Photo of Elliott D. Kieff,  MD, PhD

Elliott D. Kieff, MD, PhD

Brigham And Women's Hospital

Brigham And Women's Hospital
Phone: (617) 525-4252
Fax: (617) 525-4257

Elliott D. Kieff, MD, PhD

Brigham And Women's Hospital


  • Harriet Ryan Albee Professor, Medicine, Harvard Medical School
  • Professor, Microbiology and Immunobiology, Harvard Medical School
  • Director, Infectious Diseases, Brigham And Women's Hospital

Research Abstract

This central objective of research program is to understand the mechanisms by which Epstein-Barr Virus causes human lymphoma, Hodgkin's Disease, nasopharyngeal cancer, gastric cancer, and other malignancies and to use that knowledge to devise new preventative, diagnostic, and therapeutic stategies.

Our current reserach has lead us to the conclusion that Epstein-Barr Virus uses aspects of the Notch and CD40 receptor signaling pathways to take control of cell growth and to increase cell survival. Given the role of Notch signaling in human T cell leukemia and of CD40 in lymphcyte growth regulation we are studying both the interaction of viral proteins with those pathways and the pathways themselves. Critical steps in these pathways can be exploited for the development of drug targets and such targets, especially NF-kB activation by LMP1 are being validated by genetic, biochemical, and screening studies.

Because of our interest in translational medicine, we are also studying the mechansisms by which EBV replicates and persists in cells and in humans. Current research in these areas involves mapping the interactions among EBV and cell proteins in replication and studies of the EBV perisitence proteins, EBNA1. Chemical screens for inhibitors of EBNA1 have identified several classes of inhibitors.


