个人简介
邹贻龙(1987-), 湖北荆州人。2005-2009年就读于清华大学生命科学与技术系并获本科学位，随后于2016年获得美国纽约纪念斯隆凯特琳癌症中心 (Memorial Sloan Kettering Cancer Center) 癌症生物学博士学位，师从导师Dr. Joan Massagué。博士期间，邹博士曾开创利用Translating Ribosome Affinity Purification and Sequencing (TRAP-Seq) 技术研究已广泛转移的癌细胞的在体基因表达谱的先例。2016年至今，邹博士同时在波士顿博德研究所 (Broad Institute of MIT and Harvard) 以及哈佛大学化学生物学系从事博士后研究，师从导师Dr. Stuart L. Schreiber。其博士后研究阐释了透明细胞癌中的脂代谢异常和对于铁死亡的独特敏感性，发现了细胞铁死亡执行中的关键蛋白，并揭示了决定细胞铁死亡敏感性的重要分子机制。邹博士已以第一作者或通讯作者身份在Nature (in press), Nature Chemical Biology, Cell Stem Cell, Genes and Development和Nature Communications等期刊发表多篇学术论文，曾受邀在Cell Chemical Biology撰写综述文章，并多次担任包括Nature Chemical Biology 和Nature Communications等学术期刊的审稿人。
曾获奖项
2022 “35 Innovators Under 35 (TR35)” in China 奖
2020 美国NIH Pathway-to-Independence K99/R00 奖
2019 Broad Institute Shark Tank 奖
2012 The Grayer Fellowship, Memorial Sloan Kettering Cancer Center
2009 本科生优秀科研奖一等奖，清华大学生命科学学院
2009 international Genetically Engineered Machine (iGEM) competition, MIT, 铜奖(任清华大学代表队队长)
2008 清华大学年度“科创之星”
研究方向
脂类是细胞最基本的组成成分，也是界定生命体与非生命体的最关键因素之一。人体类脂质的多样性令人叹为观止；但是我们对每一类脂质的功能的理解却已经停滞多年未有突破。近年来，质谱技术的突飞猛进首次让大规模分析细胞脂质成为可能，并鉴定出大量具有特殊理化性质与生物活性的脂类分子，将这一领域再次推向高潮。本实验室（功能脂质组学与代谢调控实验室）广泛关注细胞内脂质的多样性，可塑性，代谢途径，生理功能以及由脂类代谢异常引起的疾病机理。我们的主要研究手段包括细胞生物学，化学生物学，遗传学，生物信息学，和疾病的动物模型等。具体的研究方向包括:
1) 探索由脂类修饰引起的细胞死亡例如铁死亡通路的分子机制与病理学作用。
铁死亡是一种由高度不饱和磷脂的过氧化修饰的过量聚集引起的细胞应激性死亡途径。其形态变化，死亡历程和分子机制均有别于常规的细胞凋亡等程序性死亡途径。近年的研究发现铁死亡在各种慢性或急性的器官衰竭过程中起到突出的作用，点燃了通过抑制铁死亡的发生来缓解这些疾病的希望。同时，研究发现部分癌症细胞对铁死亡也比正常细胞更加敏感，从理论上提供了一种靶向诱导癌细胞死亡的新思路。本实验室将重点关注铁死亡通路中悬而未决的重要问题，例如磷脂过氧化修饰的化学基础与催化机制，并将结合化学生物学与疾病的动物模型来开发新一代的铁死亡激动剂与抑制剂。
2) 寻找脂质在多种人类细胞分化过程中的变化，功能与调控机理。
人体细胞的形态和功能丰富多样，其结构基础的很大一部分是由细胞膜上的特定脂质成分与排列方式决定的。但是脂质组成分的变化具体怎样影响细胞的结构与功能却尚未被充分了解。我们前期的探索提示，干细胞在分化成为功能各异的成熟细胞类型的过程中，其脂质组也会发生巨大的变化。我们猜测这些变化对细胞的物理形态，能量代谢，信号转导等会产生深刻的影响，并直接为成熟细胞的品系特异性功能提供支持。为了系统性的研究这一问题，本实验室将着重构建一个全面的“哺乳类细胞脂质组图谱”，来协助发现在不同细胞类型之间有差异性分布的脂类分子，从而可以有针对性的研究这些分子的生物学功能和调控机制。我们相信这一研究将为我们对脂质的深入了解打开一扇新的窗户。
3) 鉴定脂类代谢在实体肿瘤发生，发展，转移与抗药性中的作用。
肿瘤发生和发展的每一步都需要相应的信号通路和代谢程序的支持，寻找这些支持机制成为设计肿瘤靶向治疗药物的基本思路。而肿瘤细胞与正常细胞的结构性差异，例如细胞膜的组成和能量储存的方式仍然相对未知。因为肿瘤在转移和获得抗药性的过程中会面临严苛微环境的考验，并需要随时变换形态来适应新的环境，我们预测肿瘤细胞脂质组的相应变化将会在这些过程中起到关键的作用。本实验室将结合癌症的动物学模型和遗传与化学生物学等手段来研究脂类代谢在癌症发展，转移与规避药物等过程中的作用和机制。
