个人简介

本科及博士就读于同济大学生命科学与技术学院生物信息学专业，2012年获得学士学位，2017年获得博士学位。2017-2018年在同济大学生物医学工程博士后流动站从事博士后研究。2018-2020年在美国哈佛大学Dana-Farber癌症研究所从事博士后研究。2020年受聘于同济大学生命科学与技术学院任特聘研究员，2023年任教授。主持多个国家级科研项目，包括国家自然科学基金优青项目、面上项目、青年基金等。获得吴瑞奖学金、博士后创新人才支持计划、上海市科技启明星、同济大学追求卓越奖荣誉支持。担任Nature Methods、Nature Communications、Genome Biology、NAR、Cell Systems、Cell Genomics等领域内杂志独立审稿人。

研究领域

一、单细胞及空间多组学生物信息学方法开发 单细胞空间多组学对于理解复杂生物系统异质性具有重要意义，然而目前领域内缺乏有效的整合分析方法。课题组开发了一系列的机器学习及深度学习方法，系统解决单细胞空间多组学整合分析问题。主要成果包括单细胞转录组学与表观遗传组学整合分析方法MAESTRO（Genome Biology 2020）。基于主题模型的空间转录组学精度提升算法STRIDE（Nucleic Acids Research 2022）。整合单细胞染色质开放数据及海量公共数据集的转录调控网络预测算法SCRIP（Nucleic Acids Research 2022）。单细胞CRISPR筛选数据分析流程SCREE（Briefings in Bioinformatics 2023）等。 二、表观遗传及代谢重编程对细胞身份转变的调控机制 细胞身份转变在发育、免疫、衰老等生物学过程中均发挥了重要的作用。课题组致力于开发新的单细胞、空间多组学测序及扰动技术，结合人工智能方法和海量数据整合，研究表观遗传内因和代谢环境外因对细胞身份转变的调控机制。主要成果包括在哺乳动物早期胚胎发育的过程中，研究了组蛋白修饰H3K4me3、H3K27me3（Nature 2016）、H3K9me3（Nature Cell Biology 2018、Cell Stem Cell 2022），以及核小体定位（Cell Research 2022）等表观修饰对细胞命运决定的调控作用。Nature工作被评选为2016年中国生命科学领域十大进展。同时，基于表观修饰如DNA甲基化（Cell Stem Cell 2018）、组蛋白修饰（Cell Discovery 2016）的调节可以有效促进体细胞重编程过程中的细胞命运决定，提高重编程胚胎发育率。 三、细胞状态转变在肿瘤免疫、发育及衰老相关疾病中的调控及作用 在对细胞命运表观及代谢调控深入理解的基础上，课题组拟基于不同生物系统高通量、多维度的单细胞时空数据，利用人工智能方法，总结细胞身份转变的普适规律并建立量化模型，系统探讨细胞身份转变对相关疾病的调控作用，发掘关键细胞类型，探索调控机制并鉴定潜在药物靶点。主要成果包括建立单细胞肿瘤免疫微环境基因表达图谱TISCH（Nucleic Acids Research 2021，2023），人类单细胞器官基因表达图谱HUSCH（Nucleic Acids Research 2023）, 开发了基于人工智能的单细胞细胞类型注释算法SELINA（bioRxiv 2022），揭示了肿瘤细胞对INF-g的耐受机制（Cancer Immunology Research 2023）等。

