The Galloway lab is focused on the role that small DNA viruses play in cancer, including the high risk human papillomaviruses (HPV) in anogenital cancers, genus beta HPVs in squamous cell skin cancers, and the Merkel cell polyomavirus (MCPyV) in Merkel cell carcinomas. We have taken a broad based approach that includes mechanistic studies into how the viral oncoproteins contribute to neoplasia, and molecular epidemiologic studies into the natural history of viral infections and risk factors that are associated with the development of these cancers.
We have sought to determine how the HPV 16 E6 and E7 oncoproteins disrupt the cell cycle checkpoints that normally maintain genomic integrity, and how E6/E7 facilitates the immortalization of primary human cells in culture. In ongoing studies we are interested in how the E6 protein regulates expression of hTERT, the catalytic subunit of telomerase. HPV 16 E6 targets two isoforms of NFX1, promoting degradation of the NFX1-91 transcriptional repressor, and stabilizing the hTERT mRNA in concert with NFX1-123. We are also studying the genus beta E6 proteins, investigating the mechanisms by which they block apoptosis, and disrupt p53 activity by targeting the coactivator p300.
To aid in epidemiologic studies we have developed serologic assays to detect and characterize papillomavirus and polyomavirus-specific antibodies. The recent establishment of multiplex assays in our lab is affording a more comprehensive assessment of the prevalence of HPV and HPyV infections. In collaborative studies we are assessing HPV antibodies following natural infection in cohorts of young and mid-adult women, young men, and vaccinees (Dr. Laura Koutsky). We are determining whether markers of genus beta HPV infections predict the development of skin cancer in organ transplant recipients (Drs Margaret Madeleine, Dan Berg, Connie Davis and Peggy Porter), and similarly the association of MCPyV antibodies in Merkel cell carcinoma (Dr. Paul Nghiem).
In addition to viral oncogenes, we have studied the contributions of cellular oncogenes such as c-Myc and Ha-Ras to immortalization of human cells. In collaboration with Dr. Carla Grandori we have developed expression signatures for cells expressing these oncogenes and are examining how the RecQ helicases facilitate proliferation in c-Myc expressing cells and tumors.