哈尔滨工业大学

陈西

发布日期:2024-05-10 浏览次数:

导师简介 招生招聘 论文论著 Photos/Members Lab News 新建主栏目 课题组公众号 名称 关注前沿交叉及生物、医学应用 导师简介 名称 陈西,国家级青年人才、黑龙江省优青、哈工大生命科学中心研究员、博导,研究领域是抗体与临近诱导的化学生物学。主要方向包括(1)化学光遗传与光化学生物学,(2)纳米抗体靶向蛋白降解,以及(3)纺锤体组装与肿瘤治疗。2012-2018年在德国马普分子生理所和马普化学基因组学中心工作,2018-2019年作为高级研究学者在美国普林斯顿大学分子生物学院工作。期间,提出并发展了化学光遗传(chemo-optogenetics),将光遗传学与化学相结合,发展出了先进的光调控细胞进程的新技术。目前共发表论著约三十篇,代表性成果包括近5年来以独立通讯等发表高水平研究论文(IF>15)多篇,包括Adv Sci(2024)cover、Nat Commun(2023) 、J Am Chem Soc(2023) covery、Cell Discov(2020)、Angew Chem Int Ed(2018/ 2018 VIP paper/ 2017 Hot paper)等等;另外还撰写有专著章节3篇(Elsevier 2021/ Spinger Nature 2019/ Wiley VCH 2017 )、申请和获得PCT国际发明专利及中国发明专利多项。 荣誉/认可 名称 > 国家级青年人才 > 黑龙江省优青获得者 >《Bioengineering》客座编辑(Guest Editor) > Nature系列杂志审稿专家 > 中国化学会CCS会员 > 中国细胞生物学学会CSCB会员 > 生物化学与分子生物学学会CSBMB会员 教授课程 名称 ”生命BIO-X导论“之《化学生物学》 高等教育 名称 乌尔姆大学 博士(High Honors学位) 2010年-2012年 新加坡国立大学 硕士 2008年-2010年 四川大学(创新班)学士 2004年-2008年 工作经历 名称 哈尔滨工业大学 生命科学中心 研究员(PI) 2020年-今 普林斯顿大学 分子生物学院 高级研究学者 2018年-2019年 多特蒙德生物医药中心(BioMedicine Centre Dortmund) 2013年-2018年 马普化学基因组学中心 博士后(Postdoc) 2013年-2018年 马普分子生理所 博士后(Postdoc) 2012年-2018年 巴斯夫公司·亚太 2008年 实验室名称 名称 哈尔滨工业大学 化学生物学与前沿生物技术实验室(Laboratory of Chemical Biology & Frontier Biotechnologies) “抗体与临近诱导的化学生物学” 招生招聘 名称 课题组招聘招收助理教授、博士后、博士、硕士、技术员/科研助理、本科生、实习生 博士后:本课题组招聘化学生物学、前沿生物技术、合成生物学等方向的博士后1-2名,提供工大相应的薪资和福利,申请者可以直接联系PI邮箱(chenxihit@hit.edu.cn),并提供3名推荐专家的联系方式。 技术员:本课题组招聘对化学生物学、交叉科学、前沿生物技术,细胞分裂等研究领域感兴趣的技术员(研究生学历),提供五险一金等福利。申请者可以直接联系PI邮箱,优秀者可获得优先读博资格。 博士生:1-2名。学校通过“申请-考核”、“快响”等制度招收博士。PI老师邮箱:chenxihit@hit.edu.cn 硕士生:1-2名。 本科生:欢迎本科生提前进入实验室实习。对于进入课题组实习的本科生,表现优秀者也会给与实习资助,并获得读硕士和博士的优先机会,以及其它参加会议等相关学术奖励。本科生既可以参与到其它课题当中,也有机会根据自己兴趣主导一个合适的课题。 额外津贴制度:本课题组还会给实验室的博士生、硕士生、实习生以及本科生均提供除了学校奖学金以及学院中心的补贴之外额外的生活津贴! 科研奖励制度:本课题组给予发表高水平论文的学生第一作者以及共同第一作者身份据贡献提供科研奖励! 参加会议奖励:对于发表高水平研究论文的学生,实验室支持参加国内国际等会议的机会! 欢迎通过”快响计划“、”本博班”、或者”硕博连读“申请读博!实验室可提供自由选择课题等机会。 研究方向 名称 本实验室主要围绕抗体与临近诱导的化学生物学展开研究,具体主要包括如下三个方向: 1. 化学光遗传及光化学生物学。化学生物学是化学与生命科学的交叉,是许多重要生物技术突破的本源。获得诺奖的PCR技术的核心就是化学合成寡聚核苷酸取得成功,而近年来的酶的定向进化技术,以及生物正交化学反应也是化学技术与生物学理论交叉的代表性例案。本实验室在化学生物学领域主要围绕蛋白质的化学修饰和调控展开。我们首次提出了化学光遗传(chemo-optogentic)概念,发展了相比于传统光遗传技术具有更优越性能的光调控细胞的手段(2018)。我们将荧光探针与RPA技术结合,发展出了第一个基于RPA的恒温核酸检测技术并实现了单拷贝灵敏度地检测新冠病毒RNA,代表着新冠病毒检测的最高灵敏度(2020)。 2. 纳米抗体靶向蛋白降解。纳米抗体体积小(15kDa),稳定性高,容易原核表达和制备,具有良好的穿膜性,这些性质都是传统抗体(150kDa)所不具备的。本实验利用化学修饰的手段对纳米抗体进行修饰和功能化,赋予纳米抗体更多的特殊性能。我们将化学小分子技术与纳米抗体相结合,已经发展出了一系列的新技术,用于调控细胞的进程,靶向蛋白降解,乃至开发小分子纳米抗体偶联药物用于肿瘤的干预。例如开发出了SNACIP技术,首次实现了用小分子——纳米抗体来调控活细胞内部的靶标和信号通路,并用SNACIP工具首次调控了一个关键胞内肿瘤靶标TPX2,成功在小鼠体内有效抑制了肝癌肿瘤的增生(2022),而此前,无论是大分子抗体,还是小分子化合物,都对这种胞内的,无序的靶标无能为力,显示出这种偶联物的调控相比于传统的小分子或者大分子抗体的调控有很多不可取代的优势。我们实验室还着重发展与纳米抗体相关的靶向蛋白降解技术,可以实现对传统不可成药或者无配体结合位点的靶标进行降解,被认为是当前最前沿的药物开发策略。 3. 细胞骨架与肿瘤靶向。在细胞分裂过程中,细胞骨架(cytoskeleton)扮演着重要角色,例如决定细胞分裂的纺锤体主要是由微管细胞骨架(microtubules)构成。