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个人简介

教育经历 1988 - 1993 湖南医科大学,医学检验学士 1995 - 1998 华西医科大学,生物化学硕士 1999 - 2001 美国俄亥俄州Bowling Green州立大学,计算机科学硕士 1998 - 2002 美国俄亥俄州Bowling Green州立大学,生命科学博士 工作经历 1993 - 1995 华西医科大学附二院检验科,检验医师 2003 - 2004 美国Emory大学,博士后,导师Junmin Peng 2005 - 2007 美国Scripps研究所,博士后,导师John Yates 2007 - 2012 美国Scripps研究所,Staff Scientist 2012 - 2013 中科院上海生命科学研究院生物化学与细胞生物学研究所,PI,博导 2013 - 至今 华东师范大学生命科学学院,教授/博导

研究领域

廖鲁剑教授于2002年12月在美国Bowling Green州立大学获得计算机科学硕士和生物科学/神经生物学博士学位,在美国Emory大学及加州Scripps研究所John Yates实验室从事博士后研究,后以Staff Scientist任职于Scripps 研究所。2012年5月回国任中科院上海生物化学与细胞生物学研究所/国家蛋白质科学研究中心研究员,获中科院上海生科院特殊人才计划支持。2013年8月担任华东师范大学生命医学研究所生物医学教授、博士生导师,建立功能蛋白质组学实验室。主要研究方向为利用蛋白质组学方法结合分子、细胞、动物等手段研究细胞器质量控制在神经退行性疾病发生中的作用。在确定神经退行性疾病主要病变的蛋白组成和定量蛋白质组学新方法探索做出开拓性的工作,成果发表于JBC,J Proteome Res, PNAS,Nat Methods。在SCI影响因子>5的各类专业期刊上发表第一或共同第一作者研究论文10篇,应邀综述1篇。利用高精度定量质谱的合作研究发现重要疾病模型的蛋白质差异表达和蛋白修饰,成果发表于Immunity,Cell,PNAS,Science,Nat Immunology,EMBO J,Nat Cell Biol等杂志。 在后基因组时代,系统研究细胞或机体的蛋白质在时间,空间水平的定量变化,翻译后修饰,以及蛋白复合体的动态变化,已经在许多方向为进一步理解生命过程的基本原理,深入了解重大疾病的发生发展机理开辟了新途径。基于液相色谱-高分辨质谱联用的蛋白组学在这些研究方向起着举足轻重的作用。本实验室利用先进的质谱技术,结合分子生物学、细胞生物学、生物化学何动物模型等多种研究手段,探索蛋白质及细胞器稳态在神经退行性疾病发病过程中的作用。尤其关注蛋白激酶和泛素连接酶的功能变化,以及线粒体和内质网质量控制系统的异常导致神经细胞退行性变的机理。 蛋白质组学技术开发 基于液相色谱-高分辨质谱的蛋白质组学已经在过去十年有了长足的发展。在技术上,蛋白质组学能在一次实验中常规鉴定出五-六千多个蛋白质。经过特殊的实验设计和样品处理,蛋白质组学能对不同的生物样品中蛋白质差异表达进行分析,也能大规模检测和定量蛋白质组的翻译后修饰。在蛋白质组学技术开发领域,我们主要关注以下问题: 大规模、深度覆盖地鉴定和定量磷酸化蛋白质组 利用定量质谱研究蛋白质-蛋白质之间相互作用 建立筛查在神经退行性疾病中起重要作用的蛋白酶底物的化学生物学方法 蛋白质及细胞器稳态在神经退行性疾病发病过程中的作用 神经退行性疾病,包括老年性痴呆(Alzheimer’s), 帕金森氏病(Parkinson’s), 肌萎缩性脊髓侧索硬化症(ALS)等,已经在有家族史的病人中找到多种基因突变。其中很多基因编码的蛋白质在神经系统的信号传导中起到举足轻重的作用,其中包括蛋白激酶,泛素连接酶和自噬相关蛋白质。我们建立基因突变的退行性疾病小鼠模型,利用定量质谱技术寻找差异蛋白及与这些蛋白相互作用的蛋白复合体,从中筛选出关键信号通路,进一步探索这些通路在神经退行性变中的作用。 利用定量磷酸化蛋白质组学方法(TMT)寻找蛋白PINK1激酶的底物和下游信号分子,已经这些底物在保护神经细胞免受氧化损伤的机制 利用定量蛋白质组学方法(SILAC)研究自噬蛋白缺失突变导致细胞器质量控制失常及神经退行性变的机理

近期论文

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通讯作者论文(*) Mao L, Chen J, Lu X, Yang C, Ding Y, Wang M, Zhang Y, Tian Y, Li X, Fu Y, Yang Y, Gu Y, Gao F, Huang J, Liao L*. Proteomic analysis of lung cancer cells reveals a critical role of BCAT1 in cancer cell metastasis. Theranostics. 2021, 11(19):9705-9720 Yan K, Yang Y, Zhang Y, Zhao W, Liao L*. Normalization Method Utilizing Endogenous Proteins for Quantitative Proteomics. J Am Soc Mass Spectrom. 2020, 31(7):1380–1388. PMID: 32268065 Wan H, Wang Q, Chen X, Zeng Q, Shao Y, Fang H, Liao X*, Li HS, Liu MG, Xu TL, Diao M, Li D, Meng B, Tang B, Zhang Z*, Liao L*. WDR45 contributes to neurodegeneration through regulation of ER homeostasis and neuronal death. Autophagy. 2020, 16(3):531-547. PMID: 31204559 Wang T, Wang J, Wang J, Mao L, Tang B, Vanderklish PW, Liao X*, Xiong Z*, Liao L*. HAP1 is an in vivo UBE3A Target that Augments Autophagy in a Mouse Model of Angelman Syndrome. Neurobiology of Disease. 