同时，基于以上研究中产生的新的生物学发现，我们将采用化学生物学途径建立新型的脂类检测与追踪的工具与方法，并开发针对特定脂类代谢通路靶点在相关疾病中的新型药物。
更多研究细节，请参见: https://www.yilongzou-lab.com/research
代表论文
1. Han JR, Yang Y, Wu TW, Shi T-T, Li W, Zou Y#. A minimally-invasive method for serial cerebrospinal fluid collection and injection in rodents with high survival rates. Biomedicines (in press)
2. Naowarojna N*, Wu TW*, Pan Z, Li M, Han JR, Zou Y#. Dynamic Regulation of Ferroptosis by Lipid Metabolism. Antioxid Redox Signal. 2023 May 2. doi: 10.1089/ars.2023.0278. PMID: 36974367.
3. Wang F, Naowarojna N, and Zou Y#. Stratifying ferroptosis sensitivity in cells and tissues by photochemical activation of lipid peroxidation and imaging. STAR Protocols 2022 Mar 23;3(2):101189. doi: 10.1016/j.xpro.2022.101189. PMID: 35345595.
4. Wang F*, Graham ET*, Naowarojna N*, Shi Z*, Wang Y, Xie G, Zhou L, Salmon W, Jia J-M, Wang X, Huang Y, Schreiber SL#, and Zou Y#. PALP: a rapid imaging technique for stratifying ferroptosis sensitivity in normal and tumor tissues in situ. Cell Chemical Biology 2021 Nov 18:S2451-9456(21)00478-5. doi: 10.1016/j.chembiol.2021.11.001. PMID: 34813762.
Commented by: Ritho and Dixon, Cell Chemical Biology 2022
5. Pan Z*, Naowarojna N*, Wang Y, Hu M, and Zou Y#. Neutrophil ferroptotic death promotes autoimmune pathogenesis. SCIENCE CHINA Life Sciences (Invited Commentary) 2021 Oct 27. doi: 10.1007/s11427-021-2014-4. PMID: 34716854.
6. Shi Z*, Naowarojna N*, Pan Z, Zou Y#. Multifaceted mechanisms mediating cystine starvation-induced ferroptosis. Nature Communications 2021 Aug 09. doi: 10.1038/s41467-021-25159-5. (*co-first author)
7. Zou Y*,#, Henry WS*, Ricq EL*, Graham ET, Maretich P, Paradkar S, Phadnis VV, Boehnke N, Deik AA, Reinhardt F, Eaton JK, Ferguson B, Wang W, Fairman J, Keys H, Dančík V, Clish CB, Clemons PA, Hammond PT, Boyer LA, Weinberg RA#, and Schreiber SL#. Plasticity in ether-lipids promote ferroptosis susceptibility and evasion. Nature 585(7826): 603-608. doi: 10.1038/s41586-020-2732-8. (*co-first author, #co-corresponding author)
Commented by:
· Conrad et al., Cell Research 2020;
· Tang and Kroemer, Signal Transduction and Targeted Therapies, 2020.