另一方面肿瘤细胞的侵袭和扩散与微丝细胞骨架(actin filaments)息息相关。我们用所发展出来的新技术,包括化学光遗传(chemo-optogenetics)等方法,以及纳米抗体技术,来研究与细胞骨架密切相关的生命科学难题。同时,我们目前关注的核心生物医学问题围绕着与细胞分裂密切相关的恶性肿瘤治疗展开。更具体一点,由微管细胞骨架构成的纺锤体是如何组装和被调控的,进而如何实现正确无误的细胞分裂过程,如何有效干预恶性肿瘤细胞的不受控分裂过程,进而特异性靶向相关通路,发展相应的抗体偶联物来抑制恶性肿瘤发生发展。 Publications Since 2019 名称 [12] Y. Zhou#, Y. Zhang#, C. Zhou, Z. Zhou, X. Chen*, Red light activatable chemo-optogenetic dimerization regulates cell apoptosis. Dye Pigm 2024, 223, 111973, 一区 (Jan. 26, 2024) [11] C. Zhou, H. He, X. Chen*, Photoactivatable nanobody conjugate dimerizer temporally resolves Tiam1-Rac1 signaling axis, Adv Sci 2024, 11(11), e2307549 [IF 15.1] (Jan. 15, 2024) [10] H. He#, C. Zhou#, X. Chen*, ATNC: versatile nanobody chimeras for autophagic degradation of intracellular unligandable and undruggable proteins. J. Am. Chem. Soc. 2023, 145(45), 24785-24795 [IF 15.0], cover story (Oct. 12, 2023) [9] Z. Zhou#, Y. Zhang#, S. Xia, X. Chen*, Red-light-activatable AND-gated antitumor immunosuppressant. Cells 2023, 12(19), 2351 (Sep. 26th, 2023) [8] X. Sun#, C. Zhou#, S. Xia#, X. Chen*, Small molecule-nanobody conjugate induced proximity controls intracellular processes and modulates endogenous unligandable targets. Nat. Commun. 2023, 14, 1635 [IF 16.6] (March 24, 2023) 【点评:(i)SNACIP解决了调控胞内无配体靶标的难题;(iii)直接调控内源靶标具有转化价值;(iii)解决了微管成核(Nature 1995)被发现以来近三十年未能发展出靶向微管成核而抑制肿瘤的药物这个难题。】 [7] 一种光激活的纳抗偶联物二聚化诱导剂 PANCID 及其应用。 China Invention Patent 2023 (ZL202211134314.1) [6] X. Chen*, S. Xia, Sensitive methods for detection of SARS-CoV-2 RNA ("Covid-19: Biomedical Perspectives"_Chapter 1) Methods Microbiol. 2022, 50, 1-26 (July 16, 2021) [专著丛书, Elsevier] [5] 一种小分子——纳米抗体偶联物临近效应的SNACIP诱导剂及其制备方法与应用。 China Invention Patent 2022 (ZL202210495991.X) [5] 一种用于检测新冠病毒SARS-CoV-2的探针和引物、试剂盒、检测方法及应用。 China Invention Patent 2021 (ZL202010358418.5) [4] D. Kamps, J. Koch, V. O. Juma, E. Campillo-Funollet, M. Graessl, S. Banerjee, T. Mazel, X. Chen, Y.-W. Wu, S. Portet, A. Madzvamuse, P. Nalbant, L. Dehmelt, Optogenetic tuning reveals Rho amplification-dependent dynamics of a cell contraction signal network Cell Rep. 2020, 33 (9), 108467 [IF 9.995] [3] S. Xia, X. Chen*, Single-copy sensitive, field-deployable and simultaneous dual-gene detection of SARS-CoV-2 RNA via modified RT-RPA Cell Discov. 2020, 6, 37 [IF 33.5] (May 28, 2020) 【点评:(i)首次基于RT-ERA/RPA检测新冠(2020年5月28日);(ii)首次将RT-RPA/ERA对RNA检测的灵敏度提高到单拷贝级别;(iii)建立了一套成熟流程WEPEAR,应对今后其它病毒疫情的爆发。】 [2] X. Chen, F. Li, Y.