Photo of Ben Gewurz,  MD, PhD

Ben Gewurz, MD, PhD

Brigham And Women's Hospital

Brigham And Women's Hospital
Phone: (617) 525-4282

Ben Gewurz, MD, PhD

Brigham And Women's Hospital


  • Associate Chair, Harvard Virology Program, Medicine, Harvard Medical School
  • Associate Physician, Medicine/Infectious Disease, Brigham And Women's Hospital
  • Associate Chair, Virology Program, Harvard Medical School


Research Abstract

Please visit our lab website:

Our research focuses on EBV-mediated oncogenesis. We use CRISPR genetic and proteomic techniques to interrogate how EBV reprograms key B-cell growth, survival, metabolic and immune-evasion pathways.

EBV is an oncogenic gamma-herpesvirus that persistently infects >95% of adults worldwide. EBV is associated with multiple human malignancies, with nearly 200,000 cancers attributable to EBV each year worldwide. These include Burkitt lymphoma, Hodgkin lymphoma, HIV-associated lymphomas, post-transplant lymphoproliferative diseases, and immune-senescence-associated lymphomas. EBV is also causally associated with epithelial malignancies, including nasopharyngeal carcinoma and gastric carcinoma. EBV's association with cancer is an outgrowth of its relationship with host cells. Upon infection of primary B lymphocytes, EBV enters a state of viral latency, but is hardly quiescent. Rather, EBV expresses oncogenic membrane proteins, transcription factors and microRNAs that efficiently transform resting B-lymphocytes into rapidly growing lymphoblasts. In vitro, EBV converts primary resting B lymphocytes into immortalized lymphoblastoid cell lines (LCLs), which provide an excellent tissue culture model for studies of EBV latency proteins and lymphoproliferative disorders.

Current research includes the following areas:

1) CRISPR/Cas9 screens to identify novel synthetic lethal targets in EBV-transformed B-cells. We are using CRISPR-based genetic approaches to identify key oncogenic strategies that support EBV-driven immortalized B-cell growth, including how the virus evades tumor repressor responses. These vulnerabilities may be exploited to rationally target the growth and survival of EBV-transformed B-cells.


The EBV oncoprotein Latent Membrane Protein 1 (LMP1) mimics CD40 signaling to potently activate the canonical and non-canonical NF-kB, MAP kinase, and IRF7 pathways. LMP1-mediated NF-kB activation is essential for EBV-mediated B-cell transformation, and for the growth and survival of transformed cells. We use genetic and proteomic approaches to study LMP1 signaling from the assembly of plasma membrane signalosomes through the activation of NF-kB transcription factor complexes. Likewise, we use next-generation sequencing-based technologies, including ChIP-seq. We are using CRISPR/Cas9, RNAi, ChiP-seq, and mass-spectrometry-based proteomic approaches to characterize how LMP1 constitutively activates NF-kB pathways. We are also comparing LMP1 and CD40-mediated NF-kB target gene regulation in B-cells.


We are using whole cell mass spectrometry-based approaches to probe the EBV/host relationship during B-cell transformation versus lytic replication. This unbiased, systematic approach promises identify novel viral strategies central to EBV biology, including EBV subversion of host growth and survival pathways, metabolic pathways, innate and adaptive immune pathways. Likewise, we are identifying whole proteome changes that accompany EBV-mediated primary B-cell transformation.


We are conducting whole exome and immunologic studies oF individuals with persistent active EBV infection and EBV-associated B-cell malignancy. These studies promise to identify key aspects of the host immune response required to control EBV lytic and latent infection.


