Hibma Lab Research
Several viruses are known to cause cancer. Much of our current understanding of the cellular processes of cancer comes from the study of DNA tumour viruses. One such virus is the human papillomavirus (HPV). This virus is fascinating as some types cause benign proliferation of skin cells (for example skin warts) whereas other ‘high-risk’ types cause cancer. We are particularly interested in HPV type 16, which causes cervical cancer because of its health relevance for New Zealanders and especially Maori who have an extremely high incidence of this disease.
Invasiveness is a defining step in malignancy and any treatment that blocks invasion and spread of cancer cells would drastically reduce cancer mortality. Human papillomavirus provided us with an extraordinary opportunity to explore tumour cell invasion and to identify ways to treat it. We have shown that these viruses can disrupt a cellular protein that is critical in the suppression of invasion that occurs in normal healthy cells. We have also shown that this may impact on the immune cells in the skin that are important in initiating the immune response to the viral infection. Our current research focus is to identify how the virus affects the suppression of invasion and to develop treatments to block it. Our interests extend to understanding how the regulation of this cellular pathway influences the immune response to the virus. This research is designed to increase our understanding of the fundamental processes and treatment of tumour invasiveness and will impact not only on cervical cancer but also on other cancer types.
More than one quarter of the deaths in New Zealand are attributed to cancer. Cancer mortality is predicted to increase as mortality due to infectious disease continues to decline. It is imperative that the prevention and treatment of cancer is improved so that the country’s disease burden in the 21st century can be reduced.
(See downloads section below for PDFs)
Burn, C. and Hibma, M. Human papillomavirus virus-like particles and their potential as gene delivery vectors in the skin. New Zealand Medical Journal. 124:1-1 (2011).
Rose, S., Baker, M., Hibma, M., and Lawton, B. Predictors of intent to vaccinate against HPV/cervical cancer: a survey of 769 Maori and non-Maori parents. New Zealand Medical Journal. In press (2011).
Cheng Mee Leong, John Doorbar, Ingo Nindl, Han-Seung Yoon and Merilyn Hibma. Deregulation of E-cadherin by human papillomavirus is not confined to high-risk, cancer-causing types. Brit. J. Dermatol. 163: 1253-1263 (2010)
Rose SB, Lawton BA, Lanumata T, Hibma M, Baker MG. HPV/cervical cancer vaccination: Parental preferences on age, place and information needs. J Prim Health Care, 2:190-198 (2010).
Cheng Mee Leong, John Doorbar, Ingo Nindl, Han-Seung Yoon and Merilyn H. Hibma. Loss of epidermal Langerhans cells occurs in human papillomavirus α, γ and μ but not β genus infections. J. Invest. Dermatol. 130:472-480 (2010).
Dana Westphal, Elizabeth C. Ledgerwood, Joel D.A. Tyndall, Merilyn H. Hibma, Norihito Ueda, Stephen B. Fleming, and Andrew A. Mercer. The orf virus inhibitor of apoptosis functions in a Bcl-2-like manner, binding and neutralizing a set of BH3-only proteins and active Bax. Apoptosis, 14, 1317-1330 (2009).
Merilyn H. Hibma, Nicola C. Real, Anna Wiles, Deirdre Dobson-Le, Brett R. Dix, David Wynford-Thomas, Antony W. Braithwaite and Janice A. Royds. Increased apoptosis and reduced replication efficiency of the E3 region-modified dl309 adenovirus in cancer cells. Virus Res. 145:112-120 (2009).
Heinemann, L., Woodfield, L., Amer, M. and Hibma, M. Effective induction of type 1 helper IgG2a and cytotoxic T cell responses in mice following immunisation with human papillomavirus type 16 E2 in MF59. Viral Immunology, 21, 225-233 (2008).
Leong, C-M., Tarbotton, J. and Hibma, M. Self-applied treatment of a persistent plantar wart with 5% imiquimod cream. New Zealand Medical Journal, 120:1-1 (2007).
Westphal, D., Ledgerwood, E., Hibma, M., Fleming, S., Whelan, E. and Mercer, A. A novel Bcl-2-like inhibitor of apoptosis is encoded by the parapoxvirus, Orf virus. Journal of Virology, 83:7178-7188 (2007).
Dillon, S., Sasagawa, T., Crawford, A., Prestidge, J., Inder, M., Jerram, J., Mercer, A. and Hibma, M. Resolution of cervical dysplasia is associated with T cell proliferative responses to human papillomavirus type 16 E2. Journal of General Virology, 88:803-813 (2007).
Janice Royds, Merilyn Hibma, Brett R. Dix, Lynne Hananeia, I. Alasdair Russell, Anna Wiles, David Wynford-Thomas and Antony W. Braithwaite. p53 promotes adenoviral replication and increases late viral gene expression. Oncogene, 25:1509-1520 (2006).
Justin Shields and Merilyn Hibma. The constitutive expression of HPV16 E6 in HCT116 cells leads to a reduction in E-cadherin levels that cannot be counteracted by chemicals Indole-3-carbinol or Tamoxifen. New Zealand Medical Journal, 118:1-1 (2005).
Leong, C.M., and Hibma, M.H. A flow cytometry-based assay for the measurement of protein regulation of E-cadherin-mediateted adhesion. Journal of Immunological Methods, 302: 116-124 (2005).
Heinemann, L., Dillon, S., Crawford, A. and Hibma, M.H. Quantification of virally infected cells by flow cytometry following viral challenge in a mouse infection model. Journal of Virological Methods, 117:9-18 (2004).
Middleton, K., Southern, S., Peh, W., Griffin, H., Sotlar, K., El-Sherif, A., Morris, L., Seth, R., Hibma, M.H., Jenkins, D., Coleman, N., and Doorbar, J. Organisation of the human papillomavirus productive cycle during neoplastic progression provides a basis for the selection of markers for cervical screening. Journal of Virology, 77:10186-10201 (2003).
Matthews, K., Leong, C.M., Baxter, L., Inglis, E., Yun, K., Backstrom, B., Doorbar, J. and Hibma, M.H. Depletion of Langerhans cells in human papillomavirus type 16 infected skin is associated with E6 mediated down regulation of E-cadherin. Journal of Virology, 77:8378-8385 (2003).
Edwards, S., Dix, B., Myers, C., Dobson-Le, D., Huschtscha, L., Hibma, M., Royds, J. and Braithwaite, A. Evidence that replication of the antitumor adenovirus ONYX-015 is not controlled by the p53 and p14ARF tumor suppressor genes. Journal of Virology, 76:12483-12490 (2002).