-W. Wu, Affinity conjugation for rapid and covalent labeling of proteins in live cells ("Proximity Labeling: Methods and Pprotocols"_Chapter 15) Methods Mol. Biol. 2019, Vol 2008, 191-202 [专著丛书, Springer Nature] [1] X. Chen*, S. Petry, Chemo-optogenetic control of cytoskeleton function. Abstr. Pap. Am. Chem. Soc. 2019, 258, 283 Publications Before 2019 名称 REPRESENTATIVE PUBLICATIONS: [1] X. Chen, M. Venkatachalapathy, L. Dehmelt, Y.-W. Wu*, Multidirectional activity control of cellular processes by a versatile chemo-optogenetic approach (Very Important Paper) Angew. Chem. Int. Ed. 2018, 57(37), 11993-11997 [IF 16.6] (July 26, 2018) [This work was reported, or press released by over 20 media or organizations, including ChemistryViews, Science Daily, Wiley, etc. in English, Chinese and Swedish] [2] X. Chen, Y.-W. Wu*, Tunable and photoswitchable chemically induced dimerization for chemo-optogenetic control of protein and organelle positioning Angew. Chem. Int. Ed. 2018, 57(23), 6796-6799 [IF 16.6] (April 10, 2018) [This technique was patented; highlighted in X-MOL] [3] X. Chen#, M. Venkatachalapathy#, D. Kamps, S. Weigel, R. Kumar, M. Orlich, R. Garrecht, M. Hirtz, C. M. Niemeyer, Y.-W. Wu*, Leif Dehmelt*, “Molecular Activity Painting”: Switch-like, light-controlled perturbations inside living cells (Hot Paper/Cover Story; #: co-first author) Angew. Chem. Int. Ed. 2017, 56(27), 5916-5920 [IF 16.6] (Mar 29, 2017) [“Molecular activity painting” work was press released by Wiley and Max Planck Society, and reported by PNOK, X-MOL, AdvancedScienceNews, etc. in different languages] [4] W. Liu#, F. Li#, X. Chen#, J. Hou#, L. Yi, Y.-W. Wu*, A rapid and fluorogenic TMP-AcBOPDIPY probe for covalent labeling of proteins in live cells (#: co-first author) J. Am Chem. Soc. 2014, 136(12), 4468-71 [IF 16.6] (Mar 5, 2014) [This work was highlighted in Chem. Soc. Rev. 2015] [5] X. Chen, F. Li, Y.-W. Wu*, Chemical labeling of intracellular proteins via affinity conjugation and strain-promoted cycloadditions in live cells Chem. Commun. 2015, 51, 16537-16540 (Sep 18, 2015) [This work was highlighted in Curr. Opin. Biotechnol. 2017] OTHER FIRST AUTHOR PAPERS: [6] X. Chen, Y.-W. Wu, Selective chemical labeling of proteins Org. Biomol. Chem. 2016, 14, 5417-5439 [Selected as “Of Outstanding Interest” by peer scientists in Curr. Opin. Biotechnol. 2017] [7] X. Chen, L. Henschke, Q. Wu, B. Neumann, K. Muthoosamy, T. Weil, Site-selective azide incorporation into endogenous RNase A via a "chemistry" approach Org. Biomol. Chem. 2013, 11, 353-61 [8] X. Chen, K. Muthoosamy, A. Pfisterer, B. Neumann, T. Weil, Site-selective lysine modification of native proteins and peptides via kinetically controlled labeling Bioconjugate Chem. 2012, 23, 500-508 [This work was highlighted in Chem. Rev. 2015] [9] X. Chen, Q. Wu, L. Henschke, G. Weber, T. Weil, An efficient and versatile