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, PhD

Dana-Farber Cancer Institute


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


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 from Harvard Catalyst Profiles

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  • Papathanasiou S, Mynhier NA, Liu S, Brunette G, Stokasimov E, Jacob E, Li L, Comenho C, van Steensel B, Buenrostro JD, Zhang CZ, Pellman D. Heritable transcriptional defects from aberrations of nuclear architecture. Nature 2023; 619:184-192. PubMed
  • Sinha S, Zhang CZ. Determining Complete Chromosomal Haplotypes by mLinker. Methods Mol Biol 2023; 2590:149-159. PubMed
  • Sadagopan A, Nasim IT, Li J, Achom M, Zhang CZ, Viswanathan SR. Somatic XIST activation and features of X chromosome inactivation in male human cancers. Cell Syst 2022; 13:932-944.e5. PubMed
  • Waldschmidt JM, Yee AJ, Vijaykumar T, Pinto RA, Frede J, Anand P, Bianchi G, Guo G, Potdar S, Seifer C, Nair MS, Kokkalis A, Kloeber JA, Shapiro S, Budano L, Mann M, Friedman R, Lipe B, Campagnaro E, O'Donnell EK, Zhang CZ, Laubach JP, Munshi NC, Richardson PG, Anderson KC, Raje NS, Knoechel B, Lohr JG. Cell-free DNA for the detection of emerging treatment failure in relapsed/ refractory multiple myeloma. Leukemia 2022; 36:1078-1087. PubMed
  • Tourdot RW, Brunette GJ, Pinto RA, Zhang CZ. Determination of complete chromosomal haplotypes by bulk DNA sequencing. Genome Biol 2021; 22:139. PubMed
  • Leibowitz ML, Papathanasiou S, Doerfler PA, Blaine LJ, Sun L, Yao Y, Zhang CZ, Weiss MJ, Pellman D. Chromothripsis as an on-target consequence of CRISPR-Cas9 genome editing. Nat Genet 2021. PubMed
  • Papathanasiou S, Markoulaki S, Blaine LJ, Leibowitz ML, Zhang CZ, Jaenisch R, Pellman D. Whole chromosome loss and genomic instability in mouse embryos after CRISPR-Cas9 genome editing. Nat Commun 2021; 12:5855. PubMed
  • Cortés-Ciriano I, Lee JJ, Xi R, Jain D, Jung YL, Yang L, Gordenin D, Klimczak LJ, Zhang CZ, Pellman DS, , Park PJ, . Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing. Nat Genet 2020; 52:331-341. PubMed
  • Umbreit NT, Zhang CZ, Lynch LD, Blaine LJ, Cheng AM, Tourdot R, Sun L, Almubarak HF, Judge K, Mitchell TJ, Spektor A, Pellman D. Mechanisms generating cancer genome complexity from a single cell division error. Science 2020. PubMed
  • Song W, Huang H, Zhang CZ, Bates DW, Wright A. Using whole genome scores to compare three clinical phenotyping methods in complex diseases. Sci Rep 2018; 8:11360. PubMed
  • Viswanathan SR, Ha G, Hoff AM, Wala JA, Carrot-Zhang J, Whelan CW, Haradhvala NJ, Freeman SS, Reed SC, Rhoades J, Polak P, Cipicchio M, Wankowicz SA, Wong A, Kamath T, Zhang Z, Gydush GJ, Rotem D, , Love JC, Getz G, Gabriel S, Zhang CZ, Dehm SM, Nelson PS, Van Allen EM, Choudhury AD, Adalsteinsson VA, Beroukhim R, Taplin ME, Meyerson M. Structural Alterations Driving Castration-Resistant Prostate Cancer Revealed by Linked-Read Genome Sequencing. Cell 2018. PubMed
  • Adalsteinsson VA, Ha G, Freeman SS, Choudhury AD, Stover DG, Parsons HA, Gydush G, Reed SC, Rotem D, Rhoades J, Loginov D, Livitz D, Rosebrock D, Leshchiner I, Kim J, Stewart C, Rosenberg M, Francis JM, Zhang CZ, Cohen O, Oh C, Ding H, Polak P, Lloyd M, Mahmud S, Helvie K, Merrill MS, Santiago RA, O'Connor EP, Jeong SH, Leeson R, Barry RM, Kramkowski JF, Zhang Z, Polacek L, Lohr JG, Schleicher M, Lipscomb E, Saltzman A, Oliver NM, Marini L, Waks AG, Harshman LC, Tolaney SM, Van Allen EM, Winer EP, Lin NU, Nakabayashi M, Taplin ME, Johannessen CM, Garraway LA, Golub TR, Boehm JS, Wagle N, Getz G, Love JC, Meyerson M. Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors. Nat Commun 2017; 8:1324. PubMed
  • 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