Post-doctoral Fellow, Brigham & Women's Hospital, Harvard Medical School

Brigham & Women's Hospital, Harvard Medical School

Categories:
  • Post Doctoral Position - Academic
Job Type/Arrangement:
  • Full Time
Description:

The Gewurz laboratory at the Brigham & Women’s Hospital, Harvard Medical School and the Broad Institute seeks a highly motivated postdoctoral fellow with a strong background in virology, molecular biology and/or immunology to join our NIH-funded research group in studies of Epstein-Barr virus pathogenesis and B-cell biology. 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 1) how EBV transforms primary human B-cells into immortalized lymphoblasts; 2) to study the genetic switches that reprogram viral genome expression patterns at distinct stages of the EBV life cycle and across different human cancers; 3) how the virus reprograms host metabolism pathways to support B-cell transformation versus lytic infection; 4) how EBV evades immune pathways to establish persistent infection. We are also interested in defining rare human immunodeficiencies that manifest by EBV-associated cancers. 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 innate and adaptive immune pathways during the latent or lytic lifecycles, and are using CRISPR targeting of the viral genome to define EBV lytic genes responsible for key phenotypes.

Defining key metabolic pathways that EBV rewires in infected B-cells. 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.

EBV oncoprotein LMP1 mimics signaling from CD40 receptors. We are using systematic CRISPR, ChIP-seq and proteomic approaches to define similarities and differences between B-cell CD40 and EBV LMP1 pathways.

Viral super-enhancers activate key host genes. Super-enhancers are particularly strong enhancers that establish cell identity and oncogenic states. We are using cutting-edge approaches to study how EBV nuclear antigens and EBV-activated host transcription factors nucleate these strong enhancers at key sites, such as the MYC locus.

The laboratory provides a robust and growing training environment for postdocs and other trainees. We are a highly collaborative lab that is located in the heart of the Harvard Medical School community in Boston. We enjoy close relationships with the Broad Institute of Harvard and MIT, the Harvard Program in Virology, the Harvard Medical School Microbiology and Immunobiology Departments, and the Harvard Medical School community. These provide an excellent environment, including many opportunities for collaboration, seminar series and excellent core facilities.

Our recent publications include:

Wang, L. et al. Epstein-Barr Virus Induced One-Carbon Metabolism Drives B-Cell Transformation. In revision, Cell Metabolism.

Jiang, C et al CRISPR/Cas9 Screens Reveal Multiple Layers of B-cell CD40 Regulation. In revision, Cell Reports.

Frost, T and Gewurz, BE. Epigenetic crossroads of the Epstein-Barr virus B-cell relationship (2018) Current Opinion in Virology

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)

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 Reports 2017 May 16;19(7): 1479-1493

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. PNAS ;114(18): 4751-4756.

Epstein-Barr Virus LMP1-Mediated Oncogenicity (2017) Wang LW, Jiang S, Gewurz BE. J Virology 2017 Oct 13;91(21). pii: e01718-16.

Gebre M, Nomburg JL, Gewurz BE. (2018) CRISPR-Cas9 Genetic Analysis of Virus-Host Interactions. Viruses. 10(2) pii: E55. doi: 10.3390/v10020055

Jiang S, Wang LW, Walsh MJ, Trudeau SJ, Gerdt C, Zhao B, Gewurz BE (2018) CRISPR/Cas9-Mediated Genome Editing in Epstein-Barr Virus-Transformed Lymphoblastoid B-Cell Lines. Curr Protoc Mol Biol. 121:31.12.1-31

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. (2018) Ephrin receptor A2 is an epithelial cell receptor for Epstein-Barr virus entry. Nature Microbiology. Feb;3(2)

Applicants are invited to send their curriculum vitae, summary of past work, and contact information for three references to Dr. Ben Gewurz at bgewurz@bwh.harvard.edu.

The Brigham & Women’s hospital is an Equal Opportunity/Affirmative Action Employer

Education Requirement:
PhD or MD degree
Salary:
Per NIH Payscale
Location:
Brigham & Women's Hospital
Infectious Disease and Department of Microbiology
181 Longwood Avenue
Boston , MA 02115
US
Contact:
Benjamin Gewurz, MD, PhD