approach for the preparation of a rhodamine B ester bioprobe library Dyes Pigm. 2012, 94, 296-3038 [10] X. Chen, A. Pfisterer, K. Müllen, T. Weil, Site-directed protein and peptide chemistry via tailored bioorthogonal reagents Abstr. Pap. Am. Chem. Soc. 2011, 241, 681-ORGN CO-AUTHORED PAPERS: [11] B. K. Agrawalla, T. Wang, A. Riegger, M. Domogalla, K. Steinbrink, T. D?rfler, X. Chen, F. Boldt, M. Lamla, J. Michaelis, S. L. Kuan, T. Weil, Chemoselective dual and triple labelling of native and recombinant proteins Bioconjugate Chem. 2018, 29, 29-34 [12] P. Liu, A. Calderon, G. Konstantinidis, J. Hou, S. Voss, X. Chen, F. Li , S. Banerjee, J.-E. Hoffmann, C. Theiss, L. Dehmelt, Y.-W. Wu, A bioorthogonal small-molecule switch system for controlling protein function in cells Angew. Chem. Int. Ed. 2014, 53, 10049-10055 [13] S. Voss, L. Zhao, X. Chen, F. Gerhard, Y.-W. Wu, Generation of an intramolecular three-color FRET probe by site-specific protein labeling J. Pept. Sci. 2013, 20, 115-120 [14] M. Lillich, X. Chen, T. Weil, H. Barth, J. Fahrer, Streptavidin-conjugated C3 protein mediates the delivery of mono-biotinylated RNase A into macrophases Bioconjugate Chem. 2012, 23, 1426-1436 [15] M. Lillich, X. Chen, T. Weil, H. Barth, J. Fahrer, Delivery of mono-biotinylated RNaseA into macrophages with streptavidin-conjugated Clostridium botulinum C3 toxin N.-S. Arch. Pharmacol. 2012, 385 (1), 53 [16] A. Pfisterer, K. Eisele, X. Chen, M. Wagner, K. Müllen, T. Weil, Bioactive unnatural somatostatin analogues through bioorthogonal iodo and ethynyl-disulfide intercalators Chem. Eur. J. 2011, 17, 9697-9707 论著 名称 [17] X. Chen, S. Voss, Y.-W. Wu, Chemoselective modification of proteins (Chapter 8) Wiley-VCH (“Chemical ligation: Tools for biomolecule synthesis and modification”) 2017, 285-338 专利 名称 [18] Y.-W. Wu, X. Chen, Photo-switchable chemical inducers of dimerization for control of protein functions in cells by light as European Patent: Patent No. EP3424922A1, published on January 9th, 2019 as PCT Patent: Patent No. WO2019008175, published on January 10th, 2019 本实验室掠影 title 1. 主实验室 2. 本实验室 细胞培养间 3. 本实验室 共聚焦及TIFR激光显微镜间 4. 本实验室 蛋白纯化冷室 5. 本实验室 有机化学合成平台 6. 本实验室 爪蟾模式动物间 & 昆虫表达系统平台 除了本实验室的设备、仪器、平台之外,还有生命科学中心的各大仪器平台(高分辨质谱、流式细胞仪、高速及超速离心机等)、生命科学与技术学院仪器平台(600MHz核磁共振、ITC、冷冻电镜等)、大科学实验平台(超分辨显微镜、双光子显微镜等)做支撑,科研仪器设备支撑体系相当完备。 Lab Members 名称 CHEN, Xi: Principal Investigator XIA, Simin SUN, Xiaofeng ZHOU, Chengjian WU, Donglian HE, Huiping ZHANG, Yan XI, Ruyu GENG, Yiqing SONG, Haole JIANG, Shoujin (joint program) ALUMNI: MAO, Haoyu TU, Mingyue ZHOU, Yue XIAO, Yang LI, Siyang ZHOU, Ziqi DAI, Qiuyang Group photo 名称 Lab updates 名称 2024-04-07: Our team is invited by X-MOL to contribute a post summarizing the recent research progress of our group. Congratulations to everyone who were involved in these works! X-MOL报道 哈尔滨工业大学陈西课题组 近年工作概览:纳米抗体及临近诱导的化学生物学(2024.4.7) https://www.x-mol.com/news/884160 2024-03-04: Welcome bachelor student Haole Song join our group! 