School of Life Sciences

My early career was spent as a chemical analyst in the petrochemical industry andsubsequently followed with studied toward a BSc degree in Biochemistry and Medical Cell Biology at the University of Liverpool (First call honours). After a period at Astra Zeneca (formerly ICI Diagnostics) as research scientist I went on to complete a PhD in molecular biology at the University of Manchester. A lectureship at Liverpool John Moores was then followed by appointment to the University of Keele where most of my academic career and research has been performed. I am Professor of Human Genomics and basic science lead for the Clinical and Diagnostic Medicine theme. In addition I also hold an Associate Investigator position at NIH (Bethesda Washington DC) and am also on the editorial board of several journals.

As a PI at the University of Keele, I have a long-standing collaboration with clinical endocrinologists and my research initially focused on the molecular aspects of pituitary tumorigenesis and on epigenetic changes in these tumours. More recently my work has included studies of fetal epigenetics (see below). For many of our published studies, they are or have been regarded as novel, “first past the post” findings and reports. While early studies adopted a candidate gene approach more recent studies have employed whole genome analyses. Thus, in 2004 (Bahar et al Molecular Endocrinology) we identified, from the pituitary, a novel pro-apoptotic gene of previous unknown function on the basis of its differential methylation. More recently (Dudley et al., Molecular Cancer Research 2008), using siRNA mediated reversal of epigenetic change in a murine model system we identified, in an array-based (genome-wide) approach, numerous novel silenced genes in these cells and many of these gene were also found to be subject to epigenetic silencing in primary human pituitary tumours. These studies were subsequently extended (Revill et al., Endocrine Related Cancer 2009) to focus on an imprinted gene, neuronatin, with tumour suppressor properties. Our more recent studies Al-Azzawi H et al., 2011 Endocrinology have used a technique termed “pharmacological unmasking”. These studies have been successfully employed to restore endogenous, but silenced, receptor gene expression in tumour cells. The re-expressed receptor then augments ligand induced apoptosis. Other ongoing studies, in collaboration with other international researchers is focused on characterising histone modifications as part of the “histone code”. These studies attract multiple invitations to group members to present at and also to chair international meetings and symposia.

Fetal Epigenetics

A highly productive and rewarding area of research has also been possible through our Fetal Epigenetic Group

Membership of this multidisciplinary group has capitalised on our expertise in epigenetics, and in particular unbiased whole-genome analyses in relation to cancer related and cancer predisposition genes. Our focus, as a group has been centred around nutrition and in particular the role of folic acid and its metabolites on the fetal epigenome. Our success, built on an enthusiastic team approach has resulted in our research attracting funding from several sources including the WCRF. Our publications have generated considerable interest within both the scientific community and the media. We were particularly heartened that a review published by us in the BJOG, (Nafee TM et al, 2008) was the second most frequently cited paper of 2008. More recently, and attracting world-wide attention we identified from more than 27,000 genome-wide site a panel of genes associated with fetal birth weight. In these cases changes were associated with methylation changes (Fryer AA, et al., [2010 and 2011]) Epigenetics.

The pages of the Fetal Epigenetics Group