| RESEARCH PROGRAMME Thousands of proteins are expressed in a typical mammalian cell, of which as many as one third are now thought to contain covalently bound phosphate; indeed there is overwhelming evidence that reversible phosphorylation of proteins regulates most aspects of cell life. The activity of a phosphoprotein depends on the proportion of molecules in the phosphorylated or dephosphorylated state, which in turn depends on the relative activities of the interconverting enzymes, the protein kinases and phosphoprotein phosphatases. The research in my laboratory has aimed to achieve a greater understanding of the regulation of phosphorylation of key proteins, in particular with respect to cell proliferation, differentiation and the development of cancer and its reversal. The findings may provide insight into possible approaches which could be applied to the assessment and treatment of disorders involving abnormal cell growth and transformation. MAIN PROJECTS Witwatersrand University Funded by The National Cancer Association of South Africa, the South African Medical Research Council, the South African Foundation for Research Development, the H E Griffin Cancer Trust and the University of the Witwatersrand Research Committee. Protein phosphorylation and protein kinases in cells and tissues Regulation and function of phosphoprotein phosphatases Tumour suppressor proteins in cancer cells and tissues Receptors for growth factors and steroids in relation to cell proliferation and differentiation The role of ras and raf proteins in control of cell differentiation (in collaboration with Professor N Savage) Hormones, cell dynamics and the reversible phosphorylation of proteins (in collaboration with Dr D Gilbert) United Arab Emirates University Funded by the Terry Fox Cancer Research Fund and the UAEU Faculty of Medicine and Health Sciences Enzyme oscillations in a cell-free system. Temporal organization and control of protein kinases and phosphatases in leukaemic cells. Molecular profiling of leukaemic cells: proteomic analysis. Antisecretory and antiulcer activity of the new proton pump inhibitor, esomeprazole, and its mechanism of action. (in collaboration with Dr S. Bastaki) Effect of human chorionic gonadotrophin on reactivity of vascular smooth muscle from pregnancies complicated by hypertension and intrauterine growth retardation. (in collaboration with Professor M Ezimokhai) |
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