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  • 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
  • Ke L, Zhou H, Wang C, Xiong G, Xiang Y, Ling Y, Khabir A, Tsao GS, Zeng Y, Zeng M, Busson P, Kieff E, Guo X, Zhao B. Nasopharyngeal carcinoma super-enhancer-driven ETV6 correlates with prognosis. Proc Natl Acad Sci U S A 2017; 114:9683-9688. 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
  • Liang J, Zhou H, Gerdt C, Tan M, Colson T, Kaye KM, Kieff E, Zhao B. Epstein-Barr virus super-enhancer eRNAs are essential for MYC oncogene expression and lymphoblast proliferation. Proc Natl Acad Sci U S A 2016; 113:14121-14126. PubMed
  • Hu L, Lin Z, Wu Y, Dong J, Zhao B, Cheng Y, Huang P, Xu L, Xia T, Xiong D, Wang H, Li M, Guo L, Kieff E, Zeng Y, Zhong Q, Zeng M. Comprehensive profiling of EBV gene expression in nasopharyngeal carcinoma through paired-end transcriptome sequencing. Front Med 2016; 10:61-75. PubMed
  • Shen CL, Liu CD, You RI, Ching YH, Liang J, Ke L, Chen YL, Chen HC, Hsu HJ, Liou JW, Kieff E, Peng CW. Ribosome Protein L4 is essential for Epstein-Barr Virus Nuclear Antigen 1 function. Proc Natl Acad Sci U S A 2016; 113:2229-34. 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
  • Xiong D, Du Y, Wang HB, Zhao B, Zhang H, Li Y, Hu LJ, Cao JY, Zhong Q, Liu WL, Li MZ, Zhu XF, Tsao SW, Hutt-Fletcher LM, Song E, Zeng YX, Kieff E, Zeng MS. Nonmuscle myosin heavy chain IIA mediates Epstein-Barr virus infection of nasopharyngeal epithelial cells. Proc Natl Acad Sci U S A 2015; 112:11036-41. 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
  • Schmidt SC, Jiang S, Zhou H, Willox B, Holthaus AM, Kharchenko PV, Johannsen EC, Kieff E, Zhao B. Epstein-Barr virus nuclear antigen 3A partially coincides with EBNA3C genome-wide and is tethered to DNA through BATF complexes. Proc Natl Acad Sci U S A 2015; 112:554-9. PubMed
  • Verweij FJ, de Heus C, Kroeze S, Cai H, Kieff E, Piersma SR, Jimenez CR, Middeldorp JM, Pegtel DM. Exosomal sorting of the viral oncoprotein LMP1 is restrained by TRAF2 association at signalling endosomes. J Extracell Vesicles 2015; 4:26334. PubMed
  • Wang HB, Zhang H, Zhang JP, Li Y, Zhao B, Feng GK, Du Y, Xiong D, Zhong Q, Liu WL, Du H, Li MZ, Huang WL, Tsao SW, Hutt-Fletcher L, Zeng YX, Kieff E, Zeng MS. Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells. Nat Commun 2015; 6:6240. PubMed
  • Hadweh P, Habelhah H, Kieff E, Mosialos G, Hatzivassiliou E. The PP4R1 subunit of protein phosphatase PP4 targets TRAF2 and TRAF6 to mediate inhibition of NF-κB activation. Cell Signal 2014; 26:2730-7. 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
  • Lee EK, Kim SY, Noh KW, Joo EH, Zhao B, Kieff E, Kang MS. Small molecule inhibition of Epstein-Barr virus nuclear antigen-1 DNA binding activity interferes with replication and persistence of the viral genome. Antiviral Res 2014; 104:73-83. PubMed
  • Kim JE, Kim SY, Lim SY, Kieff E, Song YJ. Role of Ca2+/calmodulin-dependent kinase II-IRAK1 interaction in LMP1-induced NF-κB activation. Mol Cell Biol 2014; 34:325-34. PubMed
  • Jiang S, Willox B, Zhou H, Holthaus AM, Wang A, Shi TT, Maruo S, Kharchenko PV, Johannsen EC, Kieff E, Zhao B. Epstein-Barr virus nuclear antigen 3C binds to BATF/IRF4 or SPI1/IRF4 composite sites and recruits Sin3A to repress CDKN2A. Proc Natl Acad Sci U S A 2014; 111:421-6. PubMed
  • Chen YL, Liu CD, Cheng CP, Zhao B, Hsu HJ, Shen CL, Chiu SJ, Kieff E, Peng CW. Nucleolin is important for Epstein-Barr virus nuclear antigen 1-mediated episome binding, maintenance, and transcription. Proc Natl Acad Sci U S A 2014; 111:243-8. PubMed
  • Portal D, Zhou H, Zhao B, Kharchenko PV, Lowry E, Wong L, Quackenbush J, Holloway D, Jiang S, Lu Y, Kieff E. Epstein-Barr virus nuclear antigen leader protein localizes to promoters and enhancers with cell transcription factors and EBNA2. Proc Natl Acad Sci U S A 2013; 110:18537-42. PubMed
  • Liu CD, Cheng CP, Fang JS, Chen LC, Zhao B, Kieff E, Peng CW. Modulation of Epstein-Barr virus nuclear antigen 2-dependent transcription by protein arginine methyltransferase 5. Biochem Biophys Res Commun 2013; 430:1097-102. PubMed
  • Yasui T, Sakakibara-Yada K, Nishimura T, Morita K, Tada S, Mosialos G, Kieff E, Kikutani H. Protein kinase N1, a cell inhibitor of Akt kinase, has a central role in quality control of germinal center formation. Proc Natl Acad Sci U S A 2012; 109:21022-7. PubMed
  • Kim SY, Song KA, Kieff E, Kang MS. Small molecule and peptide-mediated inhibition of Epstein-Barr virus nuclear antigen 1 dimerization. Biochem Biophys Res Commun 2012; 424:251-6. PubMed
  • Rozenblatt-Rosen O, Deo RC, Padi M, Adelmant G, Calderwood MA, Rolland T, Grace M, Dricot A, Askenazi M, Tavares M, Pevzner SJ, Abderazzaq F, Byrdsong D, Carvunis AR, Chen AA, Cheng J, Correll M, Duarte M, Fan C, Feltkamp MC, Ficarro SB, Franchi R, Garg BK, Gulbahce N, Hao T, Holthaus AM, James R, Korkhin A, Litovchick L, Mar JC, Pak TR, Rabello S, Rubio R, Shen Y, Singh S, Spangle JM, Tasan M, Wanamaker S, Webber JT, Roecklein-Canfield J, Johannsen E, Barabási AL, Beroukhim R, Kieff E, Cusick ME, Hill DE, Münger K, Marto JA, Quackenbush J, Roth FP, DeCaprio JA, Vidal M. Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins. Nature 2012; 487:491-5. PubMed