2024-01-15: Our first representative chemo-optogenetic (化学光遗传) paper entitled "Photoactivatable nanobody conjugate dimerizer temporally dissects Tiam1-Rac1 signaling axis" is now published online in Advanced Science, and is being considered as a cover in an issue. Congratulations to Ph.D. student Chengjian Zhou and other co-authors! 2023-12-28: We got a happy eve for New Year Celebration! 2023-11-20: Welcome student Yiqing Geng join our group! 2023-10-30: Congratulations to Master student Yan Zhang who was awarded the "National Scholarship 国家奖学金" for gradulate student! 2023-10-29: Our paper about ATNC 自噬靶向纳米抗体嵌合体 technology published in JACS was reported by several scentific media including X-MOL, CBG, HIT media, and etc.! Now this technology is known by the chemical biology and biomedical fields. 2023-09-23: Our paper titled 'Red light activatable AND-gated antitumor immunosuppressant' has now been accepted for publication in the journal Cells. Congratulations to Ziqi, Yan, and other coauthors! 2023-09-22:As the guest editor of Bioengineering (IF 4.6), we have officially lanched the special issue entitled "Nanobody-based targeted protein degradation". The deadline for submission is May 15th, 2024. Contributions are coordinately invited! The following is the description link homepage Website: https://www.mdpi.com/journal/bioengineering/special_issues/E5JC6PAE00 2023-09-17:The term 化学光遗传(chemo-optogenetics)is now officially coined in Baidubaike. The following is the link: 化学光遗传_百度百科 (baidu.com) 2023-09-16:We have a great excursion at the Maoer Mountain. 2023-09-15:Congratulations to Donglian for successfully passing her frist Ph.D. general evaluation! 2023-09-14:Our research paper titled "ATNC: Versatile nanobody chimeras for autophagic degradation of intracellular unligandable and undruggable proteins" has been accepted for publication in Journal of the American Chemical Society, and has been selected as Front Covery story. Congratulations to Huiping and Chengjian who are co-first authors! 2023-09-10:Prof. CHEN delivered a speech about“Chemically induced proximity regulates cell division” in The 4th National Annual Conference on Cancer Cell Biology! 2023-09-6:We got two papers finished and published on ChemRixv as preprints. Feel free to access and download! 