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Biology

In this Section

Craig Woodworth
Professor 
Department of Biology
210 Science Center
Clarkson University
PO Box 5805
Potsdam, NY 13699-5805

E-mail: woodworth@clarkson.edu
Web site: http://adweb.clarkson.edu/~cwoodwor/
 Phone: 315-268-2391
Fax: 315-268-7118

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

Courses Currently Taught
BY214 Genetics
BY419 Immunology
BY455 Cell and Molecular Biology of Cancer
BY480 Advanced Cell Biology


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)

Palantavida, S., Guz, N.V., Woodworth, C.D., Sokolov, I. Ultrabright fluorescent mesoporous silica nanoparticles for prescreening of cervical cancer. Nanomedicine, 2013, in press, 8:1255-62.

Iyer, S.K., Gaikwad. R,M,, Woodworth. C.D., Volkov, D.O., Sokolov, I. Physical Labeling of Papillomavirus-Infected, Immortal, and Cancerous Cervical Epithelial Cells Reveal Surface Changes at Immortal Stage. Cell Biochem Biophys. 2012, 63:109-16.

Vandermark, E.R., Deluca, K.A., Gardner, C.R., Marker, D.F., Schreiner, C.N., Strickland, D.A., Wilton, K.M., Mondal, S., Woodworth, C.D. Human papillomavirus type 16 E6 and E 7 proteins alter NF-kB in cultured cervical epithelial cells and inhibition of NF-kB promotes cell growth and immortalization. Virology, 2012, 425:53-60

Woodworth, C.D., Diefendorf, L.P., Jette, D.F., Mohammed, A., Moses, M.A., Searleman, S.A., Stevens, D.A. Wilton, K.M., Mondal, S. Inhibition of the epidermal growth factor receptor by erlotinib prevents immortalization of human cervical cells by human papillomavirus type 16. Virology, 2011, 421:19-27

Dokukin, M. E., Guz, N. V., Gaikwad, R. M., Woodworth, C. D., and Sokolov, I. Cell surface as fractal: Normal and cancerous cervical cells demonstrate different fractal behavior of surface adhesion maps at the nanoscale. Phys. Rev. Lett, 2011, 107:028101

Gaikwad, R. M., Dokukin, M. E., Iyer, K. S., Woodworth, C. D., Volkov, D.O., Sokolov, I. Detection of cancerous cervical cells using physical adhesion of fluorescent silica particles and centripetal force, Analyst  2011; 136:1502-6

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; 5


 Students Currently Working in the Lab  

  • Han Deng, PhD student, “ Immortalization of Cells from Different Anatomic Regions of the Cervix”
  • Joanina Gicobi, '15' “Apoptosis and Epithelial Marker Expression in Human Cervical Epithelial Cells”
  • Adam Presser,’15’ “Epithelial-Stromal Cell Interactions in Estrogen Response”
  • Scotlynne Rieder, ‘16’ “Estrogen Responsiveness of HPV-Immortalized Cervical Cells”
  • Tyler Hitchman, ‘16’ "Comparative Sensitivity to Apoptosis of Cells from Different Regions of the Cervix"
  • Grace Usher, '17' "Interaction of Gold Nanoparticles with Human Cervical Epithelial Cells"
  • Claire Englert, '17' Estrogen Responsiveness of HPV-Immortalized Cervical Cells"