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张泽民

邮  箱: zemin@pku.edu.cn

职  称:教授

办公室地址:北京市海淀区颐和园路5号,综合科研2号楼,100871

所属实验室:张泽民实验室,生物动态光学成像中心(BIOPIC),生命科学联合中心

个人主页:http://cancer-pku.cn/

  • 个人简介
  • 代表性论文
  • 实验室简介

个人介绍:

张泽民,北京大学生物医学前沿创新中心研究员、副主任,北京大学未来基因诊断高精尖创新中心研究员,中国“海外高层次人才”计划,长江特聘教授,北大-清华生命科学联合中心高级研究员。 1988年本科毕业于南开大学生物系, 1989年由 CUSBEA 项目赴美留学。1995年研究生毕业于宾州州立大学生物化学和分子生物学专业, 获得博士学位 ;1995-1998年在美国旧金山加州大学进行博士后研究工作。1998年起任职于美国 GENENTECH 公司开始生物信息学研究, 曾任博士后导师, 生物信息学部主任, 生物信息首席科学家。前期主要工作包括: 在世界上首次报道实体癌的全基因组测序; 首次在全基因组水平研究病毒插入事件在肝癌发生发展中的作用; 首次通过计算方法鉴别癌症的驱动突变。通过对癌症高通量数据的分析, 成功地发现了多种特异性抗癌靶点, 获得60多项美国专利授权。2014 年加入北京大学。2017年获The Boehringer Ingelheim Investigator Award,2017年获Bayer Investigator Award, 相关成果入选2017年度中国十大医学科技新闻、2017年度中国生命科学十大进展、细胞出版社2017和2019中国年度论文、2018和2019年度中国生物信息十大进展、2020年细胞杂志最佳论文。
1. S. Cheng, Z. Li, R. Gao, B. Xing, Y. Gao, Y. Yang, S. Qin, L. Zhang, H. Ouyang, P. Du, L. Jiang, B. Zhang, Y. Yang, X. Wang, X. Ren, J. Bei, X. Hu, Z. Bu*, J. Ji*, and Z Zhang*. (2021) A pan-cancer single-cell transcriptional atlas of tumor infiltrating myeloid cells. Cell, 184:792-809

2. L. Zheng and Z. Zhang*. (2021) Decoding the genetic basis of anti-tumor immunity. Immunity, 54:199-201,

3. X. Ren, W. Wen, X. Fan, W. Hou, B. Su, P.i Cai, J. Li, Y. Liu, F. Tang, F. Zhang, Y. Yang, J. He, W. Ma, J. He, P. Wang, … P. Zhou*, Q. Jiang*, Z. Huang*, J-X Bei*, L. Wei*, X-W Bian*, X. Liu*, T Cheng*, X. Li*, P. Zhao*, F-S Wang*, H. Wang*, B. Su*, Z. Zhang*, K. Qu*, X. Wang*, J. Chen*, R. Jin*, Z. Zhang*, (2021) COVID-19 immune features revealed by a large-scale single cell transcriptome atlas, Cell, https://doi.org/10.1016/j.cell.2021.01.053

4. B. Liu, C. Li, Z. Li, D. Wang, X. Ren, and Z. Zhang*. (2020) An entropy-based metric for assessing the purity of single cell populations, Nature Communications, 11:3155

5. X. Ren*, G. Zhong, Q. Zhang, L. Zhang, Y. Sun and Z. Zhang*. (2020) Reconstruction of cell spatial organization from single-cell RNA sequencing data based on ligand-receptor mediated self-assembly, Cell Research, 30:763-778

6. Q. Zhang and Z. Zhang. (2020) Stepwise immune alterations in multiple myeloma progression. Nature Cancer, 1:477-479

7. L. Zhang, Z. Li, K. M. Skrzypczynska, Q. Fang, W. Zhang, S. A. O’Brien, Y. He, L. Wang, Q. Zhang, A. Kim, R. Gao, J. Orf, T. Wang, D. Sawant, J. Kang, D. Bhatt, D. Lu, C-M Li, A. Rapaport, K. Perez, Y. Ye, S. Wang, X. Hu, X. Ren, W. Ouyang, Z. Shen*, J. G. Egen*, Z Zhang*, and X. Yu*. (2020) Single-cell analyses inform mechanisms of myeloid-targeted therapies in colon cancer. Cell, 181:442-459