2019, 132:104585.PMID: 31445164 Wang J, Lou SS, Wang T, Wu RJ, Li G, Zhao M, Lu B, Li YY, Zhang J, Cheng X, Shen Y, Wang X, Zhu ZC, Li MJ, Takumi T, Yang H, Yu X, Liao L*, Xiong ZQ*. UBE3A-mediated PTPA ubiquitination and degradation regulate PP2A activity and dendritic spine morphology. Proc Natl Acad Sci U S A. 2019, 116(25):12500-12505. PMID: 31160454 Wan H, Tang B, Liao X, Zeng Q, Zhang Z, Liao L*. Analysis of neuronal phosphoproteome reveals PINK1 regulation of BAD function and cell death. Cell Death & Diff. 2018, 25:901-917 PMID:29234155 Gao Y, Liu X, Tang B, Li C, Kou Z, Li L, Liu W, Wu Y, Kou X, Li J, Zhao Y, Yin J, Wang H, Chen S, Liao L*, Gao S*. Protein Expression Landscape of Mouse Embryos during Pre-implantation Development. Cell Reports. 2017, 21(13):3957-3969. PMID: 29281840 Wei W, Mao A, Tang B, Zeng Q, Gao S, Liu X, Lu L, Li W, Du JX, Li J, Wong J*, Liao L*. Large-Scale Identification of Protein Crotonylation Reveals Its Role in Multiple Cellular Functions. J Proteome Res. 2017, 16(4):1743-1752.PMID:28234478 Tan GH, Liu YY, Wang L, et al., Liao LJ*, Wu ZY*, Xiong ZQ*. PRRT2 deficiency induces paroxysmal kinesigenic dyskinesia by regulating synaptic transmission in cerebellum. Cell Res. 2018, Jan. 28(1):90-110. Cheng TL, Chen J, Wan H, Tang B, Tian W, Liao L*, Qiu Z*. Regulation of mRNA splicing by MeCP2 via epigenetic modifications in the brain. Sci Rep. 2017, 17;7:42790. PMID: 28211484 Tang B, Wang T, Wan H, Han L, Qin X, Zhang Y, Wang J, Yu C, Berton F, Francesconi W, Yates JR, Vanderklish PW, Liao L*. Fmr1 deficiency promotes age-dependent alterations in the cortical synaptic proteome. Proc Natl Acad Sci U S A. 2015, 112(34): E4697-706. PMID:26307763 Qin X, Zheng C, Yates JR 3rd, Liao L*. Quantitative phosphoproteomic profiling of PINK1-deficient cells identifies phosphorylation changes in nuclear proteins. Mol BioSyst. 2014, 10(7):1719-29. PMID:24626860 其它代表性论文(#共同第一作者) Liu Y, Zhang P, Wu Q, Fang H, Wang Y, Xiao Y, Cong M, Wang T, He Y, Ma C, Tian P, Liang Y, Qin LX, Yang Q, Yang Q, Liao L, Hu G. Long non-coding RNA NR2F1-AS1 induces breast cancer lung metastatic dormancy by regulating NR2F1 and ΔNp63. Nat Commun. 2021 Sep 2;12(1):5232. Nakamura T, Oh CK, Liao L, Zhang X, Lopez KM, Gibbs D, Deal AK, Scott HR, Spencer B, Masliah E, Rissman RA, Yates JR 3rd, Lipton SA. Noncanonical transnitrosylation network contributes to synapse loss in Alzheimer's disease. Science. 2021 Jan 15;371(6526):eaaw0843. Xiao X, Liu P, Li D, Xia Z, Wang P, Zhang X, Liu M, Liao L, Jiao B, Ren R. Combination therapy of BCR-ABL-positive B cell acute lymphoblastic leukemia by tyrosine kinase inhibitor dasatinib and c-JUN N-terminal kinase inhibition. J Hematol Oncol. 