基本信息 >>>
研究方向與進(jìn)展>>>
鐘清實(shí)驗(yàn)室長(zhǎng)期致力于哺乳動(dòng)物細(xì)胞中自噬的生化機(jī)制研究,。自噬是細(xì)胞分解和回收其自身物質(zhì)的代謝過(guò)程,。自噬對(duì)于維持細(xì)胞穩(wěn)態(tài)至關(guān)重要,，其功能障礙與多種疾病有關(guān),，包括癌癥,、神經(jīng)退行性疾病和免疫疾病,。鐘清團(tuán)隊(duì)聚焦剖析自噬中的生化過(guò)程，包括脂質(zhì)修飾,，脂質(zhì)轉(zhuǎn)移,，自噬膜延伸、牽引,、融合,，以及生物膜完整性感知、修復(fù)等,。鐘清團(tuán)隊(duì)對(duì)自噬領(lǐng)域做出了許多重要的貢獻(xiàn),，其詳細(xì)闡述了自噬體的形成（PNAS 2008,，2010,，2011），自噬底物識(shí)別（Nature 2013）,，及自噬體與溶酶體融合的機(jī)制（Mol Cell 2012,，Nature 2015，JCB 2022）,。解析自噬關(guān)鍵調(diào)控步驟的分子機(jī)制將為相關(guān)疾病的防治提供新思路,。此外，鐘清團(tuán)隊(duì)也關(guān)注研究新型死亡方式的生化機(jī)制和生理病理功能,，以及它們與自噬的相互關(guān)系,。
|
研究組長(zhǎng)介紹 >>>
鐘清研究員長(zhǎng)期致力于自噬調(diào)控腫瘤細(xì)胞命運(yùn)的研究。先后在美國(guó)加州大學(xué)伯克利分校和德州大學(xué)達(dá)拉斯西南醫(yī)學(xué)中心任教,，2017年回國(guó)后加入上海交通大學(xué)醫(yī)學(xué)院,，獲得國(guó)家高層次人才計(jì)劃、上海交通大學(xué)講座教授等多項(xiàng)人才項(xiàng)目支持,。 現(xiàn)任上海交通大學(xué)醫(yī)學(xué)院病理生理學(xué)系主任,，細(xì)胞分化與凋亡教育部重點(diǎn)實(shí)驗(yàn)室主任。通過(guò)對(duì)自噬這一細(xì)胞命運(yùn)決定的關(guān)鍵通路的生化解析,，詳細(xì)闡述了自噬的生化機(jī)制和生理病理功能,。總共發(fā)表高水平論文50多篇，引用超過(guò)5000多次,。入選2021,、2022愛(ài)思維爾“中國(guó)高被引學(xué)者”榜單。迄今,，已獲得了國(guó)家自然科學(xué)基金面上和重大研究計(jì)劃重點(diǎn)支持項(xiàng)目的支持,，多次受邀在國(guó)際會(huì)議上做特邀報(bào)告，受邀擔(dān)任國(guó)際多個(gè)學(xué)術(shù)雜志的編委,，中國(guó)細(xì)胞生物學(xué)會(huì)細(xì)胞死亡研究分會(huì)會(huì)長(zhǎng),、細(xì)胞器分會(huì)副會(huì)長(zhǎng)，以及中美英等多個(gè)國(guó)家科學(xué)基金評(píng)審專家等,。 |
科研項(xiàng)目 >>>
1. 國(guó)家自然科學(xué)基金重大研究計(jì)劃集成項(xiàng)目,，92254307，細(xì)胞器互作調(diào)控細(xì)胞自噬的機(jī)制和功能研究,，2023. 01-2025. 12,，150萬(wàn)元，在研,，合作主持 2. 上海教委前沿科學(xué)基地,，細(xì)胞穩(wěn)態(tài)和疾病，2021/08-2026/08, 2500萬(wàn)元,，在研,，主持 3. 國(guó)家自然科學(xué)基金委中德合作交流項(xiàng)目（Mobility programme），M-0140,，Rab 及其調(diào)控蛋白在HOPS介導(dǎo)的自噬體-溶酶體融合中的作用及相關(guān)神經(jīng)退行性疾病的研究,，2021/01-2023/12,150萬(wàn)元，在研,，主持 4. 科技部骨干項(xiàng)目,，2019YFA0508600，線粒體和溶酶體穩(wěn)態(tài)維持的蛋白質(zhì)機(jī)器及其在神經(jīng)退行性疾病中的作用（細(xì)胞器穩(wěn)態(tài)調(diào)控的蛋白質(zhì)機(jī)器在神經(jīng)退變的病理及功能解析）,，2020/01-2024/12,，249萬(wàn)元，在研,，主持 5. 上海市2020年度“科技創(chuàng)新行動(dòng)計(jì)劃基礎(chǔ)研究領(lǐng)域項(xiàng)目”,，20JC1411100，靶向自噬的別構(gòu)小分子的鑒定及其在腫瘤治療中的應(yīng)用研究,，2020/10-2023/09,，400萬(wàn)元，在研,，主持 6. 國(guó)家自然科學(xué)基金重大研究計(jì)劃重點(diǎn)支持項(xiàng)目,，91957204,，STX18介導(dǎo)的脂滴融合與脂滴自噬的機(jī)制與功能研究，2020/01-2023/12,330萬(wàn)元,，在研,，主持 7. 上海市科技人才計(jì)劃項(xiàng)目，19XD1402200,自噬與腫瘤,，2019/05-2022/04,，40萬(wàn)元，結(jié)題,，主持 8. 國(guó)家自然科學(xué)基金重大研究計(jì)劃重點(diǎn)支持項(xiàng)目,，91754205，細(xì)胞自噬體,，溶酶體及內(nèi)質(zhì)網(wǎng)的相互作用及調(diào)控,，2018/01-2021/12，255萬(wàn)元,，結(jié)題,，主持 9. 國(guó)家自然科學(xué)基金面上項(xiàng)目，31771523,，營(yíng)養(yǎng)感受激酶mTORC1對(duì)自噬特異的脂質(zhì)磷酸化激酶的關(guān)鍵性調(diào)控機(jī)制研究,，2018/01-2021/12，61萬(wàn)元,，結(jié)題,，主持
論文與專著 >>>
1. Zhang J*, Hansen CT, Wang JH, Zhang ZL, Wang X, Qiao YH, Jiao HK, Michaud M, Kepp O, Jaattela M, Kroemer G*, Zhong Q*. Necrocide 1 mediates necrotic cell death and immunogenic response in human cancer cells. Cell Death & Disease, 2023 April 05;14:238. 2. Cao M*, Zou X, Li C, Lin S, Wang N, Zou Z, Ye Y, Seeman J, Levine B, Tang Z, Zhong Q*. An Actin Filament Branching Surveillance System Regulates Cell Cycle Progression, cytokinesis and Primary Ciliogenesis. Nature Communications. 2023 March 27;14:1687. 3. Zheng Z, Yan G, Li X, Fei Y, Sun L, Yu H, Niu Y, Gao W, Zhong Q*, Yan X*. Lysine crotonylation regulates leucine deprivation induced autophagy by an 14-3-3ε-PPM1B axis. Cell Rep. 2022 Dec 20;41(12):111850. PMID: 36543144. 4. Yan G, Li X, Zheng Z, Gao W, Chen C, Wang X, Cheng Z, Yu J, Zou G, Farooq MZ, Zhu X, Zhu W, Zhong Q*, Yan X*. KAT7-mediated CANX (calnexin) crotonylation regulates leucine-stimulated MTORC1 activity. Autophagy. 2022 Dec;18(12):2799-2816. PMID: 35266843. 5. Leng H, Zhang H, Li L, Zhang S, Wang Y, Chavda SJ, Galas-Filipowicz D, Lou H, Ersek A, Morris EV, Sezgin E, Lee YH, Li Y, Lechuga-Vieco AV, Tian M, Mi JQ, Yong K, Zhong Q, Edwards CM, Simon AK*, Horwood NJ*. Modulating glycosphingolipid metabolism and autophagy improves outcomes in pre-clinical models of myeloma bone disease. Nat Commun. 