8. C. Li, B. Liu, B. Kang, Z. Liu, Y. Liu, C. Chen, X. Ren*, and Z. Zhang*. (2020) SciBet as a portable and fast single cell type identifier. Nature Communications, 11:1818

9. PCAWG Transcriptome Core Group, C. Calabrese, N. R. Davidson, D. Demircioğlu, N. A. Fonseca, Y. He, A. Kahles, K-V Lehmann, F. Liu, Y. Shiraishi, C. M. Soulette, L. Urban, L. Greger, S. Li, D. Liu, M. D. Perry, Q. Xiang, F. Zhang, J. Zhang, P. Bailey, S. Erkek, K. A. Hoadley, Y. Hou, M. R. Huska, H. Kilpinen, J. O. Korbel, M. G. Marin, J. Markowski, T. Nandi, Q. Pan-Hammarström, C. S. Pedamallu, R. Siebert, S. G. Stark, H. Su, P. Tan, S. M. Waszak, C. Yung, S. Zhu, P. Awadalla, C. J. Creighton, M. Meyerson, B. F. Ouellette, K. Wu, H. Yang, PCAWG Transcriptome Working Group, A. Brazma*, A. N. Brooks*, J. Göke*, G. Rätsch*, R. F. Schwarz*, O. Stegle*, Z. Zhang* & PCAWG Consortium. (2020) Genomic basis for RNA alterations in cancer. Nature, 578:129-136

10. The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium. (2020) Pan-cancer analysis of whole genomes. Nature, 578:82–93

11. Y. Zhang, F. Chen, N. A. Fonseca, Y. He, M. Fujita, H. Nakagawa, Z. Zhang, A. Brazma; PCAWG Transcriptome Working Group; PCAWG Structural Variation Working Group, C. J. Creighton; PCAWG Consortium. (2020) High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations. Nature Communications, 11:736

12. R. Bernards, E. Jaffee, J. A. Joyce, S. W. Lowe, E. R. Mardis, S. J. Morrison, K. Polyak, C. L. Sears, K. H. Vousden, and Z. Zhang. (2020) A roadmap for the next decade in cancer research. Nature Cancer, 1:12-17

13. R. Yang, S. Cheng, N. Luo, R. Gao, K. Yu, B. Kang, L. Wang, Q. Zhang, Q. Fang, L. Zhang, C. Li, A. He, X. Hu, J. Peng*, X. Ren*, and Z. Zhang*. (2020) Distinct epigenetic features of tumor-reactive CD8+ T cells in colorectal cancer patients revealed by genome-wide DNA methylation analysis. Genome Biology, 21:2

14. Y. Zhang and Z. Zhang*. (2020) The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cellular & Molecular Immunology, 17(8):807-821

15. F. Liu, Y. Zhang, L. Zhang, Z. Li, Q. Fang, R. Gao, and Z. Zhang. (2019) Systematic comparative analysis of single-nucleotide variant detection methods from single-cell RNA sequencing data. Genome Biology, 20:242

16. Q. Zhang, Y. He, N. Luo, S. J. Patel, Y. Han, R. Gao, M. Modak, S. Carotta, C. Haslinger, D. Kind, G. W. Peet, G. Zhong, S. Lu, W. Zhu, Y. Mao, M. Xiao, M. Bergmann, X. Hu, S. P. Kerkar, A. B. Vogt, S. Pflanz, K. Liu*, J. Peng*, X. Ren*, and Z. Zhang* (2019) Landscape and dynamics of single immune cells in hepatocellular carcinoma. Cell, 179:829-845.

17. H. Yang, L. Xia, J. Chen, S. Zhang, V. Martin, Q. Li, S. Lin, J. Chen, J. Calmette, M. Lu, L. Fu, J. Yang, Z. Pan, K. Yu, J. He, E.Morand, G. Schlecht-Louf, R. Krzysiek, L. Zitvogel, B. Kang, Z. Zhang, A. Leader, P. Zhou, L. Lanfumey, M. Shi, G. Kroemer, and Y. Ma. (2019) Stress–glucocorticoid–TSC22D3 axis compromises therapy-induced antitumor immunity. Nature Medicine, 26:1428-1441.