生物信息学

近期论文

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Ren P#, Shi X#, Dong X, Yu Z, Ding X, Wang J, Sun L, Yan Y, Hu J, Zhang P, Chen Q, Li T, Wang C*. SELINA: Single-cell Assignment using Multiple-Adversarial Domain Adaptation Network with Large-scale References. Cell Rep. Methods 2023; 100577. Wei H#, Han T, Li T, Wu Q*, Wang C*. SCREE: a comprehensive pipeline for single-cell multi-modal CRISPR screen data processing and analysis. Brief. Bioinformatics 2023; 24(3),bbad123. Han Y#, Wang Y#, Dong X#, Sun D, Liu Z, Yue J, Wang H, Li T*, Wang C*. TISCH2: expanded datasets and new tools for single-cell transcriptome analyses of the tumor microenvironment. Nucleic Acids Res. 2023; 51(D1),D1425-D1431. Shi X#, Yu Z#, Ren P, Dong X, Ding X, Song J, Zhang J, Li T*, Wang C*. HUSCH: an integrated single-cell transcriptome atlas for human tissue gene expression visualization and analyses. Nucleic Acids Res. 2023; 51(D1),D1029-D1037. Han T#, Wang X#, Shi S, Zhang W, Wang J, Wu Q, Li Z, Fu J, Zheng R, Zhang J, Tang Q, Zhang P*, Wang C*. Cancer Cell Resistance to IFNγ Can Occur via Enhanced Double-Strand Break Repair Pathway Activity. Cancer Immunol Res. 2023; 11(3),381–398. Hu J#, Zhang L#, Xia H#, Yan Y#, Zhu X, Sun F, Sun L, Li S, Li D, Wang J, Han Y, Zhang J, Bian D, Yu H, Chen Y, Fan P, Ma Q, Jiang G, Wang C*, Zhang P*. Tumor microenvironment remodeling after neoadjuvant immunotherapy in non-small cell lung cancer revealed by single-cell RNA sequencing. Genome Med. 2023; 15(1),1-14. Cao G#, Yue J#, Ruan Y#, Han Y, Zhi Y, Lu J, Liu M, Xu X, Wang J, Gu Q, Wen X, Gao J, Kang J, Zhang Q, Wang C*, Li F*. Single-cell Dissection of Cervical Cancer Reveals Key Subsets of the Tumor Immune Microenvironment. EMBO J. 2023; 42,e110757. Sahu A#*, Wang X#, Munson P#, Klomp J, Wang X, Gu S, Han Y, Qian G, Nicol P, Zeng Z, Wang C, Tokheim C, Zhang W, Fu J, Wang J, Nair N, Rens J, Bourajjaj M, Jansen B, Leenders I, Lemmers J, Musters M, Zanten S, Zelst L, Worthington J, Liu J, Juric D, Meyer C, Oubrie A, Liu X, Fisher D*, Flaherty K*. Discovery of Targets for Immune–Metabolic Antitumor Drugs Identifies Estrogen-Related Receptor Alpha. Cancer Discov. 2023; 13(3),672-701. Zhang Y, Xiang G, Jiang AY, Lynch A, Zeng Z, Wang C, Zhang W, Fan J, Kang J, Gu S, Wan C, Zhang B, Liu XS*, Brown M*, Meyer CA*. MetaTiME integrates single-cell gene expression to characterize the meta-components of the tumor immune microenvironment. Nat. Commun. 2023; 14(1),2634. Sun D#, Liu Z, Li T, Wu Q*, Wang C*. STRIDE: accurately decomposing and integrating spatial transcriptomics using single-cell RNA sequencing. Nucleic Acids Res. 2022; 50(7),e42-e42. Dong X#, Tang K#, Xu Y, Wei H, Han T, Wang C*. Single-cell Gene Regulation Network Inference by Large-scale Data Integration. Nucleic Acids Res. 2022; 50(21),e126-e126. Liu Z#, Sun D, Wang C*. Evaluation of cell-cell interaction methods by integrating single-cell RNA sequencing data with spatial information. Genome Biol. 2022; 23(1),1-38. Xu R#, Li S#, Wu Q#, Li C#, Jiang M#, Guo L, Chen M, Yang L, Dong X, Wang H, Wang C*, Liu X*, Ou X*, Gao S*. Stage-specific H3K9me3 occupancy ensures retrotransposon silencing in human preimplantation embryos. Cell Stem Cell 2022; 29(7),1051-1066. Cover Story Wang C#, Chen C#, Liu X#, Li C#, Wu Q, Chen X, Yang L, Kou X, Zhao Y, Wang H, Gao Y*, Zhang Y*, Gao S*. Dynamic nucleosome organization after fertilization reveals regulatory factors for mouse zygotic genome activation. Cell Res. 2022; 32(9),801-813. Cover Story Yang H#, Bai D#, Li Y#, Yu Z#, Wang C, Sheng Y, Liu W*, Gao S*, Zhang Y*. Allele-specific H3K9me3 and DNA methylation co-marked CpG-rich regions serve as potential imprinting control regions in pre-implantation embryo. Nat. Cell