张泽民 邮  箱：zeminz@yahoo.com
职  称：教授
办公室地址：北京市海淀区颐和园路5号，北京大学，综合科研楼，100871
实验室地址：北京市海淀区颐和园路5号，北京大学，综合科研楼，100871
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:张博士于南开大学获得遗传学学士学位，于美国宾州州立大学获得生物化学与分子生物学博士学位。此外他还在加州大学伯克利分校获得了IT技术的训练，在加州大学旧金山分校的医学实验室完成了博士后训练。在加入北京大学之前，张博士在著名生物医药公司基因泰克/罗氏（Genentech/Roche）工作了16年，担任癌症基因组学和生物信息学组的首席，致力于应用机器学习和高通量测序等高新技术进行抗癌药靶和生物标记物的发现。他在计算癌症生物学和癌症基因组学的多个方向上都是开拓者、引领者，如世界首例肿瘤全基因组测序即由张博士领导完成。张博士同时也是60个已获得授权的美国专利的发明人，并在目前正在临床试验中的多项癌症治疗药物的分子靶标的原创发现中做出了直接贡献。他同时也是多家国际知名杂志如Cell Systems、Genome Medicine和Cancer Informatics的编委。
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, Z. Zhang (2017). Landscape of Infiltrating T Cells in Liver Cancer Revealed by Single-Cell Sequencing. Cell, 169(7), 1342–1356.e16.
Tang, Z., Li, C., Kang, B., Gao, G., Li, C., & Zhang, Z. (2017). GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic acids research.
Z. Tang, C. Li, K. Zhang, M. Yang, and X. Hu. (2017) GE-mini: a mobile APP for large-scale gene expression visualization. Bioinformatics.
X. Hu and Z. Zhang. (2016) Understanding the Genetic Mechanisms of Cancer Drug Resistance Using Genomic Approaches. Trends In Genetics. 32(2):127-37.
R. Xue, R. Li, H. Guo, L. Guo, Z. Su, X. Ni, L. Qi, T. Zhang, Q. Li, Z. Zhang, X.S. Xie, F. Bai, and N. Zhang. (2016) Variable Extent of Intra-tumor Heterogeneity Revealed by Genomic Sequencing of Multiple Lesions in Patients with Hepatocellular Carcinoma. Gastroenterology. pii: S0016-5085(15)01861-2
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 (* co-corresponding authors)
Z. Wang, Z. Shen, Z. Li, J. Duan, S. Fu, Z. Liu, H. Bai, Z. Zhang, J. Zhao, X. Wang, J. Wang (2015) Activation of the BMP-BMPR pathway conferred resistance to EGFR-TKIs in lung squamous cell carcinoma patients with EGFR mutations. Proc Natl Acad Sci U S A. 112:9990-5
F. Gnad*, S. Doll, G. Manning, D. Arnott, Z. Zhang* (2015) Bioinformatics analysis of thousands of TCGA tumors to determine the involvement of epigenetic regulators in human cancer. BMC Genomics. 16:S5
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
L. 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 Communication, 5:3830, doi: 10.1038/ncomms4830
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
G. Lee, P. M. Haverty, L. Li, N. Kljavin, R. Bourgon, J. Lee, H. M. Stern, Z. Modrusan, S. Seshagiri, Z. Zhang, D. Davis, D. Stokoe, J. Settleman, F. J. de Sauvage, and R. M. Neve. (2014) Comparative oncogenomics identifies PSMB4 and SHMT2 as potential cancer driver genes. Cancer Research, 74:3114-26
A. Adler, V. Chopra, M.L. McCleland, S. Hussain, G. Quinones, Z. Modrusan, S. Seshagiri, E. Torres, B. Haley, Z. Zhang, E.M. Blackwood, M. Singh, M. Junttila, J. Stephan, E. Fearson, Z. Jiang, and R. Firestein. (2014) An integrative analysis of colon cancer identifies an essential function for PRPF6 in tumor growth. Genes and Development, 28:1068-84
O. Mayba, F. Gnad, F. Zhang, K. Walter, P. Du, M. A. Huntley, Z. Jiang, J. Liu, P. M. Haverty, R. Li, M. Peyton, J. D. Minna, Y. Li, D. S. Shames, and Z. Zhang. (2014) Integrative analysis of two cell lines derived from a non-small-lung cancer patient – a panomics approach. Pac Symp Biocomput. 2014:75-86
W. Yuan, E. Stawiski, V. Janakiraman, E. Chan, S. Durinck, K. Edgar, N. M. Kljavin, C. S. Rivers, F. Gnad, M. Roose-Girma, P. M. Haverty, G. Fedorowicz, S. Heldens, R.H. Soriano, Z. Zhang, J. Wallin, L. Johnson, M. Merchant, Z. Modrusan, H. Stern, and S. Seshagiri. (2013) Conditional activation of PIK3CA (H1047R) in a knock-in mouse promotes mammary tumorigenesis and emergence of mutations. Oncogene, 32:318-326
F. Gnad, A. Baucom, K. Mukhyala, G. Manning, and Zhang Z. (2013) Assessment of computational methods for predicting the effects of missense mutations in human cancers. BMC Genomics, 14:S7
F. Hwang, G. Atluri, R. Kuang, V. Humar, T. Starr, K.AT.Siverstein, P.M. Haverty, Z. Zhang, and J. Liu. (2013), Large-scale integrative network-based analysis identifies common pathways disrupted by copy number alterations across cancers”. BMC Genomics, 14:440
Z. Zhang. (2012), Genomic landscape of liver cancer. Nature Genetics, 44: 1075-1077
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, and Z. Zhang. (2012) Genome and transcriptome sequencing of lung cancers reveal diverse mutational and splicing events. Genome Research, 22:2315-2327