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  • Wang C, Zhou H, Xue Y, Liang J, Narita Y, Gerdt C, Zheng AY, Jiang R, Trudeau S, Peng CW, Gewurz B, Zhao B. Epstein-Barr Virus Nuclear Antigen Leader protein co-activates EP300. J Virol 2018. PubMed
  • Gebre M, Nomburg JL, Gewurz BE. CRISPR-Cas9 Genetic Analysis of Virus-Host Interactions. Viruses 2018. PubMed
  • Wang LW, Trudeau SJ, Wang C, Gerdt C, Jiang S, Zhao B, Gewurz BE. Modulating Gene Expression in Epstein-Barr Virus (EBV)-Positive B Cell Lines with CRISPRa and CRISPRi. Curr Protoc Mol Biol 2018; 121:31.13.1-31.13.18. PubMed
  • Jiang S, Wang LW, Walsh MJ, Trudeau SJ, Gerdt C, Zhao B, Gewurz BE. CRISPR/Cas9-Mediated Genome Editing in Epstein-Barr Virus-Transformed Lymphoblastoid B-Cell Lines. Curr Protoc Mol Biol 2018; 121:31.12.1-31.12.23. PubMed
  • Zhang H, Li Y, Wang HB, Zhang A, Chen ML, Fang ZX, Dong XD, Li SB, Du Y, Xiong D, He JY, Li MZ, Liu YM, Zhou AJ, Zhong Q, Zeng YX, Kieff E, Zhang Z, Gewurz BE, Zhao B, Zeng MS. Ephrin receptor A2 is an epithelial cell receptor for Epstein-Barr virus entry. Nat Microbiol 2018. PubMed
  • Jiang S, Zhou H, Liang J, Gerdt C, Wang C, Ke L, Schmidt SCS, Narita Y, Ma Y, Wang S, Colson T, Gewurz B, Li G, Kieff E, Zhao B. The Epstein-Barr Virus Regulome in Lymphoblastoid Cells. Cell Host Microbe 2017; 22:561-573.e4. PubMed
  • Wang LW, Jiang S, Gewurz BE. Epstein-Barr Virus LMP1 Mediated Oncogenicity. J Virol 2017. PubMed
  • Ma Y, Walsh MJ, Bernhardt K, Ashbaugh CW, Trudeau SJ, Ashbaugh IY, Jiang S, Jiang C, Zhao B, Root DE, Doench JG, Gewurz BE. CRISPR/Cas9 Screens Reveal Epstein-Barr Virus-Transformed B Cell Host Dependency Factors. Cell Host Microbe 2017; 21:580-591.e7. PubMed
  • Minamitani T, Ma Y, Zhou H, Kida H, Tsai CY, Obana M, Okuzaki D, Fujio Y, Kumanogoh A, Zhao B, Kikutani H, Kieff E, Gewurz BE, Yasui T. Mouse model of Epstein-Barr virus LMP1- and LMP2A-driven germinal center B-cell lymphoproliferative disease. Proc Natl Acad Sci U S A 2017. PubMed
  • Blondel CJ, Park JS, Hubbard TP, Pacheco AR, Kuehl CJ, Walsh MJ, Davis BM, Gewurz BE, Doench JG, Waldor MK. CRISPR/Cas9 Screens Reveal Requirements for Host Cell Sulfation and Fucosylation in Bacterial Type III Secretion System-Mediated Cytotoxicity. Cell Host Microbe 2016; 20:226-37. PubMed
  • Hunter JE, Butterworth JA, Zhao B, Sellier H, Campbell KJ, Thomas HD, Bacon CM, Cockell SJ, Gewurz BE, Perkins ND. The NF-κB subunit c-Rel regulates Bach2 tumour suppressor expression in B-cell lymphoma. Oncogene 2016; 35:3476-84. PubMed
  • Minamitani T, Yasui T, Ma Y, Zhou H, Okuzaki D, Tsai CY, Sakakibara S, Gewurz BE, Kieff E, Kikutani H. Evasion of affinity-based selection in germinal centers by Epstein-Barr virus LMP2A. Proc Natl Acad Sci U S A 2015; 112:11612-7. PubMed
  • Greenfeld H, Takasaki K, Walsh MJ, Ersing I, Bernhardt K, Ma Y, Fu B, Ashbaugh CW, Cabo J, Mollo SB, Zhou H, Li S, Gewurz BE. TRAF1 Coordinates Polyubiquitin Signaling to Enhance Epstein-Barr Virus LMP1-Mediated Growth and Survival Pathway Activation. PLoS Pathog. 2015; 11:e1004890. PubMed
  • Zhou H, Schmidt SC, Jiang S, Willox B, Bernhardt K, Liang J, Johannsen EC, Kharchenko P, Gewurz BE, Kieff E, Zhao B. Epstein-Barr virus oncoprotein super-enhancers control B cell growth. Cell Host Microbe 2015; 17:205-16. PubMed
  • Zhao B, Barrera LA, Ersing I, Willox B, Schmidt SC, Greenfeld H, Zhou H, Mollo SB, Shi TT, Takasaki K, Jiang S, Cahir-McFarland E, Kellis M, Bulyk ML, Kieff E, Gewurz BE. The NF-κB genomic landscape in lymphoblastoid B cells. Cell Rep 2014; 8:1595-606. PubMed