2023-08-17:Prof. CHEN delivered a speech about "New-generation induced proximity systems regualte cytoskeleton function” in The 3rd China Frionter Cytoskeleton Symposium (Chinese Society for Cell Biology) ! 2023-07-12: We have a great group dinner and enjoyed Russian style barbecue ! 2023-07-11: Welcome undergraduate summer camp students to visit our laboratory! 2023-07-04:Welcome Prof. Xuechen Li from Hongkong University visit our laboratory! 2023-07-03: Welcome students from the International Student Summer Camp to visit our laboratory! 2023-06-20:Prof. CHEN delivered a speech about Chemically Induced Proximity in CCS (Chinese Chemical Society) annual meeting! 2023-05-23: We have a great group dinner and much enjoyed Dongbei Food! 2023-05-23: Congratulations to Huiping, Ziqi and Qiuyang for passing their M.Sc. degree defenses! 2023-04-26: Principal Investigator Prof. CHEN delivered a speech in the 9th Life Science Salon in School of Life Science and Technology! 2023-03-31: Our SNACIP paper published in Nature Communications received many invitations from different scientific media across Chemistry and Biotechnology fields for contributing news reports to describe our findings! 2023-03-08: Our paper regarding SNACIP technology was officially accepted by Nature Communications, and got an invitation for contributing a Featured Art! Congratulations to Xiaofeng, Chengjian, and Simin who are co-first authors! 2022-08-19: Welcome Siyang join our group. 2022-06-30: Congratulations to Donglian and Yue for passing their M.Sc. degree defenses! 2022-06-01: Our group opened a Public Account in WeChat: "陈西课题组点评"。Welcome to follow. 2022-01-24: We got a nice group dinner and enjoyed our evening activities! 2021-11-29: Welcome student Ruyu join our group! 2021-11-12: Congratulations to Donglian for passing her Ph.D. interview! 2021-10-1: Welcome rotation student Mingyue join our group! 2021-9-01:Welcome new graduate students join our group! 2021-07-23: We attended the "The 5th Asia-Pacific Joint Symposium on Life Sciences". 2021-07-16: Our book series chapter Sensitive methods for detection of SARS-CoV-2 RNA is online now. 2021-07-01: Congratulations to Xiaofeng and Chengjian for passing their Ph.D. interview! 2020-12-29: Our first group dinner goes so well! 2020-05-28: 课题组新冠抗疫项目的论文“Single-copy sensitive, field-deployable, and simultaneous dual-gene detection of SARS-CoV-2 RNA via modified RT–RPA”在Cell Discovery杂志上正式上线发表!文章被遴选为致编辑的信Correspondence,全文链接如下: https://rdcu.be/b4rKe 该论文首次通过核酸恒温扩增技术实现对新冠病毒的单拷贝灵敏度现场检测。 2020-03-23:课题组文章“Ultrasensitive and whole-course encapsulated field detection of 2019-nCoV gene applying exponential amplification from RNA combined with chemical probes” 在ChemRxiv 上线发表。

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