Training:
• B.S., 1967: Reed College
• Ph.D., 1973: University of California, San Diego
• Postdoctoral, 1973-1975: University of Oregon Health Sciences Center Summary of the focus of the research of Dr. Roman:
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. Description and summary of research focus of the laboratory:
Dr. Roman's research is focused on the interaction between human papillomaviruses (HPVs) and their host epithelial cell, the keratinocyte. These viruses cause benign hyperproliferative disease (e.g. papillomas and warts) and contribute to the development of cervical cancer and some head and neck cancers. Dr. Roman's laboratory addresses a variety of aspects of viral pathogenesis, from intracellular interactions to the impact on intercellular interactions. The following specific areas are under investigation: 1. Regulation of the HPV life cycle by cellular proteins : The HPV life cycle is differentiation-dependent. A non-productive phase is seen in the undifferentiated cells where only minimal gene expression and viral DNA synthesis takes place. The productive phase occurs in the differentiated compartment of the stratified epithelium where all the viral genes are expressed and virus is produced. The Roman laboratory has identified two cellular transcription factors, CDP and YY1, which negatively regulate HPV promoters in undifferentiated cells but which are non-functional in differentiated cells. Recent work in the laboratory has shown that CDP also competes with the viral replication proteins to regulate initiation of viral DNA replication. These findings help explain why the virus must complete its life cycle in the differentiated compartment. 2. Altered regulation of cell cycle control and differentiation by HPVs : The fact that the productive phase of the HPV life cycle takes place in the differentiation compartment presents a paradox since cells must be in S phase to produce more viral DNA. Although the cells in this compartment have normally exited the cell cycle, in the presence of the HPV genome the cells allowing productive infection are in S phase. Hence HPV alters the normal proliferation:differentiation switch. To gain insight into one aspect of the complex interaction between HPVs and their host cell which might contribute to the different outcomes of infection, Dr. Roman's laboratory has focused on the activity of the E7 protein, a viral protein which binds the cellular retinoblastoma tumor suppressor protein. The laboratory has shown that the E7 protein increases the percentage of cells in S phase, delays differentiation, and affects cellular transcription perhaps, in part, through chromatin remodeling. Differences in the activities of an HPV E7 with high oncogenic potential and an HPV E7 with low oncogenic potential are under investigation. These studies should help distinguish viral activities required to complete the virus replication cycle from those giving the virus oncogenic potential. 3. HPV and angiogenesis, the recruitment of a blood supply. Both benign and malignant tumors have to induce new proliferation, migration, and differentiation of endothelial cells to provide the blood supply needed for a tumor to grow. The Roman laboratory, in collaboration with the Donner laboratory, has shown that the expression of two HPV proteins, E6 and E7, alters the profile of angiogenic factors secreted from keratinocytes and may thus contribute to the angiogenesis seen in both benign and malignant lesions. Ongoing experiments are pursuing the effect of this altered profile on the behavior of endothelial cells. Publications
Zhang, B., Li, P., Wang, E., Brahmi, Z., Dunn, K., Blum, J., and Roman, A. The E5 Protein of Human Papillomavirus Type 16 Perturbs MHC Class II Antigen Maturation in Human Foreskin Keratinocytes Treated with Interferon Gamma. Virology 310:100-108 (2003).
Toussaint-Smith, E., Donner, D., and Roman, A. Expression of Human Papillomavirus Type 16 E6 and E7 Oncoproteins in Human Foreskin Keratinocytes Is Sufficient to Alter the Expression of Angiogenic Factors. Oncogene 23: 2988-2995 (2004).
Zhang, B., Laribee, R.N., Klemsz, M. J., and Roman, A. The Human Papillomavirus Type 16 E7 Protein Increases Acetylation of Histone H3 in Human Foreskin Keratinocytes. Virology 329:189-198 (2004) .
Zhang, B., Chen, W., and Roman, A . The E7 Proteins of Low and High Risk Human Papillomaviruses Share the Ability to Target the pRB Family Member p130 for Degradation. Proc. Natl. Acad. Sci., U.S.A. 130:437-442 (2006).
Narahari, J., Fisk, J.C., Melendy, T., and Roman, A . Interactions of the Cellular CCAAT Displacement Protein and Human Papillomavirus E2 Protein with the Viral Origin of Replication Can Regulate DNA Replication, in press Virology (2006).
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