· Lee, Zhuang and Gan, Journal of Genetics and Genomics, 2021
· Balgoma and Hedeland, Trends in Endocrinology and Metabolism 2021
8. Zou Y# & Schreiber SL#. Progress in understanding ferroptosis and challenges in its targeting for therapeutic benefit. Cell Chemical Biology 2020 April; 27(4): 463-471. https://doi.org/10.1016/j.chembiol.2020.03.015 (Perspective) (#co-corresponding author).
9. Zou Y*,#, Li H*, Graham ET, Deik AA, Eaton JK, Wang W, Sandoval-Gomez G, Clish C, Doench JG, & Schreiber SL#. Cytochrome P450 oxidoreductase contributes to phospholipid peroxidation in ferroptosis. Nature Chemical Biology 2020 Mar;16(3):302-309. PMID: 32080622. doi: https://doi.org/10.1038/s41589-020-0472-6 (*co-first author, #co-corresponding author)
Commented by: Gan et al., Protein & Cell 2021.
Collected in: Hadian and Stockwell, Snapshot: Ferroptosis Cell 2020
10. Aragón A*, Wang Q*, Zou Y*, Morgani SM, Ruiz L, Kaczmarska Z, Su J, Torner C, Tian L, Hu J, Shu W, Agrawal S, Márquez JA, Hadjantonakis A-K, Macias MJ, and Massagué J. Structural basis for distinct roles of SMAD2 and SMAD3 in FOXH1 pioneer directed TGF-β signaling. Genes&Development 2019 Nov 1;33(21-22):1506-1524. doi:10.1101/gad.330837.119. (*co-first author, listed in alphabetical order.)
11. Li H, Ning S, Ghandi M, Kryukov GV, Gopal S, Deik AA, Souza A, Pierce K, Keskula P, Hernandez D, Ann J, Shkoza D, Apfel V, Zou Y, Vazquez F, Barretina J, Pagliarini RA, Galli GG, Root DE, Hahn WC, Tsherniak A, Giannakis M, Schreiber SL, Clish CB, Garraway LA, and Sellers WR. The landscape of cancer cell line metabolism. Nature Medicine 2019 May;25(5):850-860. PMID: 31068703.
12. Zou Y, Palte MJ, Deik AA, Li H, Eaton JK, Wang W, Tseng Y-Y, Deasy R, Alimova M, Dančik V, Leshchiner ES, Viswanathan VS, Signoretti S, Choueiri TK, Boehm JS, Wagner BK, Doench J, Clish CB, Clemons PA, and Schreiber SL. A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis. Nature Communications 2019 Apr 8;10(1):1617. PMID: 30962421. doi: https://doi.org/10.1038/s41467-019-09277-9
13. Su J, Morgani SM, David CJ, Wang Q, Er EE, Huang Y-H, Basnet H, Zou Y, Shu W, Hendrickson RC, Soni RK, Hadjantonakis A-K, and Joan Massagué. TGF-β Orchestrates Fibrogenic and Developmental EMTs Through the RAS Effector RREB1. Nature 2020 Jan; 577(7791): 566-571. PMID: 31915377.
14. Er EE, Valiente M, Ganesh K, Zou Y, Agrawal S, Griscom B, Giancotti F, Schachner M, Malladi S, and Massagué J. Pericytic Spreading of Disseminated Cancer Cells Activates YAP for Metastatic Outgrowth. Nature Cell Biology 2017 July 23. PMID: 30038252.
15. Martin-Malpartida P, Batet M, Kaczmarska Z, Freier R, Gomes T, Aragon E, Zou Y, Wang Q, Xi Q, Ruiz L, Vea A, Marquez JA, Massagué J and Macias M. Structural basis for genome wide recognition of 5-bp GC motifs by SMAD transcription factors. Nature Communications 2017 Dec 12; 8(1):2070. PMID: 29234012.
