Photo of Cheng-Zhong Zhang,  PhD

Cheng-Zhong Zhang, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 582-9886
Fax: (617) 582-7260


cheng-zhong_zhang@dfci.harvard.edu

Cheng-Zhong Zhang, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Assistant Professor, Biomedical Informatics, Harvard Medical School
  • Assistant Professor, Biostatistics & Computational Biology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

My laboratory studies chromosomal abnormalities in cancer. Examples of such alterations include aneuploidy, whole-genome duplication, and complex chromosomal rearrangements. Despite their prevalence, the origin and functional impact of these alterations in cancer evolution remains an unsolved problem. My research addresses this question from three different angles using DNA sequencing as a high-throughput, high-resolution assay.

The first focus of my research is to characterize chromosomal abnormalities at high resolution. The ultimate goal of this project is to assemble the end-to-end sequence of aberrant chromosomes (10-100 Mb) in cancer genomes and use this information to infer the history of cancer genome evolution. After determining the sequence of rearranged chromosomes, the next focus of my laboratory is to identify the molecular/cellular mechanisms that generate these alterations combining single-cell DNA sequencing with cell biology experiments. Finally, we use single-cell transcriptome analysis to study transcriptional variation due to chromosomal abnormalities with a focus on understanding the tissue-specific functional impact of these alterations.

Publications

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  • Lohr JG, Kim S, Gould J, Knoechel B, Drier Y, Cotton MJ, Gray D, Birrer N, Wong B, Ha G, Zhang CZ, Guo G, Meyerson M, Yee AJ, Boehm JS, Raje N, Golub TR. Genetic interrogation of circulating multiple myeloma cells at single-cell resolution. Sci Transl Med 2016; 8:363ra147. PubMed
  • Wala J, Zhang CZ, Meyerson M, Beroukhim R. VariantBam: filtering and profiling of next-generational sequencing data using region-specific rules. Bioinformatics 2016; 32:2029-31. PubMed
  • Aguirre AJ, Meyers RM, Weir BA, Vazquez F, Zhang CZ, Ben-David U, Cook A, Ha G, Harrington WF, Doshi MB, Kost-Alimova M, Gill S, Xu H, Ali LD, Jiang G, Pantel S, Lee Y, Goodale A, Cherniack AD, Oh C, Kryukov G, Cowley GS, Garraway LA, Stegmaier K, Roberts CW, Golub TR, Meyerson M, Root DE, Tsherniak A, Hahn WC. Genomic copy number dictates a gene-independent cell response to CRISPR-Cas9 targeting. 2016. PubMed
  • Zhang CZ, Pellman D. From Mutational Mechanisms in Single Cells to Mutational Patterns in Cancer Genomes. Cold Spring Harb Symp Quant Biol 2016. PubMed
  • Leibowitz ML, Zhang CZ, Pellman D. Chromothripsis: A New Mechanism for Rapid Karyotype Evolution. Annu Rev Genet 2015; 49:183-211. PubMed
  • Elvers I, Turner-Maier J, Swofford R, Koltookian M, Johnson J, Stewart C, Zhang CZ, Schumacher SE, Beroukhim R, Rosenberg M, Thomas R, Mauceli E, Getz G, Palma FD, Modiano JF, Breen M, Lindblad-Toh K, Alföldi J. Exome sequencing of lymphomas from three dog breeds reveals somatic mutation patterns reflecting genetic background. Genome Res 2015. PubMed
  • Zhang CZ, Spektor A, Cornils H, Francis JM, Jackson EK, Liu S, Meyerson M, Pellman D. Chromothripsis from DNA damage in micronuclei. Nature 2015; 522:179-84. PubMed
  • Zhang CZ, Adalsteinsson VA, Francis J, Cornils H, Jung J, Maire C, Ligon KL, Meyerson M, Love JC. Calibrating genomic and allelic coverage bias in single-cell sequencing. Nat Commun 2015; 6:6822. PubMed
  • Yang L, Grishin D, Wang G, Aach J, Zhang CZ, Chari R, Homsy J, Cai X, Zhao Y, Fan JB, Seidman C, Seidman J, Pu W, Church G. Targeted and genome-wide sequencing reveal single nucleotide variations impacting specificity of Cas9 in human stem cells. Nat Commun 2014; 5:5507. PubMed
  • Francis JM, Zhang CZ, Maire CL, Jung J, Manzo VE, Adalsteinsson VA, Homer H, Haidar S, Blumenstiel B, Pedamallu CS, Ligon AH, Love JC, Meyerson M, Ligon KL. EGFR variant heterogeneity in glioblastoma resolved through single-nucleus sequencing. 2014. PubMed
  • Lohr JG, Adalsteinsson VA, Cibulskis K, Choudhury AD, Rosenberg M, Cruz-Gordillo P, Francis JM, Zhang CZ, Shalek AK, Satija R, Trombetta JJ, Lu D, Tallapragada N, Tahirova N, Kim S, Blumenstiel B, Sougnez C, Lowe A, Wong B, Auclair D, Van Allen EM, Nakabayashi M, Lis RT, Lee GS, Li T, Chabot MS, Ly A, Taplin ME, Clancy TE, Loda M, Regev A, Meyerson M, Hahn WC, Kantoff PW, Golub TR, Getz G, Boehm JS, Love JC. Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. Nat Biotechnol 2014. PubMed
  • Zhang CZ, Leibowitz ML, Pellman D. Chromothripsis and beyond: rapid genome evolution from complex chromosomal rearrangements. Genes Dev 2013; 27:2513-30. PubMed
  • Kim J, Zhang CZ, Zhang X, Springer TA. A mechanically stabilized receptor-ligand flex-bond important in the vasculature. Nature 2010; 466:992-5. PubMed
  • Zhang X, Halvorsen K, Zhang CZ, Wong WP, Springer TA. Mechanoenzymatic cleavage of the ultralarge vascular protein von Willebrand factor. Science 2009; 324:1330-4. PubMed
  • Zhang Q,Zhou YF,Zhang CZ,Zhang X,Lu C,Springer TA. Structural specializations of A2, a force-sensing domain in the ultralarge vascular protein von Willebrand factor. Proc Natl Acad Sci U S A 2009. PubMed
  • Zhang CZ, Wang ZG. Nucleation of membrane adhesions. Phys Rev E Stat Nonlin Soft Matter Phys 2008; 77:021906. PubMed
  • Zhang CZ, Wang ZG. Polymer-tethered ligand-receptor interactions between surfaces II. Langmuir 2007; 23:13024-39. PubMed
  • Zhang CZ, Wang ZG. Random isotropic structures and possible glass transitions in diblock copolymer melts. Phys Rev E Stat Nonlin Soft Matter Phys 2006; 73:031804. PubMed
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