Zemin Zhang
Principal Scientist: Bioinformatics & Computational Biology
"Cancer genomes hold secrets to how tumors arise, develop, and respond to drugs. In the near future computational modeling and analysis of these cancer genomes will become a dominant force in cancer biology and therapeutics. It is inspiring to be in the middle of such an opportunity of a lifetime."
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My Keywords
Bioinformatics, Computational Biology, Oncology, Protein Chemistry -
My Department
Bioinformatics & Computational Biology
I came to Genentech in January 1998 to join a large research program that used genomics technologies to find novel secreted proteins with therapeutic potential.
Subsequently I have participated in a series of target discovery initiatives in which bioinformatics has played a pivotal role in identifying kinases or cell surface proteins with desirable physicochemical and expression characteristics. It is gratifying to see that computational approaches are directly contributing to our early-stage drug pipeline. At the same time, my collaborations with experimental scientists have inspired new research directions in bioinformatics that are relevant and interesting. The ability to do both basic and applied research has been a major attraction to many scientists, including myself.
My Focus
Recently my group has undertaken very broad cancer genome characterization studies, which require close collaboration with scientists from the sequencing facility, the microarray lab, the pathology and tissue groups, the diagnostics team, and other programmers and computational biologists.
Cancer genomics has been our long-lasting interests. Next generation sequencing technologies provide unprecedented opportunities to reveal mysteries hidden in the complex mutational landscape of cancer. One aspect of our current work is to use emerging technologies such as the Complete Genomics platform to perform whole genome sequencing of cancer samples. Using the short-read sequence data, we are in the process of characterizing a wide variety of genetic alterations including point mutations and structural variations. In combination with other data types such as expression microarrays, SNP arrays, and Illumina-based RNA-Seq, we are studying how new insights from whole genome information can help us understand cancer biology and drug response.
Another complementary aspect of our current work is the use of computational methods to predict the functional consequence of a given genetic lesion. This has been an active research area in my group, and I expect we will continue to leverage our expertise in this domain to distinguish driver from passenger mutations in cancer genomes.
Publications & Recognition
- The mutation spectrum revealed by paired genome sequences from a lung cancer patient
- Nature 2010
- Lee W, Jiang Z, Liu J, Haverty PM, Guan Y, Stinson J, Yue P, Zhang Y, Pant KP, Bhatt D, Ha C, Johnson S, Kennemer MI, Mohan S, Nazarenko I, Watanabe C, Sparks AB, Shames DS, Gentleman R, de Sauvage FJ, Stern H, Pandita A, Ballinger DG, Drmanac R, Modrusan Z, Seshagiri S, Zhang Z
- Inferring the functional effects of mutation through clusters of mutations in homologous proteins
- Hum Mutat 2010 Mar; 31(3): 264-71
- Yue P, Forrest WF, Kaminker JS, Lohr S, Zhang Z, Cavet G
- View Abstract on PubMed
- Bi-directional SIFT predicts a subset of activating mutations
- PLoS One.; 4(12): e8311
- Lee W, Zhang Y, Mukhyala K, Lazarus RA, Zhang Z
- View Abstract on PubMed
- University of California, San Francisco
- Postdoctoral Fellow
- 1995-1998
- Pennsylvania State University, Biochemistry and Molecular Biology
- Ph.D.
- 1989-1995
- China-United States Biochemistry and Molecular Biology Training Program
- 1988-1989
- Nankai University, Genetics
- B.S.