C. M. Rudin, S. Durinck, E. W. Stawiski, J. T. Poirier, Z. Modrusan, D. Shames, E. A. Bergbower, Y. Guan, J. Shin, J. Guillory, C. S. Rivers, C. Foo, D. Bhatt, J. Stinson, F. Gnad, P. M. Haverty, R. Gentleman, S. Chaudhuri, V. Janakiraman, B. S. Jaiswal, C. Parikh, W. Yuan, Z. Zhang, H. Koeppen, T. D. Wu, H. M Stern, R. L. Yauch, K. E. Huffman, D. D. Paskulin, P. B. Illei, M. Varella-Garcia, A. F. Gazdar, F. J. de Sauvage, R. Bourgon, J. D. Minna, M. V. Brock, and S. Seshagiri. (2012) Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small cell lung cancer. Nature Genetics, 44: 1111-1116
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
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, and Z. Zhang. (2012) The effects of hepatitis B virus integration into the genomes of hepatocellular carcinoma patients. Genome Research, 22:593-601 (cover article)
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
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
P. Yue, J. S. Kaminker, W. F. Forrest, S. Lohr, Z. Zhang and G. Cavet. (2010) Inferring the functional effects of mutation through clusters of mutations in homologous proteins. Human Mutation, 31 (3): 264-271
W. Lee, Y. Zhang, K. Mukhyala, R. Lazarus and Z. Zhang. (2009) Bi-directional SIFT predicts a subset of activating mutations. PLoS ONE, 4 (12): e8311. doi:10.1371/journal.pone.**
W. Lee, P. Yue, and Z. Zhang. (2009) Analytical methods for inferring functional effects of single base-pair substitutions in human cancers. Human Genetics, 126:481-498
L. S. Hon, Y. Zhang, J. S. Kaminker, and Z. Zhang. (2009) Computational prediction of the functional effects of amino acid substitutions in signal peptides using a model-based approach. Human Mutation, 30 (1): 99-106
P. M. Haverty, L. S. Hon, J. S. Kaminker, J. Chant*, and Z. Zhang*. (2009) High-resolution analysis of copy number alterations and associated expression changes in ovarian tumors. BMC Medical Genomics, 2:21 (* co-corresponding authors)
H. Jin, R. Yang, Z. Zheng, M. Romero, J. Ross, H. Bou-Reslan, R. A. D. Carano, I. Kasman, E. Mai, J. Young, J. Zha, Z. Zhang, S. Ross, R. Schwall, G. Colbern, and M. Merchant. (2008) MetMAb, the one-armed 5D5 anti-c-Met antibody, inhibits orthotopic pancreatic tumor growth and improves survival. Cancer Research, 68 (11): 4360-4368
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
P. M. Haverty, J. Fridlyand, L. Li, G. Getz, R. Beroukhim, S. Lohr, T. D. Wu, G. Cavet, Z. Zhang*, and J. Chant*. (2008) High-resolution genomic and expression analyses of copy number alterations in breast tumors. Genes, Chromosomes and Cancer, 47: 530-542 (* co-corresponding authors)
H. S. Hon, J. S. Kaminker, and Z. Zhang. (2008) Computational approaches for predicting causal missense mutations in cancer genome projects. Current Bioinformatics, 3 (1): 46-55
L. D. Wood, D. W. Parsons, S. Jones, J. Lin, T. Sj?blom, 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
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
H. 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
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
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
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
D. Gray, A. M. Jubb, D. Hogue, P. Dowd, N. Kljavin, S. Yi, G. Frantz, W. Bai, Z. Zhang, H. Koeppen, F. de Sauvage, and D. Davis. (2005) Maternal Embryonic Leucine Zipper Kinase/Murine Protein Serine-Threonine Kinase 38 is a promising therapeutic target for multiple cancers. Cancer Research, 65: 97511-9761
Z. Zhang* and W. J. Henzel. (2004) Signal peptide prediction based on analysis of experimentally verified cleavage sites. Protein Science, 13: 2819-2824 (* first and corresponding author)
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
B. Desany and Z. Zhang. (2004) Bioinformatics and cancer target discovery. Drug Discov. Today, 9: 795-802
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
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
K. M. L. Gaensler, Z. Zhang, C. Lin, S. Yang, K. Hardt, and L. Flebbe-Rehwaldt. (2003) Sequences in the Ag – d intergenic regions are not required for stage-specific regulation of the human b-globin gene locus. Proc. Natl. Acad. Sci. USA, 100 (6): 3374-3379
Z. Zhang* and W. I. Wood. (2003) A profile hidden Markov model for signal peptides generated by HMMER. Bioinformatics, 19 (2): 307-308 (* first and corresponding author)
我们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，结合计算（干）和实验（湿）方法来揭示肿瘤发生过程、微环境和对药物响应中的系统变化和具体遗传因素，以推进癌症免疫治疗和靶向治疗的发展。首先，我们应用单细胞测序技术来研究肿瘤微环境，特别是浸润肿瘤免疫细胞的精确组成和功能状态，应用单细胞测序技术来研究肿瘤的异质性以及各种异质性对癌细胞的功能和药敏的影响。第二，我们将尖端生物信息学方法应用到癌症基因组学大数据中，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，如基因融合、等位基因差异表达、肿瘤特有的转录异构体等，从而发现新型癌症靶点和标记物。第三，我们开发原创性的生物信息学工具来进行单细胞基因组数据和大规模癌症基因组学数据的分析、整合和可视化，为对这些数据的有效挖掘提供基础。