Biol. 2022; 24(5),783-792. Zheng W#*, Wang X#*, Liu J, Yu X, Li L, Wang H, Yu J, Pei X, Li C, Wang Z, Zhang M, Zeng X, Zhang F, Wang C, Chen H, Chen H*. Single-cell analyses highlight the proinflammatory contribution of C1q-high monocytes to Beh?et’s disease. PNAS 2022; 19(26),e2204289119. Sun D#, Wang J#, Han Y#, Dong X, Zheng R, Ge J, Shi X, Wang B, Ren P, Sun L, Yan Y, Zhang P, Zhang F*, Li T*, Wang C*. TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment. Nucleic Acids Res. 2021; 49(D1),D1420-D1430. Zhang H#, Song L#, Wang X, Cheng H, Wang C, Meyer CA, Liu T, Tang M, Aluru S, Yue F, Liu XS*, Li H*. Fast alignment and preprocessing of chromatin profiles with Chromap. Nat. Commun. 2021; 12(1),6566. Wu SZ#, Al-Eryani G#, Roden DL#, Junankar S, Harvey K, Andersson A, Thennavan A, Wang C, Torpy JR, Bartonicek N, Wang T, Larsson L, Kaczorowski D, Weisenfeld NI, Uytingco CR, Chew JG, Bent ZW, Chan C, Gnanasambandapillai V, Dutertre CA, Gluch L, Hui M, Beith J, Parker A, Robbins E, Segara D, Cooper C, Mak C, Chan B, Warrier S, Ginhoux F, Millar E, Powell JE, Williams TR,Liu XS, O’Toole S, Lim E, Lundeberg J, Perou CM, Swarbrick A*. A single-cell and spatially resolved atlas of human breast cancers. Nat. Genet. 2021; 53(9),1334-1347. Wang C#, Sun D#, Huang X, Wan C, Li Z, Han Y, Qin Q, Fan J, Qiu X, Xie Y, Meyer CA, Brown M, Tang M, Long H, Liu T*, Liu XS*. Integrative analyses of single-cell transcriptome and regulome using MAESTRO. Genome Biol. 2020; 21(1),1-28. Burton A, Brochard V, Galan C, Ruiz-Morales E, Rovira Q, Rodriguez-Terrones D, Kruse K, Gras S, Udayakumar V, Chin H, Eid A, Liu X, Wang C, Gao S, Pradhan S, Vaquerizas J, Beaujean N, Jenuwein T, Torres-Padilla M. Heterochromatin establishment during early mammalian development is regulated by pericentromeric RNA and characterized by non-repressive H3K9me3. Nat. Cell Biol. 2020; 22(7),767-778. Wu SZ#, Roden D#, Wang C, Holliday H, Harvery K, Cazet AS, Murphy KJ, Pereira B, Al-Eryani G, Bartonicek N, Hou R, Torpy JR, Junankar S, Chan C, Lam CE, Hui M, Gluch L, Beith J, Parker A, Robbins E, Segara D, Mark C, Cooper C, Warrier S, Forrest A, Powell J, O’Toole S, Cox TR, Timpson P, Lim E, Liu XS, Swarbrick A*. Stromal cell diversity associated with immune evasion in human triple-negative breast cancer. EMBO J. 2020; 39(19),e104063. Gu S#, Wang X#, Hu X#, Jiang P, Li Z, Traugh N, Bu X, Tang Q, Wang C, Zeng Z, Fu J, Meyer C, Zhang Y, Cejas P, Lim K, Wang J, Zhang W, Tokheim C, Sahu AD, Xing X, Kroger B, Ouyang Z, Long H, Freeman GJ*, Brown M*, Liu XS*. Clonal tracing reveals diverse patterns of response to immune checkpoint blockade. Genome Biol. 2020; 21,263. 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Identification of key factors conquering developmental arrest of somatic cell cloned embryos by combining embryo biopsy and single-cell sequencing. Cell Discov. 2016; 2(1),1-15. Gao R#, Xiu W#, Zhang L, Zang R, Yang L, Wang C, Wang M, Wang M, Yi L, Tang Y, Gao Y, Wang H, Xi J, Liu W, Wang Y, Wen X, Yu Y, Zhang Y, Chen L, Chen J*, Gao S*. Direct induction of neural progenitor cells transiently passes through a partially reprogrammed state. Biomaterials 2017; 119,53-67. Xu K#, Chen X#, Yang H, Xu Y, He Y, Wang C, Huang H, Liu B, Liu W, Li J, Kou X, Zhao Y, Zhao K, Zhang L, Hou Z, Wang H, Wang H, Li J, Fan H, Wang F, Gao Y, Zhang Y, Chen J*, Gao S*. Maternal Sall4 is indispensable for epigenetic maturation of mouse oocytes. J. Biol. Chem. 2017; 292,1798-1807. Wang Y, Wu Q, Yang P, Wang C, Liu J, Ding W, Liu W, Bai Y, Yang Y, Wang H, Gao S*, Wang X*. LSD1 co-repressor Rcor2 orchestrates neurogenesis in the developing mouse brain. Nat. Commun. 2016; 7,10481. 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