16. Boire A, Zou Y, Shieh J, Macalinao DG, Pentsova E and Massagué J. Complement Component 3 Adapts the Cerebrospinal Fluid for Leptomeningeal Metastasis. Cell 2017 Mar 9;168(6):1101-1113. PMID: 28283064
17. Wang Q*, Zou Y*, Nowotschin S, Li Q, Soh C-L, Kim SY, Xi Q, Zhang C, Su J, Shu W, Huangfu D, Hadjantonakis A-K and Massagué J. The p53 family coordinates Wnt and Nodal Inputs for mesendoderm differentiation of embryonic stem cells. Cell Stem Cell 2017 Jan 5;20(1):70-86. doi: https://doi.org/10.1016/j.stem.2016.10.002. PMID: 27889317. (*Co-first author)
Commented by:
· Hamilton and Brickman, Cell Stem Cell 2017
· Okuda, Uranishi and Suzuki, Stem Cell Investigation 2017
18. Malladi S, Macalinao DG, Jin X, He L, Basnet H, Zou Y, de Stanchina E and Massagué J. Metastatic latency and immune evasion through autocrine inhibition of WNT. Cell 2016 Mar 24;165(1):45-60. PMID: 27015306.
19. David CJ, Huang Y-H, Chen M, Su J, Zou Y, Bardeesy N, Iacobuzio-Donahue CA and Massagué J. TGF-β tumor suppression through a lethal EMT. Cell 2016 Feb 25;164(5):1015-30. PMID: 26898331.
20. Obenauf AC, Zou Y*, Ji AL*, Vanharanta S, Shu W, Shi H, Kong X, Bosenberg MC, Wiesner T, Rosen N, Lo RS and Massagué J. Therapy-induced tumour secretomes promote resistance and tumour progression. Nature. 2015 Apr 16;520(7547):368-72. PMID: 25807485. (*Equal contribution)
21. Vanharanta S, Marney CB, Shu W, Valiente M, Zou Y, Mele A, Darnell RB and Massagué J. Loss of the multifunctional RNA-binding protein RBM47 as a source of selectable metastatic traits in breast cancer. Elife. 2014 Jun 4;3. PMID: 24898756.
22. Ji AL, Obenauf AC, Zou Y, Vanharanta S, Jin X and Massagué J. Selection for vemurafenib resistant melanoma cells leads to an increase in metastatic potential. Pigment Cell&Melanoma Research. 2013 Nov 1;26(6): 962-963.
23. Zhang XH, Jin X, Malladi S, Zou Y, Wen YH, Brogi E, Smid M, Foekens JA and Massagué J. Selection of bone metastasis seeds by mesenchymal signals in the primary tumor stroma. Cell. 2013 Aug 29;154(5):1060-73. PMID: 23993096.
24. Morris LG, Kaufman AM, Gong Y, Ramaswami D, Walsh LA, Turcan Ş, Eng S, Kannan K, Zou Y, Peng L, Banuchi VE, Paty P, Zeng Z, Vakiani E, Solit D, Singh B, Ganly I, Liau L, Cloughesy TC, Mischel PS, Mellinghoff IK and Chan TA. Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation. Nature Genetics. 2013 Mar;45(3):253-61. PMID: 23354438.
25. Chen R, Zou Y, Mao D, Sun D, Gao G, Shi J, Liu X, Zhu C, Yang M, Ye W, Hao Q, Li R and Yu L. The general amino acid control pathway regulates mTOR and autophagy during serum/glutamine starvation. Journal of Cell Biology. 2014 Jul 21;206(2):173-82. PMID: 25049270.
26. Zhao Q, Li S, Xue F, Zou Y, Chen C, Bartlam M and Rao Z. Structure of the main protease from a global infectious human coronavirus, HCoV-HKU1. Journal of Virology. 2008 Sep;82(17):8647-55. PMID: 18562531.
查看所有论文: https://www.yilongzou-lab.com/publications
联系方式
Email: zouyilong@westlake.edu.cn
本实验室现有多个博士后，博士研究生，科研助理等岗位。我们致力于为科研人员提供优越的学术研究平台，充足的自主探索空间，积极健康的实验室文化，跨学科的科研训练环境和长期的职业发展支持，希望有志于原创性研究的青年学者能够加盟来一起探索生命的规律。详情请见实验室网站：https://www.yilongzou-lab.com/join-us-1