18. R. Xu, S. Yu, D. Zhu, X. Huang, Y. Xu, Y. Lao, Y. Tian, J. Zhang, Z. Tang, Z. Zhang, J. Yi, H. Zhu, and X. Zheng. (2019) hCINAP regulates the DNA-damage response and mediates the resistance of acute myelocytic leukemia cells to therapy. Nature Communications, 10: 3812.

19. Z. Tang, B. Kang, C. Li, T. Chen, and Z. Zhang. (2019) GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Research, 47:W556-W560

20. L. Zhang and Z. Zhang. (2019) Recharacterizing tumor-infiltrating lymphocytes by single-cell RNA sequencing. Cancer Immunology Research, 7:1040-1046.

21. L. Zhang, X. Yu, L. Zheng, Y. Zhang, Y. Li, Q. Fang, R. Gao, B. Kang, Q. Zhang, J.Y. Huang, H. Konno, X. Guo, Y. Ye, S. Gao, S. Wang, X. Hu, X. Ren, Z. Shen*, W. Ouyang*, and Z. Zhang*. (2018) Lineage tracking reveals dynamic relationships of T cells in colorectal cancer. Nature, 564:268-272

22. X. Guo, Y. Zhang, L. Zheng, C. Zheng, J. Song, Q. Zhang, B. Kang, Z. Liu, L. Jin,R. Xing, R. Gao, L. Zhang, M. Dong, X. Hu, X. Ren, D. Kirchhoff, H. G. Roider, T. Yan*, and Z. Zhang*. (2018) Global characterization of T cells in non-small cell lung cancer by single-cell sequencing. Nature Medicine, 24:978-985

23. X. Ren*, B. Kang, and Z. Zhang*. (2018) Understanding tumor ecosystems by single-cell sequencing: promises and limitations. Genome Biology, 19:211

24. C. Zheng, L. Zheng, J.-K. Yoo, H. Guo, Y. Zhang, X. Guo, B. Kang, R. Hu, J. Y. Huang, Q. Zhang, Z. Liu, M. Dong, X. Hu, W. Ouyang*, J. Peng*, and Z. Zhang*. (2017) Landscape of infiltrating T cells in liver cancer revealed by single-cell sequencing. Cell, 169(7), 1342–1356

25. Z. Tang, C. Li, B. Kang, G. Gao, C. Li, and Z. Zhang. (2017) GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Research, 45(W1):W98-W102

26. X. Hu and Z. Zhang. (2016) Understanding the genetic mechanisms of cancer drug resistance using genomic approaches. Trends in Genetics, 32(2):127-37

27. C. Klijn, S. Durinck, E. Stawiski, P. M. Haverty, Z. Jiang, H. Liu, J. Degenhardt, O. Mayba, F. Gnad, J. Liu, G. Pau, J. Reeder, Y. Cao, K. Mukhyala, S. K. Selvaraj, M. Yu, G. J. Zynda, M. J. Brauer, T. D. Wu, R. C. Gentleman, G. Manning, R. L. Yauch, R. Bourgon, D. Stokoe, Z. Modrusan, R. M. Neve, F. J. de Sauvage, J. Settleman*, S. Seshagiri*, and Z. Zhang* (2015) A comprehensive transcriptional portrait of human cancer cell lines. Nature Biotechnology, 33:305-315

28. S. Jhunjhunwala, Z. Jiang, E. W. Stawiski, F. Gnad, J. Liu, O. Mayba, P. Du, J. Diao, C. Santos, K-F Wong, Z. Gao, Y. Li, S. Johnson, H. M. Stern, T. D. Wu, S. B. Kapadia, Z. Modrusan, J. M. Luk, D. M. French, S. Seshagiri, and Z. Zhang (2014) Diverse modes of genomic alterations in hepatocellular carcinoma. Genome Biology, 15:436

