In the broadest sense, my goal is to understand the biology and genetics of human cancer and aging. One of my primary interest is in how epithelial cells become immortal and subsequently malignant after infection with human papillomavirus (HPV). We are specifically focusing on the roles of genetic instability and telomerase activation in this process. I also am studying how telomere loss and other factors are involved in induction of cellular senescence. Specific areas of research are the following: 1) Defining the roles of telomere loss and telomerase dysfunction in keratinocyte aging and transformation; 2) Examining the regulation of cellular genes by HPV E6 and E7 during the process of infection and transformation; 3) Establishment and utilization of relevant model systems to study HPV-associated immortalization and malignant progression of human epithelial cells; 3) Defining mechanisms of genetic instability and determining the role of specific genomic alterations in the development of head and neck cancers; 5) Determining how the cell cycle inhibitor, p16INK4a, is regulated during telomere-independent senescence of human epithelial cells. It is hoped that these studies will increase our understanding of the processes that cause cancer and aging and will lead to better methods to prevent, diagnose, and treat human disease.