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Shair Lab



Principal Investigator

Kathy H.Y. Shair, PhD

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Location

1.8 Hillman Cancer Center

5117 Centre Avenue

Pittsburgh, PA 15213

Research Description

Epstein-Barr virus (EBV) is an oncogenic γ-herpesvirus that is associated with human epithelial and B cell malignancies.  The Shair lab studies the molecular mechanisms of cancer induced by EBV latency with the purpose of defining how these mechanisms contribute to the oncogenic and metastatic properties of EBV-associated diseases.  

The oncogenic and cancer-associated properties of the viral latent membrane proteins (LMP) 1 and LMP2A are well established however, particularly for epithelial infections, the molecular interplay between these viral proteins and their function in EBV pathogenesis are largely undetermined.  Furthermore, metastatic nasopharyngeal carcinoma remains the most challenging condition to treat.

EBV-associated cancers have a characteristic latent gene expression pattern.  EBV immortalizes primary B cells and LMP1 is critically required for this process.  In comparison, expression of LMP1 or LMP2A proteins in epithelial cells can promote growth and migratory properties, often resulting in increased tumor-forming potential in cell lines transplanted as xenografts in mice.  Our studies in transgenic mice have shown that LMP2A complements LMP1 in tumor models, promoting carcinogen-induced carcinoma incidence and can also induce unique gene expression changes in B cells that are only apparent in the presence of both proteins.  This provided the first in vivo evidence that LMP1 and LMP2A functionally co-operate to result in unique phenotypes.  A major goal of the Shair lab is to elucidate mechanisms of LMP1 and LMP2A co-operation and to determine which interacting cellular pathways are most relevant to tumorigenesis and metastasis.

Current projects:

1. EBV mechanisms of genomic instability: This project investigates LMP1 and LMP2A mechanisms in nasopharyngeal carcinoma and pediatric post-transplant lymphoproliferative disease 

2. Determinants of EBV pathogenesis and persistence in epithelial infections: This project involves developing polarized infection models to study EBV pathogenesis in respiratory epithelia

3. Small animal models of EBV oncogenesis: This project involves testing EBV oncogenic proteins in transgenic and humanized mice

4. Discovery of cancer biomarkers: This project screens human sera for EBV biomarkers

Dr. Shair conducts research through the University of Pittsburgh Cancer Institute (UPCI) Cancer Virology Program at the Hillman Cancer Center located in Shadyside.  Learn more>

Members

Amit Kumar - Postdoctoral Associate

Elizabeth Caves – Undergraduate researcher

Akhil Reddy – Undergraduate researcher