Kathy H.Y. Shair, PhD

Assistant Professor


Dr. Kathy H.Y. Shair

Contact

412-623-7717
Fax: 412-623-7715

1.8 Hillman Cancer Center

5117 Centre Avenue

Pittsburgh, PA 15213

Education

PhD in Virology, University of Cambridge (U.K.)

Research Summary

Cancer is a complex disease with multiple etiologies including host, environmental and microbial factors.  It is estimated that more than 15% of all human cancers are associated with a viral infection.  My laboratory studies how the γ-herpesvirus Epstein-Barr virus (EBV) causes cancer in epithelial and lymphoid cells.  EBV is the first discovered human tumor virus and new estimates associate it to nearly 200,000 new cancer cases per year worldwide. These include immuno-competent (nasopharyngeal carcinoma, gastric carcinoma, Hodgkin lymphoma, Burkitt lymphoma) and immuno-suppressed (post-transplant and AIDs-associated lymphomas) malignancies.  No approved prophylactic vaccine currently exists and more than 95% of adults by 35-40 years of age become latently infected.  The oncogenic and pro-migratory potential of the viral latent membrane proteins (LMP) 1 and 2 are well established but the molecular interplay between these viral proteins and their longitudinal effects on the tumor microenvironment are largely undetermined.  Importantly, metastatic nasopharyngeal carcinoma remains the most challenging phase of the disease. 

The goals of my laboratory are to study how virus-host interactions alter the biology of the infected cell and how modulation of the tumor microenvironment can contribute to cancer progression, maintenance and metastasis.  Using in vitro growth, migration and tumorigenicity assays, we dissect and link mechanistic changes in cell signaling and gene expression patterns to biological phenotypes.  These studies are extended to in vivo mouse models and clinical biopsies for assessing their biological relevance in whole organisms.  By studying how EBV modulates the infected cell and the surrounding tumor microenvironment, we can understand the molecular determinants of cancer development.  This knowledge will help us uncover how viruses contribute to the properties of the associated cancers and ultimately guide us in developing effective therapeutic strategies.

Research Lab Affiliation

Publications

Wasil L.R, Wei L, Chang C, Lan L and Shair K.H. (2015) Regulation of DNA Damage Signaling and Cell Death Responses by Epstein-Barr virus Latent Membrane Proteins (LMP) 1 and LMP2A in Nasopharyngeal Carcinoma Cells. J Virol. 89: 7612-7624. |  View Abstract

Shair, K. H; and Raab-Traub, N. (2012) Transcriptome changes induced by Epstein-Barr Virus LMP1 and LMP2A in transgenic lymphocytes and lymphoma. mBio. 3: e00288-e00312. |  View Abstract

Shair, K. H; Bendt, K. M; Edwards, R. H; Nielsen, J. N; Moore, D. T; and Raab-Traub, N. (2012) Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) and LMP2A function cooperatively to promote carcinoma development in a mouse carcinogenesis model. J Virol. 86: 5352-5365. |  View Abstract

Marquitz, A. R; Mathur, A; Shair, K. H; and Raab-Traub, N. (2012) Infection of Epstein-Barr virus in a gastric carcinoma cell line induces anchorage independence and global changes in gene expression. Proc Natl Acad Sci USA. 109: 9593-9598. |  View Abstract

Meckes, D. G., Jr; Shair, K. H; Marquitz, A. R; Kung, C. P; Edwards, R. H; and Raab-Traub, N. (2010) Human tumor virus utilizes exosomes for intercellular communication. Proc Natl Acad Sci USA. 47: 20370-20375. |  View Abstract

Shair, K. H; Schnegg, C. I; and Raab-Traub, N. (2009) Epstein-Barr virus latent membrane protein-1 effects on junctional plakoglobin and induction of a cadherin switch. Cancer Res. 14: 5734-5742. |  View Abstract

Shair, K. H; Schnegg, C. I; and Raab-Traub, N. (2008) EBV latent membrane protein 1 effects on plakoglobin, cell growth, and migration. Cancer Res. 17: 6997-7005. |  View Abstract