29. J. Liu, M. McCleland, E. Stawiski, F. Gnad, P. M. Haverty, S. Durinck, Y-J. Chen, C. Klijn, O. Mayba, S. Jhunjhunwala, M. Lawrence, H. Liu, Y. Wan, V. Chopra, W. Yuan, C. Ha, H. Gilbert, J. Reeder, G. Pau, J. Stinson, H. Stern, G. Manning, T. D. Wu, R. Neve, F. J. de Sauvage, Z. Modrusan, S. Seshagiri, R. Firestein, and Z. Zhang (2014), Integrated exome and transcriptome sequencing reveals ZAK isoform usage in gastric cancer. Nature Communications, 5:3830

30. O. Mayba, H. N. Gilbert, J. Liu, P. M. Haverty, S. Jhunjhunwala, Z. Jiang, C. Watanabe, and Z. Zhang (2014) Allele specific expression detection in cancer tissues and cell lines by MBASED. Genome Biology, 15:405

31. Z. Zhang (2012), Genomic landscape of liver cancer. Nature Genetics, 44: 1075-1077

32. J. Liu, W. Lee, Z. Chen, Z. Jiang, S. Jhunjhunwala, P. M Haverty, F. Gnad, Y. Guan, H. Gilbert, J. Stinson, C. Klijn, J. Guillory, D. Bhatt, S. Vartanian, K. Walter, J. Chan, P. Dijkgraaf, S. Johnson, J. Koeman, J. Minna, A. Gazdar, H. M. Stern, K. P. Hoeflich, T. D. Wu, F. J. de Sauvage, R. C. Gentleman, R. M. Neve, D. Stokoe, Z. Modrusan, S. Seshagiri, D. S. Shames, Z. Zhang (2012) Genome and transcriptome sequencing of lung cancers reveal diverse mutational and splicing events. Genome Research, 22:2315-2327

33. S. Seshagiri, E. Stawiski, S. Durinck, Z. Modrusan, E. Storm, C. B. Conboy, S. Chaudhuri, Y. Guan, V. Janakiraman, B. S. Jaiswal, J. Guillory, C. Ha, G. J. P. Dijkgraaf, J. Stinson, F. Gnad, M. Huntley, J. D. Degenhardt, P. M. Haverty, R. Bourgon, W. Wang, H. Koeppan, R. Gentleman, T. K. Starr, Z. Zhang, D. A. Largaespada, T. D. Wu and F. J. de Sauvage (2012) Recurrent R-spondin fusions in colon cancer. Nature, 488, 660–664

34. Z. Jiang*, S. Jhunihunwala*, J. Liu, P. Haverty, K. Pant, M. I. Kennemer, P. Carnevali, Y. Guan, J. Stinson, P. Dijkgraaf, J. Rae, S. Johnson, C. Watanabe, J. Diao, S. Kapadia, F. de Sauvage, R. Gentleman, H. Stern, S. Seshagiri, Z. Modrusan, D. Ballinger, Z. Zhang (2012) The effects of hepatitis B virus integration into the genomes of hepatocellular carcinoma patients. Genome Research, 22:593-601

35. W. Lee, Z. Jiang, J. Liu, P. M. Haverty, Y. Guan, J. Stinson, P. Yue, Y. Zhang, K. P. Pant, D. Bhatt, C. Ha, S. Johnson., M. I. Kennemer, S. Mohan, I. Nazarenko, C. Watanabe, A. B. Sparks, D. S. Shames, R. Gentleman, F. J. de Sauvage, H. Stern, A. Pandita, D. G. Ballinger, R. Drmanac, Z. Modrusan, S. Seshagiri, and Z. Zhang (2010) The mutation spectrum revealed by paired genome sequences from a lung cancer patient. Nature, 465:473-477

36. Z. Kan, B. S. Jaiswal, J. Stinson, V. Janakiraman, D. Bhatt, H. M. Stern, P. Yue, P. M. Haverty, R. Bourgon, J. Zheng, M. Moorhead, S. Chaudhuri, L. P. Tomsho, B. A. Peters, K. Pujara, S. Cordes, D. P. Davis, V. E. Carlton, W. Yuan, L. Li, W. Wang, C. Eigenbrot, J. S. Kaminker, D. A. Eberhard, P. Waring, S. C. Schuster, Z. Modrusan, Z. Zhang, D. Stokoe, F. J. de Sauvage, M. Faham and S. Seshagiri. (2010) Diverse somatic mutation patterns and pathway alterations in human cancers. Nature, 466: 869-873