  • Liu CD, Chen YL, Min YL, Zhao B, Cheng CP, Kang MS, Chiu SJ, Kieff E, Peng CW. The nuclear chaperone nucleophosmin escorts an Epstein-Barr Virus nuclear antigen to establish transcriptional cascades for latent infection in human B cells. PLoS Pathog. 2012; 8:e1003084. PubMed
  • Gulbahce N, Yan H, Dricot A, Padi M, Byrdsong D, Franchi R, Lee DS, Rozenblatt-Rosen O, Mar JC, Calderwood MA, Baldwin A, Zhao B, Santhanam B, Braun P, Simonis N, Huh KW, Hellner K, Grace M, Chen A, Rubio R, Marto JA, Christakis NA, Kieff E, Roth FP, Roecklein-Canfield J, Decaprio JA, Cusick ME, Quackenbush J, Hill DE, Münger K, Vidal M, Barabási AL. Viral perturbations of host networks reflect disease etiology. PLoS Comput. Biol. 2012; 8:e1002531. PubMed
  • Calderwood MA, Lee S, Holthaus AM, Blacklow SC, Kieff E, Johannsen E. Epstein-Barr virus nuclear protein 3C binds to the N-terminal (NTD) and beta trefoil domains (BTD) of RBP/CSL; only the NTD interaction is essential for lymphoblastoid cell growth. Virology 2011. PubMed
  • Kang MS, Lee EK, Soni V, Lewis TA, Koehler AN, Srinivasan V, Kieff E. Roscovitine inhibits EBNA1 serine 393 phosphorylation, nuclear localization, transcription, and episome maintenance. J Virol 2011; 85:2859-68. PubMed
  • Maruo S, Zhao B, Johannsen E, Kieff E, Zou J, Takada K. Epstein-Barr virus nuclear antigens 3C and 3A maintain lymphoblastoid cell growth by repressing p16INK4A and p14ARF expression. Proc Natl Acad Sci U S A 2011; 108:1919-24. PubMed
  • Zhao B, Mar JC, Maruo S, Lee S, Gewurz BE, Johannsen E, Holton K, Rubio R, Takada K, Quackenbush J, Kieff E. Epstein-Barr virus nuclear antigen 3C regulated genes in lymphoblastoid cell lines. Proc Natl Acad Sci U S A 2011; 108:337-42. 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
  • Lee S, Sakakibara S, Maruo S, Zhao B, Calderwood MA, Holthaus AM, Lai CY, Takada K, Kieff E, Johannsen E. Epstein-Barr virus nuclear protein 3C domains necessary for lymphoblastoid cell growth: interaction with RBP-Jkappa regulates TCL1. J Virol 2009; 83:12368-77. PubMed
  • Maruo S,Wu Y,Ito T,Kanda T,Kieff ED,Takada K. Epstein-Barr virus nuclear protein EBNA3C residues critical for maintaining lymphoblastoid cell growth. Proc Natl Acad Sci U S A 2009; 106:4419-24. PubMed
  • Choy E,Yelensky R,Bonakdar S,Plenge RM,Saxena R,De Jager PL,Shaw SY,Wolfish CS,Slavik JM,Cotsapas C,Rivas M,Dermitzakis ET,Cahir-McFarland E,Kieff E,Hafler D,Daly MJ,Altshuler D. Genetic analysis of human traits in vitro: drug response and gene expression in lymphoblastoid cell lines. PLoS Genet 2008; 4:e1000287. PubMed
  • Kang MS, Soni V, Bronson R, Kieff E. Epstein-Barr virus nuclear antigen 1 does not cause lymphoma in C57BL/6J mice. J Virol 2008; 82:4180-3. PubMed
  • Xing L, Kieff E. Epstein-Barr virus BHRF1 micro- and stable RNAs during latency III and after induction of replication. J Virol 2007; 81:9967-75. PubMed
  • Peng CW, Zhao B, Chen HC, Chou ML, Lai CY, Lin SZ, Hsu HY, Kieff E. Hsp72 up-regulates Epstein-Barr virus EBNALP coactivation with EBNA2. Blood 2007; 109:5447-54. PubMed
  • Calderwood MA, Venkatesan K, Xing L, Chase MR, Vazquez A, Holthaus AM, Ewence AE, Li N, Hirozane-Kishikawa T, Hill DE, Vidal M, Kieff E, Johannsen E. Epstein-Barr virus and virus human protein interaction maps. Proc Natl Acad Sci U S A 2007; 104:7606-11. PubMed
  • Hatzivassiliou EG, Kieff E, Mosialos G. Constitutive CD40 signaling phenocopies the transforming function of the Epstein-Barr virus oncoprotein LMP1 in vitro. Leuk Res 2006; 31:315-20. PubMed
  • Portal D, Rosendorff A, Kieff E. Epstein-Barr nuclear antigen leader protein coactivates transcription through interaction with histone deacetylase 4. Proc Natl Acad Sci U S A 2006; 103:19278-83. PubMed
  • Soni V, Yasui T, Cahir-McFarland E, Kieff E. LMP1 transmembrane domain 1 and 2 (TM1-2) FWLY mediates intermolecular interactions with TM3-6 to activate NF-kappaB. J Virol 2006; 80:10787-93. PubMed
  • Chen A, Zhao B, Kieff E, Aster JC, Wang F. EBNA-3B- and EBNA-3C-regulated cellular genes in Epstein-Barr virus-immortalized lymphoblastoid cell lines. J Virol 2006; 80:10139-50. PubMed
  • Rosendorff A, Sakakibara S, Lu S, Kieff E, Xuan Y, DiBacco A, Shi Y, Shi Y, Gill G. NXP-2 association with SUMO-2 depends on lysines required for transcriptional repression. Proc Natl Acad Sci U S A 2006; 103:5308-13. PubMed
  • Yuan J, Cahir-McFarland E, Zhao B, Kieff E. Virus and cell RNAs expressed during Epstein-Barr virus replication. J Virol 2006; 80:2548-65. PubMed
  • Zhao B, Maruo S, Cooper A, R Chase M, Johannsen E, Kieff E, Cahir-McFarland E. RNAs induced by Epstein-Barr virus nuclear antigen 2 in lymphoblastoid cell lines. Proc Natl Acad Sci U S A 2006; 103:1900-5. PubMed