he Gewurz laboratory at the Brigham & Women’s Hospital and Harvard Medical School seeks a highly motivated postdoctoral fellow with a strong background in virology, molecular biology and/or immunology to join our research group in studies of Epstein-Barr virus pathogenesis. Please see our lab website for further details (gewurzlab.bwh.harvard.edu; https://www.hms.harvard.edu/dms/virology/fac/Gewurz.php)
Our lab focuses on host/pathogen interactions between EBV, a human herpesvirus, and B lymphocytes. EBV causes ~200,000 cancers each year worldwide. These include immune-suppression associated lymphomas, Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal and gastric carcinomas. We use cutting-edge CRISPR, genetic and proteomic approaches to study how EBV transforms primary human B-cells into immortalized lymphoblasts, to study the genetic switches that reprogram viral genome expression patterns at distinct stages of the EBV life cycle and across different human cancers, and study how the virus reprograms host metabolism pathways. A long-term goal is to identify host cell dependency factors and therapeutic targets that sensitize EBV-infected cells to eradication by chemical or immune therapy based-approaches.
New projects in the lab include:
CRISPR/Cas9 analysis of the EBV host/pathogen relationship. We are using CRISPR genetic analysis to perform genome-wide screens and focused genetic studies of host factors that control key stages of the EBV lifecycle. These include investigation of EBV-induced host dependency factors that enable transformed B-cell growth and survival, that reprogram EBV latency states, and that control the latency/lytic switch. We are also using CRISPR to identify mechanisms by which EBV evades key immune pathways, including subversion of the PDL1/PD1 T-cell immune checkpoint.
Defining key metabolic pathways that EBV rewires to support viral lytic replication versus B-cell transformation. We recently used multiplexed tandem-mass spectrometry to create proteomic maps of EBV lytic replication versus B-cell transformation. This approach identified EBV-induced cytosolic and mitochondrial pathways critical for primary human B-cell transformation. We are studying how EBV remodels these pathways, why they are required, and how they may be targeted therapeutically.
Our recent publications include:
Ersing I, Nobre L, Wang LW, Soday L, Ma Y, Paulo JA, Narita Y, Ashbaugh CW, Jiang C, Grayson NE, Kieff E, Gygi SP, Weekes MP, Gewurz BE. (2017) A Temporal Proteomic Map of Epstein-Barr Virus Lytic Replication in B Cells. Cell Rep. 2017 May 16;19(7): 1479-1493
Ma Y, Walsh MJ, Bernhardt K, Ashbaugh CW, Trudeau SJ, Ashbaugh IY, Jiang S, Jiang C, Zhao B, Root DE, Doench JG, Gewurz BE. (2017) CRISPR/Cas9 Screens Reveal Epstein-Barr Virus-Transformed B Cell Host Dependency Factors. Cell Host Microbe ; 21(5)
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. (2017) Mouse model of Epstein-Barr virus LMP1- and LMP2A-driven germinal center B-cell lymphoproliferative disease. Proc Natl Acad Sci;114(18): 4751-4756.
Epstein-Barr Virus LMP1-Mediated Oncogenicity. Wang LW, Jiang S, Gewurz BE. J Virol. 2017 Oct 13;91(21). pii: e01718-16.
The laboratory provides a robust training environment for postdocs and other trainees. We enjoy close relationships with the Brigham & Women’s Division of Infectious Disease, the Harvard Program in Virology, the Harvard Medical School Microbiology and Immunobiology Department, and with the Broad Institute of Harvard and MIT. These provide an excellent environment, including opportunities for collaboration, seminar series and core facilities.
Applicants are invited to send their curriculum vitae, summary of past work, and contact information for three references to Dr. Ben Gewurz.
The Brigham & Women’s hospital is an Equal Opportunity/Affirmative Action Employer