37. J. Liu, Y. Zhang, X. Lei, and Z. Zhang. (2008) Natural selection of protein structural and functional properties: a SNP perspective. Genome Biology, 9(4): R69

38. N. Kayagaki, Q. Phung, S. Chan, R. Chaudhari, C. Quan, K. M. O`Rourke, M. Eby, E. Pietras, G. Cheng, J. F. Bazan, Z. Zhang, D. Arnott, and V. M. Dixit. (2007) DUBA: a deubiquitinase that regulates type I interferon production. Science, 318: 1628-1632

39. L. D. Wood, D. W. Parsons, S. Jones, J. Lin, T. Sjöblom, R. J. Leary, D. Shen, S. M. Boca, T. Barber, J. Ptak, N. Silliman, S. Szabo, Z. Dezso, V. Ustyanksky, T. Nikolskaya, Y. Nikolsky, R. Karchin, P. A. Wilson, J. S. Kaminker, Z. Zhang, R. Croshaw, J. Willis, D. Dawson, M. Shipitsin, J. K. V. Willson, S. Sukumar, K. Polyak, B. H. Park, C. L. Pethiyagoda, P. V. K. Pant, D. G. Ballinger, A. B. Sparks, J. Hartigan, D. R. Smith, E. Suh, N. Papadopoulos, P. Buckhaults, S. D. Markowitz, G. Parmigiani, K. W. Kinzler, V. E. Velculescu, and B. Vogelstein. (2007) The genomic landscapes of human breast and colorectal cancers. Science, 318: 1108-1113

40. L. S. Hon and Z. Zhang. (2007) The roles of binding site arrangement and combinatorial targeting in microRNA repression of gene expression. Genome Biology, 8 (8): R166

41. J. S. Kaminker, Y. Zhang, C. Watanabe, and Z. Zhang. (2007) CanPredict: A computational tool for predicting missense cancer-associated mutations. Nucleic Acids Research, 35: W595-598

42. Y. Zhang, S-M Luoh, L. S. Hon, R. Baertsch, W. I. Wood and Z. Zhang. (2007) GeneHub-GEPIS: Digital expression profiling for normal and cancer tissues based on an integrated gene database. Nucleic Acids Research, 35: W152-158

43. J. S. Kaminker, Y. Zhang, A. Waugh, P. Haverty, J. Stinson, B. Peters, D. Sebisanovic, W. F. Forrest, J. F. Bazan, S. Seshagiri, and Z. Zhang. (2007) Distinguishing cancer associated missense mutations from common polymorphisms. Cancer Research, 67: 465-473

44. Y. Zhang, D. Eberhard, G. D. Frantz, P. Dowd, T. D. Wu, C. Watanabe, Y. Zhou, P. Polakis, K. J. Hillan, W. I. Wood, and Z. Zhang. (2004) GEPIS – Quantitative gene expression profiling in normal and cancer tissues. Bioinformatics, 20: 2390-2398

45. I. E. Wertz, K. M. O’Rourke, Z. Zhang, D. Dornan, D. Arnott, R. J. Deshaies, and V. M. Dixit. (2004) Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase. Science, 303: 1371-1374

46. Y. Zhou, S-M. Luoh, Y. Zhang, C. Watanabe, T. D. Wu, M. Ostland, W. I. Wood, and Z. Zhang. (2003) Genome-wide identification of chromosome regions of increased tumor expression by transcriptome analysis. Cancer Research, 63: 5781-5784

张泽民实验室致力于用前沿的基因组学和生物信息学技术来解决癌症生物学中的重要问题,利用计算和实验相结合方法来揭示肿瘤发生过程、肿瘤微环境和对药物响应中的系统变化和重要遗传因素,以推进癌症免疫治疗和靶向治疗的发展。主要的研究方向包括:一,应用单细胞测序技术来研究肿瘤微环境特别是肿瘤浸润免疫细胞的精确组成、相互作用、以及功能状态;二,研究肿瘤的异质性、基因组机制、及其对耐药性的影响;三,开发原创的生物信息学工具和数据库,来进行单细胞基因组数据和癌症基因组大数据的整合、分析和可视化,以揭示癌症的亚型、驱动基因以及其他致癌因素的遗传基础,从而发现新型癌症靶点和标记物。


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