2020 Jun 18;13(1):80. Dai P, Wang X, Gou LT, Li ZT, Wen Z, Chen ZG, Hua MM, Zhong A, Wang L, Su H, Wan H, Qian K, Liao L, Li J, Tian B, Li D, Fu XD, Shi HJ, Zhou Y, Liu MF. A Translation-Activating Function of MIWI/piRNA during Mouse Spermiogenesis. Cell. 2019 Dec 12;179(7):1566-1581. PMID: 31835033 Fang L, Teng H, Wang Y, Liao G, Weng L, Li Y, Wang X, Jin J, Jiao C, Chen L, Peng X, Chen J, Yang Y, Fang H, Han D, Li C, Jin X, Zhang S, Liu Z, Liu M, Wei Q, Liao L, Ge X, Zhao B, Zhou D, Qin HL, Zhou J, Wang P. SET1A-Mediated Mono-Methylation at K342 Regulates YAP Activation by Blocking Its Nuclear Export and Promotes Tumorigenesis. Cancer Cell. 2018, 34(1):103-118.e9. PMID: 30008322 Zhao Z, Xu D, Wang Z, Wang L, Han R, Wang Z, Liao L, Chen Y. Hepatic PPARα function is controlled by polyubiquitination and proteasome-mediated degradation through the coordinated actions of PAQR3 and HUWE1. Hepatology. 2018, 1368(1):289-303. PMID:29331071 Wang T, Yu Q, Li J, Hu B, Zhao Q, Ma C, Huang W, Zhuo L, Fang H, Liao L, Eugene Chin Y, Jiang Y. O-GlcNAcylation of fumarase maintains tumour growth under glucose deficiency. Nat Cell Biol. 2017, 19(7):833-843. PMID:28628081 Xu DQ, Wang Z, Wang CY, et al., Liao LJ, Chen Y. PAQR3 controls autophagy by integrating AMPK signaling to enhance ATG14L-associated PI3K activity. EMBO J. 2016, 35(5):496-514. PMID:26834238 Park Y, Jin HS, Lopez J, Lee J, Liao L, Elly C, Liu YC. SHARPIN controls regulatory T cells by negatively modulating the T cell antigen receptor complex. Nat Immunol. 2016 Mar;17(3):286-96. PMID:26829767 Okamoto S, Nakamura T, Cieplak P, Chan SF, Kalashnikova E, Liao L, Saleem S, Han X, Clemente A, Nutter A, Sances S, Brechtel C, Haus D, Haun F, Sanz-Blasco S, Huang X, Li H, Zaremba JD, Cui J, Gu Z, Nikzad R, Harrop A, McKercher SR, Godzik A, Yates JR 3rd, Lipton SA.S-nitrosylation-mediated redox transcriptional switch modulates neurogenesis and neuronal cell death. Cell Rep. 2014 Jul 10;8(1):217-28. Li K, Zhou T, Liao L, Yang Z, Wong C, Henn F, Malinow R, Yates JR, Hu H. βCaMKII in Lateral Habenula Mediates Core Symptoms of Depression. Science. 2013;341:1016-1020. Jin HS, Liao L, Park Y, Liu YC. Neddylation pathway regulates T-cell function by targeting an adaptor protein Shc and a protein kinase Erk signaling. Proc Natl Acad Sci U S A. 2013;110(2):624-9 Sando R 3rd, Gounko N, Pieraut S, Liao L, Yates JR 3rd, and Maximov A. HDAC4 Governs Transcriptional Programs Essential for Synaptic Development and Function. Cell. 2012; 151(4):821-34 Banerjee S, Liao L, Russo R, Nakamura T, McKercher SR, Okamoto S, Haun F, Nikzad R, Zaidi R, Holland E, Eroshkin A, Yates JR 3rd, Lipton SA. Isobaric tagging-based quantification by mass spectrometry of differentially regulated proteins in synaptosomes of HIV/gp120 transgenic mice: Implications for HIV-associated neurodegeneration. Exp Neurol. 