Photo of Lee Zou,  PhD

Lee Zou, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 724-9534


zou.lee@mgh.harvard.edu

Lee Zou, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Professor, Pathology, Harvard Medical School
  • Associate Scientific Director, MGH Cancer Center, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

My research focuses on understanding how cells detect and signal DNA damage and maintain genomic stability. In response to DNA damage or DNA replication problems, cells activate a signaling pathway called the checkpoint to regulate and coordinate various cellular processes to keep the genome stable. The ATR protein kinase is a central player for checkpoint signaling. We are currently investigating how cells recognize different types of DNA damage and activate ATR. We are also studying how activated ATR signals DNA damage in cells and regulates downstream processes such as DNA replication and repair. Given the solid link between loss of genomic stability and cancer development, our study may shed new light on the role of checkpoint as an anti-cancer barrier.

Publications

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  • Flynn RL, Cox KE, Jeitany M, Wakimoto H, Bryll AR, Ganem NJ, Bersani F, Pineda JR, Suvà ML, Benes CH, Haber DA, Boussin FD, Zou L. Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors. Science 2015; 347:273-7. PubMed
  • Ouyang J, Garner E, Hallet A, Nguyen HD, Rickman KA, Gill G, Smogorzewska A, Zou L. Noncovalent interactions with SUMO and ubiquitin orchestrate distinct functions of the SLX4 complex in genome maintenance. Mol Cell 2015; 57:108-22. PubMed
  • Maréchal A, Zou L. RPA-coated single-stranded DNA as a platform for post-translational modifications in the DNA damage response. Cell Res 2015; 25:9-23. PubMed
  • Manning AL, Yazinski SA, Nicolay B, Bryll A, Zou L, Dyson NJ. Suppression of genome instability in pRB-deficient cells by enhancement of chromosome cohesion. Mol Cell 2014; 53:993-1004. PubMed
  • Maréchal A, Li JM, Ji XY, Wu CS, Yazinski SA, Nguyen HD, Liu S, Jiménez AE, Jin J, Zou L. PRP19 transforms into a sensor of RPA-ssDNA after DNA damage and drives ATR activation via a ubiquitin-mediated circuitry. Mol Cell 2014; 53:235-46. PubMed
  • Ogiwara H, Ui A, Shiotani B, Zou L, Yasui A, Kohno T. Curcumin suppresses multiple DNA damage response pathways and has potency as a sensitizer to PARP inhibitor. Carcinogenesis 2013; 34:2486-97. PubMed
  • Pfäffle HN, Wang M, Gheorghiu L, Ferraiolo N, Greninger P, Borgmann K, Settleman J, Benes CH, Sequist LV, Zou L, Willers H. EGFR-activating mutations correlate with a Fanconi anemia-like cellular phenotype that includes PARP inhibitor sensitivity. Cancer Res 2013; 73:6254-63. PubMed
  • Shiotani B, Nguyen HD, Håkansson P, Maréchal A, Tse A, Tahara H, Zou L. Two distinct modes of ATR activation orchestrated by Rad17 and Nbs1. Cell Rep 2013; 3:1651-62. PubMed
  • Birkelbach M, Ferraiolo N, Gheorghiu L, Pfäffle HN, Daly B, Ebright MI, Spencer C, O'Hara C, Whetstine JR, Benes CH, Sequist LV, Zou L, Dahm-Daphi J, Kachnic LA, Willers H. Detection of impaired homologous recombination repair in NSCLC cells and tissues. J Thorac Oncol 2013; 8:279-86. PubMed
  • Liu S, Ho CK, Ouyang J, Zou L. Nek1 kinase associates with ATR-ATRIP and primes ATR for efficient DNA damage signaling. Proc Natl Acad Sci U S A 2013; 110:2175-80. PubMed
  • Zou L. Four pillars of the S-phase checkpoint. Genes Dev 2013; 27:227-33. PubMed
  • Liu S, Song N, Zou L. The conserved C terminus of Claspin interacts with Rad9 and promotes rapid activation of Chk1. Cell Cycle 2012; 11:2711-6. PubMed
