Description of Research Expertise
Research Interests
Mechanisms of Oncogenesis by Gammaherpesvirus.
Key words: oncogenesis, viruses and cancer, viral oncology, Tumor Virology, Gene therapy, Kaposi's Sarcoma, Epstein-Barr Virus, Lymphoproliferative disease, Lymphomas, Microbiome and Cancer.
Description of Research
Epstein-Barr virus (EBV) and Kaposi's sarcoma associated herpesvirus (KSHV) are associated with a number of human malignancies. These include Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's lymphoma, breast carcinoma, Kaposi's sarcoma and body cavity based lymphoma. We are investigating the fundamental mechanisms utilized by these gammaherpesviruses to induce cell mediated growth transformation. We are using genetics, genomics and biochemical approaches to establish unknown pathways involved in these cellular events and attempting to develop models that explain how gammaherpesviruses establish transformation in human cells.
EBV infects human B-lymphocytes and is the etiological agent of infectious mononucleosis. In vitro EBV efficiently growth transforms primary B-lymphocytes. Studies have demonstrated that only a subset of the viral latent genes is essential for EBV mediated transformation. One such gene is the EBV nuclear antigen EBNA3C. EBNA3C is a large nuclear transcription factor involved in modulating transcription activated by a cellular repressor RBP-Jkappa and other transcription factors. We are interested in other related functions of EBNA3C through its interactions with a number of other cellular molecules. Screens to identify other cellular targets have identified a number of interesting targets associated with EBNA3C. These molecules are involved in cell division, metastasis, apoptosis, cell cycle regulation and regulation of protein degradation. We are currently pursuing a number of these molecules in an effort to demonstrate their biochemical, structural and functional relevance in human cancers.
KSHV is the second human oncogenic herpesvirus, associated with Kaposi's sarcoma (KS) and pleural effusion lymphomas (PELs) or body cavity based lymphomas (BCBLs). KSHV also belongs to the human gammaherpesvirus family with collinear homology to EBV. KSHV infects human B-cells and endothelial cells. The mechanism of KSHV mediated oncogenesis is not understood. Our laboratory is involved in the elucidation of the mechanisms by which KSHV persists and establishes persistent infection in the associated human cancers.
Rotation Projects
Positions available. Please contact Dr. Robertson via mail.
Lab personnel:
Jason Knight, MSTP Candidate
Subhash Verma, Postdoctoral Fellow
Ke Lan, Postdoctoral Fellow
Masano Murukami, Postdoctoral Fellow
Sumit Borah, Research Specialist
Daniel Kuppers, Research Specialist
Selected Publications
Banerjee S, Wei Z, Tan F, Peck KN, Shih N, Feldman M, Rebbeck TR, Alwine JC, Robertson ES.: Distinct microbiological signatures associated with triple negative breast cancer. Scientific Reports : 2015.
Abhik Saha, Hem C. Jha, Santosh K. Upadhyay, and Erle S. Robertson: Epigenetic silencing of tumor suppressor genes during in vitro Epstein-Barr virus infection. Proc Natl Acad Sci U S A 112 ( 37): E5199-207,2015.
Sun Z1, Jha HC1, Robertson ES2.: Bub1 in Complex with LANA Recruits PCNA To Regulate Kaposi's Sarcoma-Associated Herpesvirus Latent Replication and DNA Translesion Synthesis. J. Virology 89 (20): 2015.
Jha HC1, Shukla SK1, Lu J1, Aj MP1, Banerjee S1, Robertson ES1.: Dissecting the contribution of EBNA3C domains important for EBV-induced B-cell growth and proliferation. Oncotarget : 2015.
Gandhi J, Gaur N, Khera L, Kaul R, Robertson ES.: COX-2 induces lytic reactivation of EBV through PGE2 by modulating the EP receptor signaling pathway. Virology 484 : 1-14,2015.
Dzeng RK1, Jha HC1, Lu J1, Saha A1, Banerjee S1, Robertson ES2.: Small molecule growth inhibitors of human oncogenic gammaherpesvirus infected B-cells. Mol Oncol. 9 (2): 365–376,2015.
Baldwin DA, Feldman M, Alwine JC, Robertson ES.: Metagenomic assay for identification of microbial pathogens in tumor tissues. MBio 5 (5): 2014.
Banerjee S1, Lu J1, Cai Q2, Sun Z1, Jha HC1, Robertson ES1.: EBNA3C augments Pim-1 mediated phosphorylation and degradation of p21 to promote B-cell proliferation. PLoS Pathogens : 2014.
Sun Z, Xiao B, Jha HC, Lu J, Banerjee S, Robertson ES.: Kaposi's sarcoma-associated herpesvirus-encoded LANA can induce chromosomal instability through targeted degradation of the mitotic checkpoint kinase Bub1. J. Virology 88 (13): 2014.
Lu J1, Jha HC, Verma SC, Sun Z, Banerjee S, Dzeng R, Robertson ES.: Kaposi's sarcoma-associated herpesvirus-encoded LANA contributes to viral latent replication by activating phosphorylation of survivin. J. Virology 88 (8): 4204-4217,2014.
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Academic Contact Information
201E Johnson Pavilion
3610 Hamilton Walk
Philadelphia,
PA
19104
Phone: 215-746-0114