- 1984-1988
Publications & Recognition
- The mutation spectrum revealed by paired genome sequences from a lung cancer patient
- Nature 2010
- Lee W, Jiang Z, Liu J, Haverty PM, Guan Y, Stinson J, Yue P, Zhang Y, Pant KP, Bhatt D, Ha C, Johnson S, Kennemer MI, Mohan S, Nazarenko I, Watanabe C, Sparks AB, Shames DS, Gentleman R, de Sauvage FJ, Stern H, Pandita A, Ballinger DG, Drmanac R, Modrusan Z, Seshagiri S, Zhang Z
- Inferring the functional effects of mutation through clusters of mutations in homologous proteins
- Hum Mutat 2010 Mar; 31(3): 264-71
- Yue P, Forrest WF, Kaminker JS, Lohr S, Zhang Z, Cavet G
- View Abstract on PubMed
- Bi-directional SIFT predicts a subset of activating mutations
- PLoS One.; 4(12): e8311
- Lee W, Zhang Y, Mukhyala K, Lazarus RA, Zhang Z
- View Abstract on PubMed
- Analytical methods for inferring functional effects of single base pair substitutions in human cancers
- Hum Genet. 2009 Oct; 126(4): 481-98
- Lee W, Yue P, Zhang Z
- View Abstract on PubMed
- Computational prediction of the functional effects of amino acid substitutions in signal peptides using a model-based approach
- Hum Mutat 2009 Jan; 30(1): 99-106
- Hon LS, Zhang Y, Kaminker JS, Zhang Z
- View Abstract on PubMed
- High-resolution analysis of copy number alterations and associated expression changes in ovarian tumors
- BMC Med Genomics 2009 May 6; 2:21
- Haverty PM, Hon LS, Kaminker JS, Chant J, Zhang Z
- View Abstract on PubMed
- MetMAb, the one-armed 5D5 anti-c-Met antibody, inhibits orthotopic pancreatic tumor growth and improves survival
- Cancer Res. 2008 Jun 1; 68(11): 4360-8
- Jin H, Yang R, Zheng Z, Romero M, Ross J, Bou-Reslan H, Carano RA, Kasman I, Mai E, Young J, Zha J, Zhang Z, Ross S, Schwall R, Colbern G, Merchant M
- View Abstract on PubMed
- Natural selection of protein structural and functional properties: a single nucleotide polymorphism perspective
- Genome Biol 2008 Apr 8; 9(4): R69
- Liu J, Zhang Y, Lei X, Zhang Z
- View Abstract on PubMed
- High-resolution genomic and expression analyses of copy number alterations in breast tumors
- Genes Chromosomes Cancer 2008 Jun; 47(6): 530-42
- Haverty PM, Fridlyand J, Li L, Getz G, Beroukhim R, Lohr S, Wu TD, Cavet G, Zhang Z, Chant J
- View Abstract on PubMed
- Computational approaches for predicting causal missense mutations in cancer genome projects
- Current Bioinformatics. 2008; 3(1): 46-55
- Hon LS, Kaminker JS, Zhang Z
- DUBA: a deubiquitinase that regulates type I interferon production
- Science 2007 Dec 7; 318(5856): 1628-32
- Kayagaki N, Phung Q, Chan S, Chaudhari R, Quan C, O'Rourke KM, Eby M, Pietras E, Cheng G, Bazan JF, Zhang Z, Arnott D, Dixit VM
- View Abstract on PubMed
- The genomic landscapes of human breast and colorectal cancers
- Science 2007 Nov 16; 318(5853): 1108-13
- Wood LD, Parsons DW, Jones S, Lin J, Sjoblom T, Leary RJ, Shen D, Boca SM, Barber T, Ptak J, Silliman N, Szabo S, Dezso Z, Ustyanksky V, Nikolskaya T, Nikolsky Y, Karchin R, Wilson PA, Kaminker JS, Zhang Z, Croshaw R, Willis J, Dawson D, Shipitsin M, Willson JK, Sukumar S, Polyak K, Park BH, Pethiyagoda CL, Pant PV, Ballinger DG, Sparks AB, Hartigan J, Smith DR, Suh E, Papadopoulos N, Buckhaults P, Markowitz SD, Parmigiani G, Kinzler KW, Velculescu VE, Vogelstein B
- View Abstract on PubMed
- The roles of binding site arrangement and combinatorial targeting in microRNA repression of gene expression
- Genome Biol 2007; 8(8): R166
- Hon LS, Zhang Z
- View Abstract on PubMed
- CanPredict: a computational tool for predicting cancer-associated missense mutations
- Nucleic Acids Res 2007 Jul; 35(Web Server issue): W595-8
- Kaminker JS, Zhang Y, Watanabe C, Zhang ZF
- View Abstract on PubMed
- GeneHub-GEPIS: digital expression profiling for normal and cancer tissues based on an integrated gene database
- Nucleic Acids Res 2007 Jul; 35(Web Server issue): W152-8
- Zhang Y, Luoh SM, Hon LS, Baertsch R, Wood WI, Zhang Z
- View Abstract on PubMed
- Distinguishing cancer-associated missense mutations from common polymorphisms
- Cancer Res 2007 Jan 15; 67(2): 465-73
- Kaminker JS, Zhang Y, Waugh A, Haverty PM, Peters B, Sebisanovic D, Stinson J, Forrest WF, Bazan JF, Seshagiri S, Zhang Z
- View Abstract on PubMed
- Expression profiling of the mouse prostate after castration and hormone replacement: implication of H-cadherin in prostate tumorigenesis