2012; 236(2):298-306 Liao L, Sando RC, Farnum JB, Vanderklish PW, Maximov A, and Yates JR 3rd. 15N labeled brain enable quantification of proteome and phosphoproteome in neurons. J Proteome Res. 2012; 11(2):1341-53 Hart JR, Liao L, Yates JR 3rd, Vogt PK. An essential role of signal transducer and activator of transcription 3 in phosphatidylinositol 3-kinase-induced oncogenic transformation. Proc Natl Acad Sci USA. 2011; 108(32):13247-52 Hart JR#, Liao L#, Ueno L, Yates JR 3rd, Vogt PK. Protein expression profiles of C3H 10T1/2 murine fibroblasts and of isogenic cells transformed by the H1047R mutant of phosphoinositide 3-kinase (PI3K). Cell Cycle. 2011; 10(6):971-6 Huang H#, Jeon M#, Liao L#, Yang C, Elly C, Yates JR, and Liu YC. K33-Linked Polyubiquitination of T Cell Receptor-ζ Regulates Proteolysis-Independent T Cell Signaling. Immunity. 2010; 33(1):60-70 Ramya TNC, Weerapana E, Liao L, Zenga Y, Tatenoa H, Liao L, Hana S, Yates JR, Cravatta BF, and Paulson JC. In situ trans ligands of CD22 identified by glycan-protein photo-cross-linking enabled proteomics. Mol Cell Proteomics. 2010; 9(6):1339-51 Liao L#, McClatchy DB#, Yates JR. Primer: shotgun proteomics in neuroscience. (Review) Neuron. 2009; 63(1):12-26 Park SK#, Liao L#, Kim JY, and Yates JR. A computational approach to correct arginine-to-proline conversion in quantitative proteomics. Nature Methods. 2009; 6(3):184-185 Liao L, Park SK, Xu T, Vanderklish PW, and Yates JR. Quantitative proteomic analysis of primary neurons reveals diverse changes in synaptic protein content in fmr1 knockout mice. Proc Natl Acad Sci USA. 2008; 105(40):15281-6 Liao L#, McClatchy DB#, Park SK, Xu T, Lu B and Yates JR. Quantitative analysis of brain nuclear phosphoproteins identifies developmentally regulated phosphorylation events. J Proteome Res. 2008; 7(11):4743-55 Denny, P.#, Hagen, F.K.#, Hardt, M.#, Liao, L.#, Yan, W.#, et al. The proteomes of human parotid and submandibular/sublingual gland saliva collected as the ductal secretions. J Proteome Res. 2008, 7(5):1994-2006. (* Co-first author) Xia Q#, Liao L#, Cheng D, Duong D, Gearing M, Lah JJ, Levey AI, and Peng J. Identification of novel kinases and ubiquitin ligases associated with Lewy bodies by comparative proteomics. Frontiers in Bioscience. 2008; 13:3850-6 McClatchy DB, Liao L, Park SK, Venable J, and Yates JR. Quantification of the synaptic proteome of the rat cerebellum during postnatal development. Genome Res. 2007; 17(9):1378-88 Liao L, Pilotte J, Xu T, Wong CL, Edelman GM, Vanderklish PW, and Yates JR. BDNF induces widespread changes in synaptic protein content and upregulates the translation machinery components: an analysis using high-throughput proteomics. J Proteome Res. 2007; 6(3):1059-71 Yates JR, Corciorva D, Liao L, Zabrouscov V. Performance of the LTQ-Orbitrap for peptide analysis. Anal Chem. 2006; 78(2):493-500 Liao L, Cheng D, Wang J, Losik T, Duong D, Gearing M, Rees H, Lah JJ, Levey AI, Peng J. Proteomic characterization of postmortem amyloid plaques isolated by laser capture microdissection. J Biol Chem. 2004; 279(35): 37061-8

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