2022 Dec 22;13(1):7868. PMID: 36550101. 6. Lukmantara I, Chen F, Mak HY, Zadoorian A, Du X, Xiao FN, Norris DM, Pandzic E, Whan R, Zhong Q, Yang H*. PI(3)P and DFCP1 regulate the biogenesis of lipid droplets. Mol Biol Cell. 2022 Dec 1;33(14):ar131. PMID: 36129766. 7. 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 8. 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. 9. 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. 10. Klionsky……Zhong Q, Galluzzi L, Pietrocola F. Autophagy in major human diseases. EMBO J. 2021, Aug. PMID: 34459017. 11. 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. 12. 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. 13. 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 14. Klionsky et al., Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2021, Jan;17(4):1-382. PMID: 33634751. 15. 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. 16. Galluzzi L……Zhong Q, Kroemer G. Molecular definitions of autophagy and related processes. EMBO J. 2017 Jul 3;36(13). PMID: 28596378. 17. 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. 18. Klionsky et al., Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2016, 12(1):1-222. PMID: 26799652. 19. Li L, Zhong Q. Autophagosome-lysosome fusion: PIs to the rescue. EMBO. 2016;35(17):1845-7. PMID: 27440401. 20. 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. 21. 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. 22. 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. 23. 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. 24. Zhi X and Zhong Q. Autophagy in Cancer. F1000Prime Rep. 2015;7:18. PMID: 25750736. 25. Zhang J, Zhong Q. Histone deacetylase inhibitors and cell death. Cell Mol Life Sci. 2014;71(20):3885-901. PMID: 24898083. 26. Tang Z, Zhu M, Zhong Q. Self-eating to remove cilia roadblock. Autophagy. 2014;10(2):379-81. PMID: 24343661. 27. 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 28. Nazarko V and Zhong Q. ULK1 targets Beclin-1 in autophagy. Nat Cell Biol. 2013;15(7):727-8. PMID: 23817237. 29. 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. 30. 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. 31. Chen D, Zhong Q. A tethering coherent protein in autophagosome maturation. Autophagy. 2012;8(6):985-6. PMID: 22617511. 32. 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. 33. 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. 34. Klionsky et al., Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2012, Apr;8(4):455-544. PMID: 22966490. 35. 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. 36. 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. 37. 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 38. Wilz L, Fan W, Zhong Q. Membrane curvature response in autophagy. Autophagy. 2011 Oct;7(10):1249-50. PMID: 21738011. 39. 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. 40. 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. 41. 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. 42. 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. 43. Sun Q, Fan W, Zhong Q. Regulation of Beclin 1 in autophagy. Autophagy. 2009 Jul 24;5(5):713-6. PMID: 19372752. 44. 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. 45. 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 46. 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. 47. 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. 48. 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. 49. 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. 50. 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. 51. 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. 52. 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 53. 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. 54. Zhong Q, Chen Y, Jones D, and Lee W-H: Perturbation of TSG101 Protein Affects Cell Cycle Progression. Cancer Res, 1998, 58: 2699-2702. 55. 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.
|