- Differentiation 2007 Mar; 75(3): 219-34
- Wang XD, Wang BE, Soriano R, Zha J, Zhang Z, Modrusan Z, Cunha GR, Gao WQ
- View Abstract on PubMed
- Maternal embryonic leucine zipper kinase/murine protein serine-threonine kinase 38 is a promising therapeutic target for multiple cancers
- Cancer Res. 2005 Nov 1; 65(21): 9751-61
- Gray D, Jubb AM, Hogue D, Dowd P, Kljavin N, Yi S, Bai W, Frantz G, Zhang Z, Koeppen H, de Sauvage FJ, Davis DP
- View Abstract on PubMed
- Signal peptide prediction based on analysis of experimentally verified cleavage sites
- Protein Sci 2004 Oct; 13(10): 2819-24
- Zhang Z, Henzel WJ
- View Abstract on PubMed
- GEPIS--quantitative gene expression profiling in normal and cancer tissues
- Bioinformatics 2004 Oct 12; 20(15): 2390-8
- Zhang Y, Eberhard DA, Frantz GD, Dowd P, Wu TD, Zhou Y, Watanabe C, Luoh SM, Polakis P, Hillan KJ, Wood WI, Zhang Z
- View Abstract on PubMed
- Bioinformatics and cancer target discovery
- Drug Discov Today 2004 Sep 15; 9(18): 795-802
- Desany B, Zhang Z
- View Abstract on PubMed
- Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase
- Science 2004 Feb 27; 303(5662): 1371-4
- Wertz IE, O'Rourke KM, Zhang Z, Dornan D, Arnott D, Deshaies RJ, Dixit VM
- View Abstract on PubMed
- Genome-wide identification of chromosomal regions of increased tumor expression by transcriptome analysis
- Cancer Res 2003 Sep 15; 63(18): 5781-4
- Zhou Y, Luoh SM, Zhang Y, Watanabe C, Wu TD, Ostland M, Wood WI, Zhang Z
- View Abstract on PubMed
- Sequences in the (A)gamma-delta intergenic region are not required for stage-specific regulation of the human beta-globin gene locus
- Proc Natl Acad Sci USA 2003 Mar 18; 100(6): 3374-9
- Gaensler KM, Zhang Z, Lin C, Yang S, Hardt K, Flebbe-Rehwaldt L
- View Abstract on PubMed
- A profile hidden Markov model for signal peptides generated by HMMER
- Bioinformatics 2003 Jan 22; 19(2): 307-8
- Zhang Z, Wood WI
- View Abstract on PubMed
- Mouse endocrine gland-derived vascular endothelial growth factor: a distinct expression pattern from its human ortholog suggests different roles as a regulator of organ-specific angiogenesis
- Endocrinology. 2003 Jun; 144(6): 2606-16
- LeCouter J, Lin R, Frantz G, Zhang Z, Hillan K, Ferrara N
- View Abstract on PubMed
- The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment
- Genome Res 2003 Oct; 13(10): 2265-70
- Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A
- View Abstract on PubMed
- Identification of a novel death domain-containing adaptor molecule for ectodysplasin-A receptor that is mutated in crinkled mice
- Curr Biol 2002 Mar 5; 12(5): 409-13
- Yan M, Zhang Z, Brady JR, Schilbach S, Fairbrother WJ, Dixit VM
- View Abstract on PubMed
- Identification of an angiogenic mitogen selective for endocrine gland endothelium
- Nature. 2001 Aug 30; 412(6850): 877-84
- LeCouter J, Kowalski J, Foster J, Hass P, Zhang Z, Dillard-Telm L, Frantz G, Rangell L, DeGuzman L, Keller GA, Peale F, Gurney A, Hillan KJ, Ferrara N
- View Abstract on PubMed
- Cleavage and identification of proteins: a modified aspartyl-prolyl cleavage
- Anal Chem 2000 Nov 1; 72(21): 5431-6
- Kishiyama A, Zhang Z, Henzel WJ
- View Abstract on PubMed
- Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R
- J Biol Chem 2000 Oct 6; 275(40): 31335-9
- Xie MH, Aggarwal S, Ho WH, Foster J, Zhang Z, Stinson J, Wood WI, Goddard AD, Gurney AL
- View Abstract on PubMed
- The human beta globin locus introduced by YAC transfer exhibits a specific and reproducible pattern of developmental regulation in transgenic mice
- Blood 1997 Dec 1; 90(11): 4602-9
- Porcu S, Kitamura M, Witkowska E, Zhang Z, Mutero A, Lin C, Chang J, Gaensler KM
- View Abstract on PubMed
- Identification of a member of a DNA-dependent ATPase family that causes interference with silencing
- Mol Cell Biol 1997 Sep; 17(9): 5461-72
- Zhang Z, Buchman AR
- View Abstract on PubMed
Awards & Honors
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Sigma Xi Research Grant--1995
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CUSBEA Scholar--1989
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Tianjin Intercollegiate Scholarship--1988
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Nankai College Scholarship--1987
