Megan E. Spurgeon, PhD

Research Title:  The Long-Term Effectiveness of Estrogen Receptor Alpha Antagonists as Potential Treatment for HPV-associated Cervical Cancer

Project Summary: Dr. Megan Spurgeon’s research focused on two areas of research in the Lambert lab. The first regards estrogen receptor alpha (ERa) as a therapeutic target in in human papillomavirus (HPV)-driven cervical carcinogenesis.  Prior studies in the lab had demonstrated that when treated with exogenous estrogen, HPV16 transgenic mice frequently develop cervical cancer, that this carcinogenesis depended upon ERa, and that ERa antagonists could cause regression of these cancers after only one month treatment.  Megan pursued a study to learn if treatment with ERa antagonists was capable of eliminating all cervical cancer progenitor cells in this mouse model.  She learned that in mice that were released from the one month treatment with the ERa antagonists, cancers frequently recurred over the ensuing three month observation period, even in the absence of re-exposure to exogenous estrogen, indicating that residual cancer cells must remain following treatment with the one month treatment with ERa antagonist and that they no longer depend upon exogenous estrogen to grow as cancers.  She carried out further studies to show that these recurrent cancers are again responsive to ERa antagonists, and that extending the original ERa antagonist treatment from 1 to 4 months prevented recurrence from arising in a majority of mice. These studies provide evidence that ERa antagonists not only are effective in treating cervical cancer but also in preventing recurrence of cervical cancers. A manuscript describing that study is currently under review (in revision).  Related to these studies, Megan is involved in gene expression profiling studies to further understand the underlying role of estrogen and its receptor, ERa, in cervical carcinogenesis. In a second project, Megan has initiated studies on a new human tumor virus, Merkel Cell Carcinoma-associated Polyomavirus (MCV), which is associated with 80% of Merkel cell carcinomas, a relatively rare skin disease. She has taken a two-pronged approach to the study of MCV building on the expertise of the Lambert lab in developing in vitro and in vivo models for HPVs. First, making use of 3D organotypic cultures of human keratinocytes, which support the full epithelial cell differentiation program resulting in the formation of stratified squamous epithelium, Megan discovered that MCV infects and propagates itself in human keratinocytes. This finding is the first to measure MCV infectivity in a natural host cell type. She is now further characterizing this new model for MCV infection.  Secondly Megan generated MCV transgenic mice in which she has directed expression of the putative MCV oncogenes to epithelial cells.  These MCV transgenic mice show acute epithelial hyperplasia and dysplasia.  Studies ongoing will look at whether this leads to neoplastic progression and to characterize any tumors that do arise in these mice.