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David Meek obtained his PhD from the University of Glasgow in 1983 where he studied the regulation of gluconeogenesis by protein phosphorylation and by the novel metabolic regulator, fructose 2,6-bisphosphate, in Hugh Nimmo’s lab. He subsequently won an MRC Retraining Fellowship in Recombinant DNA Technology which he took up at the Department of Molecular Biology in the University of Edinburgh. Here he studied the regulation of expression of RNA polymerase in E. coli under the direction of Richard Hayward. David then carried out four years’ post-doctoral study at the Salk Institute in San Diego, funded by a fellowship from the American Cancer Society. He worked under the direction of Walter Eckhart and pioneered our understanding of the regulation of the p53 tumour suppressor by post-translational modification. David returned to the UK in 1990 having obtained a prestigious MRC Senior Fellowship to work in the MRC Protein Phosphorylation Unit at Dundee. Here he developed his research programme as an independent researcher with the enthusiastic support of Prof Sir Philip Cohen and Prof Sir David Lane. During this time David made a number of key contributions to our understanding of p53 regulation and opened up an area of study that was subsequently to attract intensive international interest and effort. In 1993 he moved to the fledgeling Biomedical Research Centre at Ninewells Hospital where he continued to develop his interest in the p53 pathway and maintain his collaborative association with basic scientists and clinicians. He continued to be supported here by the MRC fellowship which he held until 2001. In 1996 he jointly organised and hosted the 8th International p53 workshop at Dundee, together with David Lane and Peter Hall. This event brought together the leading international pioneers of p53 research at what is now the major international p53 conference series: it also underpinned the collective focus, strength and success of p53 research across Dundee. At the beginning of the new millennium, David pioneered our understanding of the regulation of MDM2, the key regulator of p53, by post-translational modification. This gave rise to an international effort in this area and provided a major focus of his research activities for the next 6-7 years. Together with David Lane, he instituted the first International MDM2 Workshop at Dundee which was to become a major two-yearly international event held at various prestigious centres across the globe. David continues his interest in the p53 network where his efforts have focused on its role in human cancer and its potential for reactivation as a therapeutic strategy to combat cancer.
The p53 tumour suppressor protein is a potent transcription factor which stimulates the expression of a host of genes involved in growth arrest, apoptosis, DNA repair, metabolism, stem cell renewal, inhibition of angiogenesis, invasion and metastasis. p53 also is able to repress the expression of a different set of genes including those involved in mediating or stimulating cell division. These events are thought to mediate p53 tumour suppression function. Loss of p53 activity in developing cancers occurs through various mechanisms, including mutation of the TP53 gene itself (encoding p53), and leads to loss of tumour suppressor function. Additionally, several commonly occurring TP53 mutations give rise to so-called “gain-of-function” mutant p53 proteins that have acquired new activities thought to help drive aggressive cancer behaviour.
Aims of our Research
• To understand the molecular basis of the signalling mechanisms (post-translational modifications and protein: protein interactions) that regulate the p53 response.
• To determine whether the signalling events regulating p53 are modulated or changed during tumour development in a manner that would inhibit the ability of the p53 network to carry out its protective function of eliminating genetically damaged cells.
• To explore specific mechanistic and signalling interactions with a view to determining their potential as targets for novel therapeutic intervention in the treatment of cancer
David Meek teaches, and has taught previously, on several courses in the Medical School including BMSc (bachelor of medical science); MB ChB student-selected components; the MRes Cancer Biology (post-graduate) course; and the BSc Biomedical Sciences course (Schools of Life Sciences, and Medicine). He additionally runs a level 3 BSc (Biomedical Science) module entitled: "Cell proliferation and survival mechanisms underlying disease" and a post-graduate MRes Cancer Biology module entitled: "Scientific Method".
At the postgraduate level, he has trained 5 MRes students, 1 MSc (by research) student and 11 PhD, students. He currently has 5 PhD students under his supervision. David is the Deputy Chair of the Research Postgraduate Committee in the Medical School. He is also a leading player in several other committees that oversee teaching quality, organisation and funding in the university.