  • Iannetti A, Ledoux AC, Tudhope SJ, Sellier H, Zhao B, Mowla S, Moore A, Hummerich H, Gewurz BE, Cockell SJ, Jat PS, Willmore E, Perkins ND. Regulation of p53 and Rb links the alternative NF-κB pathway to EZH2 expression and cell senescence. PLoS Genet. 2014; 10:e1004642. PubMed
  • Zhou X, Massol RH, Nakamura F, Chen X, Gewurz BE, Davis BM, Lencer WI, Waldor MK. Remodeling of the intestinal brush border underlies adhesion and virulence of an enteric pathogen. MBio 2014. PubMed
  • Ersing I, Bernhardt K, Gewurz BE. NF-κB and IRF7 pathway activation by Epstein-Barr virus Latent Membrane Protein 1. Viruses 2013; 5:1587-606. PubMed
  • Zhou X, Gewurz BE, Ritchie JM, Takasaki K, Greenfeld H, Kieff E, Davis BM, Waldor MK. A Vibrio parahaemolyticus T3SS effector mediates pathogenesis by independently enabling intestinal colonization and inhibiting TAK1 activation. Cell Rep 2013; 3:1690-702. PubMed
  • Gewurz BE, Towfic F, Mar JC, Shinners NP, Takasaki K, Zhao B, Cahir-McFarland ED, Quackenbush J, Xavier RJ, Kieff E. Genome-wide siRNA screen for mediators of NF-κB activation. Proc Natl Acad Sci U S A 2012; 109:2467-72. PubMed
  • Gewurz BE, Mar JC, Padi M, Zhao B, Shinners NP, Takasaki K, Bedoya E, Zou JY, Cahir-McFarland E, Quackenbush J, Kieff E. Canonical NF-kappaB activation is essential for Epstein-Barr virus latent membrane protein 1 TES2/CTAR2 gene regulation. J Virol 2011; 85:6764-73. PubMed
  • Boehm D, Gewurz BE, Kieff E, Cahir-McFarland E. Epstein-Barr latent membrane protein 1 transformation site 2 activates NF-kappaB in the absence of NF-kappaB essential modifier residues 133-224 or 373-419. Proc Natl Acad Sci U S A 2010; 107:18103-8. PubMed
  • Song YJ, Izumi KM, Shinners NP, Gewurz BE, Kieff E. IRF7 activation by Epstein-Barr virus latent membrane protein 1 requires localization at activation sites and TRAF6, but not TRAF2 or TRAF3. Proc Natl Acad Sci U S A 2008; 105:18448-53. PubMed
  • Gewurz BE, Harper JW. DNA-damage control: Claspin destruction turns off the checkpoint. Curr Biol 2006; 16:R932-4. PubMed
  • Gewurz BE, Ploegh HL, Tortorella D. US2, a human cytomegalovirus-encoded type I membrane protein, contains a non-cleavable amino-terminal signal peptide. J Biol Chem 2002; 277:11306-13. PubMed
  • Gewurz BE, Gaudet R, Tortorella D, Wang EW, Ploegh HL. Virus subversion of immunity: a structural perspective. Curr Opin Immunol 2001; 13:442-50. PubMed
  • Gewurz BE, Gaudet R, Tortorella D, Wang EW, Ploegh HL, Wiley DC. Antigen presentation subverted: Structure of the human cytomegalovirus protein US2 bound to the class I molecule HLA-A2. Proc Natl Acad Sci U S A 2001; 98:6794-9. PubMed
  • Gewurz BE, Wang EW, Tortorella D, Schust DJ, Ploegh HL. Human cytomegalovirus US2 endoplasmic reticulum-lumenal domain dictates association with major histocompatibility complex class I in a locus-specific manner. J Virol 2001; 75:5197-204. PubMed
  • McAdam AJ, Gewurz BE, Farkash EA, Sharpe AH. Either B7 costimulation or IL-2 can elicit generation of primary alloreactive CTL. J Immunol 2000; 165:3088-93. PubMed
  • Tortorella D, Gewurz BE, Furman MH, Schust DJ, Ploegh HL. Viral subversion of the immune system. Annu Rev Immunol 2000; 18:861-926. PubMed
  • McAdam AJ, Farkash EA, Gewurz BE, Sharpe AH. B7 costimulation is critical for antibody class switching and CD8(+) cytotoxic T-lymphocyte generation in the host response to vesicular stomatitis virus. J Virol 2000; 74:203-8. PubMed