Snapin to coordinate endocytic trafficking. J Cell Sci. 2012;125(Pt 20):4740-50. PMID: 22797916.

26. Chen D, Zhong Q. A tethering coherent protein in autophagosome maturation. Autophagy. 2012;8(6):985-6. PMID: 22617511.

27. Chen D, Fan W, Lu Y, Ding X, Chen S, Zhong Q. A mammalian autophagosome maturation mechanism mediated by TECPR1 and the Atg12-Atg5 conjugate. Mol Cell, 2012;45(5):629-41. PMID: 22342342.

28. Yan X, Sun Q, Ji J, Zhu Y, Liu Z, Zhong Q. Reconstitution of leucine-mediated autophagy via the mTORC1-Barkor pathway in vitro. Autophagy. 2012;8(2):213-21. PMID: 22258093.

29. Klionsky et al., Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2012, Apr;8(4):455-544. PMID: 22966490.

30. Hao Z, Duncan GS, Su YW, Li WY, Silvester J, Hong C, You H, Brenner D, Gorrini C, Haight J, Wakeham A, You-Ten A, McCracken S, Elia A, Li Q, Detmar J, Jurisicova A, Hobeika E, Reth M, Sheng Y, Lang PA, Ohashi PS, Zhong Q, Wang X, Mak TW. The E3 ubiquitin ligase Mule acts through the ATM-p53 axis to maintain B lymphocyte homeostasis. J Exp Med. 2012 Jan 16;209(1):173-86. PMID: 22213803.

31. Zhang J, Kan S, Huang B, Hao Z, Mak TW, Zhong Q. Mule determines the apoptotic response to HDAC inhibitors by targeted ubiquitination and destruction of HDAC2. Genes Dev 2011, Dec 15;25(24):2610-8. PMID: 22016339.

32. Lin MG, Zhong Q. Interaction between small GTPase Rab7 and PI3KC3 links autophagy and endocytosis: A new Rab7 effector protein sheds light on membrane trafficking pathways. Small GTPases. 2011 Mar;2(2):85-88. PMID: 21776407

33. Wilz L, Fan W, Zhong Q. Membrane curvature response in autophagy. Autophagy. 2011 Oct;7(10):1249-50. PMID: 21738011.

34. Fan W, Nassiri A, Zhong Q. Autophagosome targeting and membrane curvature sensing by Barkor/Atg14(L). Proc Natl Acad Sci U S A. 2011 May 10; 108(19):7769-7774. PMID: 21518905.

35. Sun Q, Zhang J, Fan W, Wong KN, Ding X, Chen S, Zhong Q. The RUN domain of Rubicon is important for hVPS34 binding, lipid kinase inhibition and autophagy suppression. J Biol Chem. 2011. Jan 7;286(1):185-91. PMID: 21062745.

36. Sun Q, Westphal W, Wong K, Tan I, Zhong Q. Rubicon controls endosome maturation as a Rab7 effector. Proc Natl Acad Sci U S A. 2010 Nov 9; 107(45):19338-43. PMID: 20974968.

37. Fan W, Tang Z, Chen D, Moughon D, Ding X, Chen S, Zhu M, Zhong Q. Keap1 facilitates p62-mediated ubiquitin aggregate clearance via autophagy. Autophagy, 2010 July 22;6(5):614-21. PMID: 20495340.

38. Sun Q, Fan W, Zhong Q. Regulation of Beclin 1 in autophagy. Autophagy. 2009 Jul 24;5(5):713-6. PMID: 19372752.

39. Sun Q, Fan W, Chen K, Ding X, Chen S, Zhong Q. Identification of Barkor as a Mammalian Autophagy-Specific Factor for Beclin 1 and Class III Phosphatidyl-inositol 3-Kinase. Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19211-6. PMID: 19050071.

40. Hall JR, Kow E, Nevis KR, Lu CK, Luce KS, Zhong Q, Cook JG. Cdc6 stability is regulated by the Huwe1 ubiquitin ligase after DNA damage. Mol Biol Cell. 2007 Sep;18(9):3340-50. PMID: 17567951

41. Ding Q, He X, Hsu JM, Xia W, Chen CT, Li LY, Lee DF, Liu JC, Zhong Q, Wang X, Hung MC. Degradation of Mcl-1 by beta-TrCP mediates glycogen synthase kinase 3-induced tumor suppression and chemosensitization. Mol Cell Biol. 2007 Jun;27(11):4006-17. PMID: 17387146.

42. Zhong Q, Gao W, Du F, Wang X. Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis. Cell. 2005, 121(7): 1085-1095. PMID: 15989957.

43. Nijhawan D, Fang M, Traer E, Zhong Q, Gao W, Du F, Wang X. Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation. Genes Dev., 2003,17(12):1475-1486.

44. Yun J, Zhong Q, Kwak JY, Lee WH. Hypersensitivity of Brca1-deficient MEF to the DNA interstrand crosslinking agent mitomycin C is associated with defect in homologous recombination repair and aberrant S-phase arrest. Oncogene. 2005 Jun 9;24(25):4009-16.

45. Zhong Q, Boyer TG, Chen P-L, and Lee W-H: Deficient nonhomologous end-joining activity in cell-free extracts from Brca1-null fibroblasts. Cancer Res. 2002, Jul 15;62 (14):3966-3970.

46. Zhong Q, Chen C-F, Chen P-L, and Lee W-H: BRCA1 facilitates microhomology-mediated end joining of DNA double strand breaks. J Biol Chem., 2002, Aug 9;277 (32):28641-28647.

47. Zhong Q, Chen C-F, Li S, Chen Y, Wang C-C, Xiao J, Chen P-L, Sharp ZD, and Lee WH:  Association of BRCA1 with the hRad50-hMre11-p95 Complex and the DNA Damage Response.  Science, 1999 Jul 30;285: 747-750. PMID: 10426999

48. Dong Z., Zhong Q, and Chen P-L:  The Nijmegen Breakage Syndrome Protein Is Essential for Mre11 Phosphorylation upon DNA Damage.  J. Biol. Chem., 1999, 274:19513-19516.

49. Zhong Q, Chen Y, Jones D, and Lee W-H:  Perturbation of TSG101 Protein Affects Cell Cycle Progression.  Cancer Res, 1998, 58: 2699-2702.

50. Zhong Q, Chen C-F, Chen Y, Chen P-L, and Lee W-H:  Identification of Cellular TSG101 Protein in Multiple Human Breast Cancer Cell Lines. Cancer Res, 1997, 57: 4225-4228.


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