Dr. Roman's laboratory studies the pathobiology of human papillomaviruses (HPV). Aspects of her research include: regulation of the HPV life cycle by cellular proteins; altered regulation of cell cycle control and differentiation by HPV; and HPV and angiogenesis.
My research is directed at understanding the mechanism of human papillomaviruses pathogenesis. These viruses cause warts/papillomas, including sexually transmitted genital warts, and are risk factors for the development of lower genital tract cancers, such as cervical cancer. We study both low and high risk HPVs and we address how cellular proteins render the viral life cycle differentiation-dependent and how viral proteins alter intrinsic cellular behavior as well as cell:cell interactions.
Dr. Roman's laboratory is studying the mechanism of pathogenicity of human papillomaviruses (HPVs). Members of this family of viruses cause benign tumors (warts) and malignancies. In particular the Roman laboratory studies HPVs that infect the genital tract where these viruses cause the most prevalent viral sexually transmitted disease, genital warts, and act as cofactors in the development of cervical cancer. The research falls into two broad areas: regulation of the viral life cycle by cellular proteins and regulation of cellular growth control pathways by viral proteins. The HPV replication cycle is tightly linked to the state of differentiation of the keratinocyte, its target cell. In the basal layer there is little viral gene expression but as the cells differentiate the level of expression increases, the viral nucleic acid replicates, and virus is produced. Thus, one branch of research in the laboratory is directed at defining differentiation-dependent cellular factors which regulate human papillomavirus gene expression. This research is pertinent from two perspectives: a) it addresses the general question of how the interaction of a virus with a cell changes as the intracellular milieu changes due to differentiation, and b) it specifically addresses how the HPV replication cycle is regulated. The Roman laboratory has shown that there are two cellular proteins, CCAAT displacement protein and Yin Yang 1, which negatively regulate viral expression in undifferentiated cells but are inactive in differentiated cells. The laboratory is testing the hypothesis that these cellular proteins act as master switches to coordinately regulate amplification and encapsidation of viral genomes. Just as the cellular milieu affects the virus replication cycle, the virus affects the ability of the cells to exit the cell cycle and differentiate appropriately. Normally, the dividing cells are confined to the basal cell layer of the skin, and the differentiated cells are not dividing. However, the papillomaviruses have the ability to stimulate cells to reenter the cell cycle when they should no longer do so. The viruses require the differentiated cell for transcription of their genome, yet these same cells must be pushed to enter the cell cycle to produce proteins necessary for viral multiplication. With some HPVs, this induction of cell cycle is transient and leads only to the production of a wart while with other HPVs the induction is long-term and leads to the production of a malignant tumor. Therefore, in the other branch of our research the laboratory is defining activities in common between these two groups of viruses which allow them to replicate, i.e., entry into S phase, and activities distinct to one group of HPVs which render them oncogenic.
My research is directed at understanding the mechanism of human papillomaviruses pathogenesis. These viruses cause warts/papillomas, including sexually transmitted genital warts, and are risk factors for the development of lower genital tract cancers, such as cervical cancer. We study both low and high risk HPVs and we address how cellular proteins render the viral life cycle differentiation-dependent and how viral proteins alter intrinsic cellular behavior as well as cell:cell interactions.
