Research Groups

Cancer Molecular and Cell Biology

Research Interests and Description

Research Interests

Gene mutations and altered gene expression in cancer, detoxification gene polymorphisms and cancer predisposition, tumour cell invasion and metastasis, connective tissue gene expression, stromal cell - tumour interactions and tumour stem cells.

Description of Research

The interests of this Group span epidemiology to molecular lesions in cancer, with special reference to squamous cell carcinoma of the oesophagus. Oesophageal squamous cell carcinoma (OSSC) is one of the most common and devastating cancers in eastern and southern Africa.
Our epidemiological studies focus on the combined effects of genetic polymorphisms in the detoxification genes (cytochrome p450, glutathione-S-transferases, etc) and exposure to environmental mutagens and carcinogens to the risk of developing OSSC. The group will be doing genome-wide association studies to identify single nucleratide polymorphisms that confer increased risk to OSCC.
Human Papilloma Virus (HPV) DNA has been shown to be present in about 40% of South African tumour biopsies. We are investigating the role of the HPV E6 protein in the aetiology of this cancer and it’s effects on normal cellular genes. The role of the viral E6 and E7 proteins are being investigated using normal oesophageal epithelial cells transfected with these oncogenes.
Our interest in tumour cell invasion and metastasis centres around the degradation and remodeling of the extracellular connective tissue proteins. The role of tumour cells in the production of extracellular matrix proteins by normal stromal fibroblasts is being investigated by analysing the signal transduction pathways and the transcription factors regulating the expression of the type I collagen genes (one of the extracellular matrix proteins).
We developed a series of ajoene-based analogues that have been shown to be very effective in killing tumour cells in vitro. These analogues will be tested in animal models and studies are also underway to investigate the mode of action of these drugs.

Recent Publications

Torniainen, S., Parker, M.I., Holmberg, V., Lahtela, E., Dandara, C., Jarvela, I. 2009. Screening of variants for lactase persistence/non-persistence in populations from South Africa and Ghana. BMC Genetics 10,  1-5

van der Watt, P.J.,  Maske, C.P., Hendricks, D.T., Parker, M.I., Denny, L., Govender, D., Birrer, M.J., Leaner, V.D. 2009. The Karyopherin proteins, Crm1 and Karyopherin beta1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation. Int J Cancer. 124, 1829-1840

Wang, B., Khachigian, L.M., Birrer, M.J., Esau, L., Zhou, X., Parker, M.I., Hendricks, D.T. 2009. A key role for mediating and Maintaining GRO/CXCR2 proliferative signalling in oesophageal cancer. Mol. Cancer. Res. 5, 755-764

Abrahams, A., Mowla, S., Parker, M.I., Goding, C.R., Prince, S. 2008. UV Mediated Regulation of the Anti-Senescence Factor, Tbx2. J. Biol. Chem. 283, 2223-223

Davis, E., Teng, H., Bilican, B., Parker, M.I., Liu, B., Carriera, S., Goding, C.R., Prince, S. 2008. Ectopic Tbx2 expression results in polyploidy and cisplatin resistance. Oncogene, 27, 976-98

Donninger, H, Binder, A, Bohm, L, Parker, M.I. 2008. Differential Effects of Novel Tumour- Derived p53 Mutations on the Transformation of NIH 3T3 Cells. Biol. Chem 389, 57-67