Angelo L. DeLucia, Ph.D. Lab
My research studies are concerned with the understanding of how certain human papillomaviruses (HPVs) induce uterine cervical cancer, a major cause of women mortality worldwide. There are now known to be a number of other cancers associated with these viruses, such as head and neck tumors and various skin cancers.
Uncontrolled expression of papillomavirus oncogenes may be the spark to ignite the process toward carcinogenesis. Specific topics of my investigation include molecular analysis of how HPV gene expression is regulated by viral and cellular transcription factors. This analysis includes study of a complex regulatory region within the viral genome that contains the major promoter and enhancer elements for the viral oncogenes called the E6 and E7 genes.
Recently, in the process of exploring facets of the viral life cycle, we have discovered that a derivative of the plant lignan, nordihydroguaiaretic acid, has specific and potent inhibitory activity on HPV oncogene expression. Using these compounds, we should be able to reduce the levels of the viral E6 protein and thus interfere with a major route that leads to HPV- induced pre-cancerous and cancerous lesions.
These results, with others, suggest that it may be possible to manipulate the p53 tumor suppressor pathway to induce cell cycle growth arrest and subsequently apoptosis of pre-cancer and cancer cells treated with the plant lignans or in combination with other drugs. In order to determine that we are inducing senescence and/or apoptosis, we are currently measuring telomerase activity within drug-treated cells, cell cycle regulatory proteins, and apoptosis pathway activation.