  • Centore RC, Yazinski SA, Tse A, Zou L. Spartan/C1orf124, a reader of PCNA ubiquitylation and a regulator of UV-induced DNA damage response. Mol Cell 2012; 46:625-35. PubMed
  • Flynn RL, Centore RC, O'Sullivan RJ, Rai R, Tse A, Songyang Z, Chang S, Karlseder J, Zou L. TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA. Nature 2011; 471:532-6. PubMed
  • Nakamura K, Kato A, Kobayashi J, Yanagihara H, Sakamoto S, Oliveira DV, Shimada M, Tauchi H, Suzuki H, Tashiro S, Zou L, Komatsu K. Regulation of Homologous Recombination by RNF20-Dependent H2B Ubiquitination. Mol Cell 2011; 41:515-28. PubMed
  • Flynn RL, Zou L. ATR: a master conductor of cellular responses to DNA replication stress. Trends Biochem Sci 2010. PubMed
  • Centore RC, Havens CG, Manning AL, Li JM, Flynn RL, Tse A, Jin J, Dyson NJ, Walter JC, Zou L. CRL4(Cdt2)-mediated destruction of the histone methyltransferase Set8 prevents premature chromatin compaction in S phase. Mol Cell 2010; 40:22-33. PubMed
  • Zou L. DNA repair: A protein giant in its entirety. Nature 2010; 467:667-8. PubMed
  • Flynn RL, Zou L. Oligonucleotide/oligosaccharide-binding fold proteins: a growing family of genome guardians. Crit Rev Biochem Mol Biol 2010; 45:266-75. PubMed
  • Huang M, Kim JM, Shiotani B, Yang K, Zou L, D'Andrea AD. The FANCM/FAAP24 complex is required for the DNA interstrand crosslink-induced checkpoint response. Mol Cell 2010; 39:259-68. PubMed
  • Sharma SV, Lee DY, Li B, Quinlan MP, Takahashi F, Maheswaran S, McDermott U, Azizian N, Zou L, Fischbach MA, Wong KK, Brandstetter K, Wittner B, Ramaswamy S, Classon M, Settleman J. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell 2010; 141:69-80. PubMed
  • Zou L. Checkpoint Mec-tivation comes in many flavors. Mol Cell 2009; 36:734-5. PubMed
  • Zhang J, Song YH, Brannigan BW, Wahrer DC, Schiripo TA, Harris PL, Haserlat SM, Ulkus LE, Shannon KM, Garber JE, Freedman ML, Henderson BE, Zou L, Sgroi DC, Haber DA, Bell DW. Prevalence and functional analysis of sequence variants in the ATR checkpoint mediator Claspin. Mol Cancer Res 2009; 7:1510-6. PubMed
  • Shiotani B,Zou L. Single-stranded DNA orchestrates an ATM-to-ATR switch at DNA breaks. Mol Cell 2009; 33:547-58. PubMed
  • Shiotani B,Zou L. ATR signaling at a glance. J Cell Sci 2009; 122:301-4. PubMed
  • Yang XH,Zou L. Dual functions of DNA replication forks in checkpoint signaling and PCNA ubiquitination. Cell Cycle 2009; 8:191-4. PubMed
  • Yang XH, Shiotani B, Classon M, Zou L. Chk1 and Claspin potentiate PCNA ubiquitination. Genes Dev 2008; 22:1147-52. PubMed
  • Yang XH, Zou L. Launching a ubiquitination cascade at DNA breaks. Proc Natl Acad Sci U S A 2007; 104:20645-6. PubMed
  • Zou L. Single- and double-stranded DNA: building a trigger of ATR-mediated DNA damage response. Genes Dev 2007; 21:879-85. PubMed
  • Wang X, Zou L, Lu T, Bao S, Hurov KE, Hittelman WN, Elledge SJ, Li L. Rad17 phosphorylation is required for claspin recruitment and chk1 activation in response to replication stress. Mol Cell 2006; 23:331-41. PubMed
  • Namiki Y, Zou L. ATRIP associates with replication protein A-coated ssDNA through multiple interactions. Proc Natl Acad Sci U S A 2006; 103:580-5. PubMed
  • Yang XH, Zou L. Checkpoint and coordinated cellular responses to DNA damage. Results Probl Cell Differ 2006; 42:65-92. PubMed
  • Yang XH, Zou L. Recruitment of ATR-ATRIP, Rad17, and 9-1-1 complexes to DNA damage. Methods Enzymol 2006; 409:118-31. PubMed
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