Research Groups
Cancer Molecular and Cell Biology
Research Interests and Description
Research Interests
Gene mutations and altered gene expression in cancer, detoxification gene polymorphisms in cancer predisposition, tumour cell invasion and metastasis, connective tissue - stromal cell - tumour interactions and tumour stem cells.
Description of Research
The interests of the 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 has embarked on genome-wide association studies to identify single nucleotide polymorphisms that confer increased susceptibility to OSCC.
Our studies have also shown that Human Papilloma Virus (HPV) DNA is present in about 40% of South African OSCC 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 is being investigated using normal oesophageal epithelial cells transfected with these oncogenes. We are also doing whole genome sequencing in order to identify other extraneous DNA sequences that may be present in tumour cells.
Our interest in tumour cell invasion and metastasis focuses on 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 are being tested in animal models and studies are also underway to investigate the mode of action of these drugs.
Recent Publications
- Dzobo, K.,Leaner , V.D., Parker, M.I. 2011. Feedback Regulation of the α 2(1) Collagen Gene via the MEK-ERK Signalling Pathway. IUBMB-Life In Press
Bye, H., Prescott, N.J., Matejcic, M., Lewis, C.M., Parker, M.I., Mathew, C.G.2011. Population-specific genetic associations with oesophageal squamous cell carcinoma in South Africa. Carcinogenesis 16, (Epub ahead of print) PubMed link
Kaschula, C.H, Hunter, R., Hassan, H.T, Stellenboom, N., Cotton, J, Xhai, X.Q., Parker, M.I.2011. Anti-proliferation Activity of Synthetic Ajoene Analogues in Cancer Cell Lines. Anticancer Agents Med Chem 11, 260-266 PubMed link
Abrahams, A., Parker, M.I., Prince, S. 2010. The T-box transcription factor Tbx2: Its role in development and possible implication in cancer. IUBMB-Life, 62, 92-102 PubMed link
Kaschula, C., Hunter, R., Parker, M.I. 2010. The anti-cancer activity of ajoene: the use of chemically synthesised stable analogues. Biofactors 36, 78-85
Li, D-P., Dandara, C., Parker, M.I. 2010. Genetic Polymorphisms in the Glutathione S-Transferase Genes (GSTM1, T1 & P1) and Oesophageal Cancer Susceptibility. BMC Genetics, 11, 47-56 PubMed link
