Differentiation-dependent replication of papillomaviruses and their role carcinogenesis

The major interest of our laboratory is to understand the differentiation-dependent replication of papillomaviruses and their role in carcinogenesis. Human papillomaviruses (HPV) are important human pathogens associated with benign and malignant neoplasias. HPV is the major risk factor in the development of cervical cancer. A major obstacle was once the inability to study the HPV life cycle in vitro. Using an organotypic (raft) culture system, my laboratory demonstrated for the first time the complete HPV life cycle in vitro, concomitant with the induction of a more complete differentiation program of the host tissue. This in vitro organotypic culture system allows us to use molecular biology, cell biology, and biochemistry to understand in detail the life cycle of HPV. We are analyzing the steps and mechanisms (viral and cellular) involved in viral DNA replication, gene expression, and oncogenesis. We are identifying and investigating the role of cofactors, such as other viruses and hormones, in the carcinogenic process. Additionally, we are using our system to support vaccine and therapeutic drug studies.