Biology

Craig Woodworth
Professor
Medical and Professional School Advisor
Department of Biology
210 Science Center
Clarkson University
PO Box 5805
Potsdam, NY 13699-5805

E-mail: woodworth@clarkson.edu
Web site
Phone: 315-268-2391
Fax: 315-268-7118

Education
Ph.D., University of Vermont - Cell Biology (1983)

Courses Currently Taught
BY214 Genetics
BY312 Advanced Cell Biology
BY412 Molecular Biology Laboratory
BY422 Undergraduate Seminar
BY455 Cell and Molecular Biology of Cancer

Research Interests
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)
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.

Woodworth, C.D., Michael, E., Smith, L., Vijayachandra, K., Glick, A., Hennings, H., & Yuspa, S.H., "Strain-dependent differences in malignant conversion of mouse skin tumors is an inherent property of the epidermal keratinocyte," Carcinogenesis, 25: 1771-1778 2004.

Students Currently Working in the Lab

  • Erik Vandermark, PhD student / chemical biology, "Activation of NF- k B in Epithelial Cells Expressing Papillomavirus E6 and E7 Oncogenes"
  • Cynthia Schreiner '08, "Activation of NF-kB by Transient Expression of Human Papillomavirus Early Genes"
  • Michael Moses, ‘08’, “Does Inhibition of the EGF-R Block Growth and Induce Apoptosis Specifically in Cervical Cells that Express E6 and E7?”
  • Dan Stevens, '09', "Effects of EGF-R Inhibition on Cervical Cell Gene Expresion"
  • Courtney Grayson '09', "Effect of Stable Expression of HPV-16 E6 and E7 Proteins on NF-kB Activation"
  • Abdulmajid Mohammed, '09', "Inhibition of the Epidermal Growth Factor Receptor Prevents Immortalization of Human Cervical Cells"
  • Kristie Scalia, ‘10’, "Importance of the NF-kB Pathway in EGF-R Inhibitor-Induced Apoptosis"
  • Kelsie Timbie, ‘10’ “Developing a Biosensor for Cervical Cancer"