Lineberger Professor of Cancer Research
Professor of Medicine and Microbiology & Immunology
Director Emeritus, UNC Lineberger Comprehensive Cancer Center, The University of North Carolina

32-000 Lineberger Comprehensive Cancer Center
Campus Box 7295
Chapel Hill, NC 27599-7295

919.966.5907

The Epstein-Barr virus (EBV) is associated with malignancies of lymphocytic and epithelial origin. EBV produces different infection states, cytolytic and latent, as well as cell immortalization, all of which are captured in cell lines, making them accessible to mechanistic studies. Currently, our research deals with viral latency, ubiquitin-proteasomal systems in cell signaling, interferon regulatory factors, invasion and metastasis, and antiviral drugs.
In EBV’s cytolytic infection cycle we are focusing on two EBV gene products. One encodes EBV’s sole protein kinase which phosphorylates other viral products, including the EBV DNA processivity factor used in viral replication and viral maturation proteins involved in egress of viral nucleocapids from the nucleus. We are also studying a recently discovered EBV-encoded deubiquitinating enzyme and its role in the viral cytolytic cycle.

In latent infection we study how the cell cycle serves as a global regulator of viral latent gene expression through its effects on the major nuclear proteins, EBNA1 and EBNA2. We also study mechanisms of cell immortalization and oncogenesis through EBV’s ability to stabilize and activate b-catenin via the ubiquitin system. IRF7 was discovered in this laboratory, and how EBV is able to mount and evade immune responses through the ability of EBV LMP1 to induce and activate IRF7, now recognized as the master regulator of Type 1 interferon responses, remains a principal focus. Finally we hold that EBV, in addition to being the etiologic agent for several malignancies, may also serve to promote tumor progression by the ability of its major oncoprotein, LMP1, to induce invasion, metastasis and angiogenic factors. Common to these areas is our emphasis on the role of tumor viruses in the ubiquitin-proteasomal system.

All trainees are encouraged to broaden their experience by also participating in the well known UNC-LCCC Postdoctoral Training Program to assist in progressing toward their career goals. Fellows will also present their work in progress at one of the weekly meetings of the extended Virology Faculty at UNC.

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