Persistent human papillomavirus (HPV) infection can ultimately lead to cervical cancer. Our research explores the molecular and cellular changes that accompany HPV-mediated transformation and in vitro progression of human epithelial cells, with an emphasis on HPV-induced alterations in signal transduction pathways associated with cell proliferation (epidermal growth factor pathway) as well as inhibition of cell growth (transforming growth factor-beta pathway).
In particular, gene expression profiling techniques (microarrays) are used to define molecular signatures associated with early and late stages of HPV-mediated transformation and alterations in growth factor responses. These studies have led to the finding that overexpression of the homeodomain transcription factor Six1 in HPV16-immortalized human keratinocytes promotes differentiation resistance, epithelial-mesenchymal transition (EMT), and malignant conversion.
We also conduct studies in women to explore environmental and genetic determinants of HPV persistence with the goal of identifying “biomarkers” that will predict risk of a cervical premalignant and malignant disease. Studies also are aimed at identifying a biological basis for the increased risk of cervical cancer in African American women compared to European American women. We recently discovered that high risk HPV persists longer in African American women than European American women of college age. Our research is supported by the National Institute for Minority Health and Health Disparities (5P20MD001770).
Bachelor of Science
University of Puget Sound
Doctor of Philosophy
Cell Biology, 1980-1983
Washington University School of Medicine
National Cancer Institute
- Xu, H., Pirisi, L., and Creek, K.E.: Six1 overexpression at early stages of HPV16-mediated transformation of human keratinocytes promotes differentiation resistance and EMT. Virology 474: 144-153, 2015.
- Banister, C.E., Messersmith, A.R., Cai, B., Spiryda L.B., Glover S.H., Pirisi L., and Creek K.E.: Disparity in high risk HPV persistence between African American and European American women of college age. Journal of Infectious Diseases, Advance Access published August 12, 2014.
- Weige, C.C., Birtwistle, M.R., Mallick, H., Yi, N., Berrong, Z., Cloessner, E., Duff, K., Tidwell, J., Clendenning, M., Wilkerson, B., Farrell, C., Bunz, F., Ji, H., Shtutman, M., Creek, K.E., Banister, C.E., and Buckhaults, P.: Transcriptomes and shRNA suppressors in a TP53 allele-specific model of early-onset colon cancer in African Americans. Mol. Cancer Res. 12: 1029-1041, 2014.
- Xu, H., Zhang, Y., Altomare, D., Pena, M.M., Wan, F., Pirisi, L., and Creek, K.E.: Six1 promotes epithelial-mesenchymal transition and malignant conversion in human papillomavirus type 16-immortalized human keratinocytes. Carcinogenesis 35:1379-1388, 2014.
- Altomare, D., Velidandla, R., Pirisi, L., and Creek, K.E.: Resistance to growth inhibition by TGF-beta is associated with partial loss of Smad signaling in the absence of alterations of Smad protein levels during in vitro progression of HPV16-immortalized human keratinocytes. BMC Cancer 13:424, 2013.
- Kowli, S., Velidandla, R., Creek, K.E. and Pirisi, L.: TGF-beta regulation of gene expression at early and late stages of HPV16-mediated transformation of human keratinocytes. Virol. 447:63-73, 2013.
- Banister, C.E., Messersmith, A.R., Chakraborty, H., Wang, Y., Spiryda, L.B., Glover, S.H., Pirisi, L., and Creek, K.E.: HPV prevalence at enrollment and baseline results from the Carolina Women’s Care Study, a longitudinal study of HPV persistence in women of college age. International J. Women’s Health 5:379-388, 2013.
More selected publications
- Chen, Y., Pirisi, L., and Creek, K.E.: Ski protein levels increase during in vitro progression of HPV16-immortalized human keratinocytes and in cervical cancer. Virol. 444:100-108, 2013.
- Hypes, M.K., Pirisi, L., and Creek, K.E.: Mechanisms of decreased expression of transforming growth factor-beta receptor type I at late stages of HPV16-mediated transformation. Cancer Letters 282: 177-186, 2009.
- Wan, F., Miao, X., Quraishi, I., Kennedy, V., Creek, K.E., and Pirisi, L.: Gene expression changes during HPV-mediated carcinogenesis: A comparison between an in vitro cell model and cervical cancer. Int. J. Cancer 123: 32-40, 2008.
- Bheda, A., Creek, K.E., and Pirisi, L.: Loss of p53 induces epidermal growth factor receptor promoter activity in normal human keratinocytes. Oncogene 27: 4315-4323, 2008.
- Baldwin, A. Hypes, M.K., Pirisi, L., and Creek, K.E.: NFI is an essential positive transcription factor for human papillomavirus type 16 early gene expression. The Open Virology Journal 1: 33-38, 2007.
- Baldwin, A., Pirisi, L. and Creek, K.E.: NFI-Ski interactions mediate transforming growth factor-beta modulation of human papillomavirus type 16 early gene expression. J. Virol. 78: 3953-3964, 2004.
- Akerman, G.S., Tolleson, W.H., Brown, K.L., Zyzak, L.L., Mourateva, E., Engin, T.S.W., Basaraba, A., Coker, A.L., Creek, K.E. and Pirisi, L.: Human papillomavirus type 16 E6 and E7 cooperate to increase epidermal growth factor receptor (EGFR) mRNA levels, overcoming mechanisms by which excessive EGFR signaling shortens the life span of normal human keratinocytes. Cancer Res. 61: 3837-3843, 2001
- Borger, D.R., Mi, Y., Geslani, G., Zyzak, L.L., Batova, A., Engin, T.S.W., Pirisi, L. and Creek, K.E.: Retinoic acid resistance at late stages of human papillomavirus type 16-mediated transformation of human keratinocytes arises despite intact retinoid signaling and is due to a loss of sensitivity to transforming growth factor-beta. Virology 270: 397-407, 2000.
- Mi, Y., Borger, D.R., Fernandes, P.R., Pirisi, L. and Creek, K.E.: Loss of transforming growth factor-beta (TGF-beta) receptor type I mediates TGF-beta resistance in human papillomavirus type 16 transformed human keratinocytes at late stages of in vitro progression Virology 270: 408-416, 2000.
- Xu, X., Kelleher, K.F., Liao, J., Creek, K.E. and Pirisi, L.: Unique carboxyl terminal sequences of wild-type and alternatively spliced variant forms of transforming growth factor-alpha precursors mediate specific interactions with ErbB4 and ErbB2. Oncogene 19: 3172-3181, 2000.