Ph.D., University of Vermont - Cell Biology (1983)
Courses Currently Taught
BY312 Advanced Cell Biology
BY412 Molecular Biology Laboratory
BY422 Undergraduate Seminar
BY455 Cell and Molecular Biology of Cancer
My lab investigates how human papillomaviruses (HPV) contribute to cervical cancer. HPVs are small DNA tumor viruses that often cause warts on the skin and in the anogenital tract. There are over 100 different types of HPV, however, a small subset are termed "high risk" because infection with one of these types represents the major risk factor for cervical cancer. My research examines the interaction between HPVs and their natural target, the cervical epithelial cell. I study two related questions. (1) How does HPV perturb the normal function of epithelial cells in ways that can contribute to cancer? (2) How does the host respond to HPV infection? I am currently working on three related projects.
Activation of the NF-kB transcription factor by HPV. We have shown that expression of HPV-16 E6 and E7 genes (the major transforming genes of the virus) can activate NF-kB and stimulate expression of NF-kB-responsive genes. This is important because NF-kB is a master regulator of the immune response. NF-kB can also promote cell growth and survival, and contribute to malignant development. My lab is studying whether activation of NF-kB provides cervical cells with a survival advantage and increases immortalization by HPV. Current work focuses on 2 questions. (1) How do specific HPV genes activate NF-kB in cervical cells? (2) Does activation or inhibition of NF-kB alter immortalization by HPV? Our long term goal is to understand whether NF-kB is a target for therapy of HPV infection or cervical dysplasia.
Innate immune function of cervical cells from the transformation zone: The innate immune system of the cervix is the first line of defense against virus infection. The cervix contains 3 distinct regions; an ectocervix covered by squamous cells, an endocervix composed of secretory cells, and a narrow junction between these regions called the transformation zone. Almost all cervical cancers originate within the transformation zone, however, it is unclear why cells in this region are highly susceptible to cancer. We hypothesize that epithelial cells isolated from the transformation zone are less effective in production of cytokines that regulate innate immunity. We are using real time RT-PCR to analyze cytokine gene expression, and atomic force microscopy (in collaboration with Igor Sokolov of Clarkson) to examine cell-cell interactions that are important for the epithelial barrier. Furthermore, we are examining how HPV-16 E6 and E7 proteins alter growth and cytokine gene expression of cells from each region of the cervix.
The epidermal growth factor receptor (EGF-R) as a target for chemoprevention of cervical cancer. Immune compromised individuals (HIV-positive women and organ transplant patients) develop persistent HPV infections that progress to cervical dysplasia or cancer. These women would benefit from chemoprevention targeted to specific molecular pathways that are important in cervical carcinogenesis. The epidermal growth factor receptor (EGF-R) is a potential target. We found that inhibition of EGF-R function prevents immortalization of human cervical epithelial cells by HPV-16 E6 and E7, and stimulates expression of cytokines that enhance the innate immune response to HPV. Our long term goal is to access whether the EGF-R is an effective target for chemoprevention or therapy of cervical cancer in high risk patients. We are currently examining how inhibition of the EGF-R: (1) prevents immortalization of human cervical cells (2) stimulates expression of cytokines that mediate innate immunity, and (3) increases cell membrane rigidity and cell-cell adhesion, factors that contribute to the physical barrier of the cervical mucosa.
Publications (last 5 years)
Iyer, S., Gaikwad, R.M., Subba-Rao, Y., Woodworth, C.D., Sokolov, I. AFM Detects Differences in the Surface Brush of Normal and Cancerous Cervical Cells", Nature Nanotechnology 2009; 4:389-93.
Iyer, S., Woodworth, C.D., Gaikwad, R.M., Kievsky, Y.Y., Sokolov, I. Towards Nonspecific Detection of Malignant Cervical Cells with Fluorescent Silica Beads. Small. 2009;5:2277-2284
Iyer, S., Woodworth, C.D., Gaikwad, R.M., Kievsky, Y.Y., Sokolov, I. Fluorescent probes: Small 20/2009. Small 2009; in press
Pyeon D, Newton MA, Lambert PF, den Boon JA, Sengupta S, Marsit CJ, Woodworth CD, Connor JP, Haugen TH, Smith EM, Kelsey KT, Turek LP, Ahlquist P. Fundamental differences in cell cycle deregulation in human papillomavirus-positive and human papillomavirus-negative head/neck and cervical cancers. Cancer Res. 67: 4605-19 2007
Nees, M., Kusnezow, W., Woodworth, C.D. Microarrays: Small spots produce major advances in pharmacogenomics. In: Adjei, A. and Buolamwini, J.K, eds. Novel Anticancer Agents: Strategies for Discovery and Clinical Testing. Elsevier Press, New York (2006).
Sokolov, I., Iyer, S., and Woodworth, C.D. Recovery of elasticity of aged human epithelial cells in vitro. Nanomedicine: Nanotechnology, Biology, and Medicine. 2: 31-36 2006
Woodworth, C.D., Michael, E., Marker, D., Allen, S., Smith, L., & Nees, M., "Inhibition of the epidermal growth factor receptor increases expression of genes that stimulate inflammation, apoptosis and cell attachment," Mol. Cancer Ther., 4: 650-658 2005.
Berdyyeva, T.K., Woodworth, C.D., & Sokolov, I., "Human epithelial cells increase their rigidity with ageing in-vitro: direct measurements," Physics in Medicine and Biology, 50: 81-92 2005.
Berdyyeva, T.K., Woodworth, C.D., & Sokolov, I., "Visualization of cytoskeletal elements by the atomic force microscope," Ultramicroscopy, 102: 189-198 2005.
Students Currently Working in the Lab
- Katelynn Wilton, '11' "The Effect of the HPV-16 Oncoproteins, E6 and E7, on the Toll-Like receptors and Defensins of the Innate Immune System
- Krysta DeLuca, ‘11' "Effect of NF-kB on HPV-16 Upstream Regulatory Region Expression in Normal Cervical and Foreskin Cells"