The Robertson Lab


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Background

Since 1997 the Robertson lab has been dedicated to the study of virus-host interactions with a preference for viruses associated with cancers. Primarily, we study the two human gammaherpesviruses Epstein-Barr Virus (EBV) and Kaposi's Sarcoma herpesvirus (KSHV). We also study Hepatitis C Virus (HCV) as well as the infectious etiology for gastric cancer and ocular surface squamous cell neoplasia (OSSN).

Mechanisms of Oncogenesis by Gammaherpesvirus

We are investigating the mechanisms used by Epstein Barr Virus (EBV) and Kaposi's sarcoma Herpesvirus (KSHV) to induce cell mediated growth transformation. In particular, we are using genetic, genomic, proteomic and biochemical approaches to identify viral pathways involved in these cellular events to develop mechanistic models for transformation by gammaherpesviruses.

EBV and KSHV are gammaherpesviruses which are associated with a number of human malignancies. KSHV is associated with Kaposi's sarcoma (KS), Multicentric Castleman's disease and body cavity based lymphomas also referred to as pleural effusion lymphomas. EBV causes infectious mononucleosis (IM), Hodgkin's Lymphoma, Burkitt's Lymphoma, nasopharyngeal and breast carcinomas. Typically, infection by either of these viruses is asymptomatic. In fact, EBV infection is very common as greater than 90% of adults are seropositive for EBV. KSHV infection is less common in the general population, although there is a higher percentage of infected individuals in specific geographic regions and in immunocompromised individuals. After infection, these viruses can cause an initial lytic infection where infected cells actively produce viral progeny. Afterwards, the virus enters a quiescent latent phase, stably establishing itself for the lifetime of the host.

Kaposi's sarcoma became popular in the public in the early 90s as one of the most apparent AIDS defining illnesses. In 1994 Chang and Moore identified KSHV as the causative agent associated with Kaposi's sarcoma. KSHV was identified as the second human oncogenic herpesvirus with collinear homology to EBV and infects human B-cells and endothelial cells. However, the mechanism of KSHV mediated oncogenesis is not well characterized. The KSHV Latency-Associated Nuclear Antigen (LANA) is the most consistently detected antigen in KSHV-infected cells of disease origin and is the hallmark of KSHV genome persistence. LANA tethers the KSHV genome to histones, and modulates cell cycle, transcription, apoptosis, and chromatin remodeling.


 


The Robertson Lab, 202 A-B Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104 (215)746-0114