School of Life Sciences
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My early career was spent as a chemical analyst in the petrochemical industry and subsequently 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 In addition I have completed sabbatical research and extended visits to US institutions that include the Thomas Jefferson, Philadelphia, NIH (Bethesda Washington DC) and Cedars Sinai, Los Angeles. I am also on the editorial boards, as Senior Associate Editor for Endocrine Diabetes and Metabolism Case Reports and Scientific Editor for the journals Endocrine Related Cancer, Neuroendocrinology and Endocrine Pathology.
My PhD training was carried out at the University of Manchester examining the expression and molecular biology of the POMC gene and glucocorticoid receptor regulation. As a PI at the University of Keele my research has focused primarily on the molecular biology of pituitary tumours and more recently on epigenetic changes in bladder tumours and rheumatoid arthritis. In a multi-institution collaboration we have also investigate genome-wide changes to the fetal epigenome and in particular in the context of folic acid supplementation and folate metabolism. Our first study of methylation mediated silencing in pituitary tumours described epigenetic silencing of the CDKN2A gene and numerous other laboratories have since replicated these findings. Many of our published studies are regarded as novel and “first past the post”. While early studies adopted candidate gene approaches more recent studies have employed whole genome analysis. As example, we were the first to employ whole genome amplification to perform a high-density allelotyping of pituitary adenomas and in a subsequent study to employ this new-found knowledge to a retrospective cohort of recurrent pituitary tumours. In 2004 we identified, from the pituitary, a novel pro-apoptotic gene of previous unknown function on the basis of its differential methylation. More recently our laboratory (Dudley et al., 2008), used a siRNA approach to reverse epigenetic change in a murine pituitary cell line model and thereby identify, in an expression 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. Our laboratory is also the first to described genome-wide DNA BeadArray analysis of each of the major pituitary adenoma subtype (Duong et al., 2012) and to show the effects of the so name epidrugs on gene and pituitary receptor expression (Al-Azzawi et al., Yacqub-Usman et al., 2012a, 2012b, 2013).These findings and reports over the past several years have led to numerous invitations to speak and also to chair symposia both nationally and internationally.
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.
Selected Publications
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2013. Epigenome-wide profiling identifies significant differences in DNA methylation between matched-pairs of T- and B-lymphocytes from healthy individuals. Epigenetics, vol. 8(11). link>
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2013. GENOME-WIDE DNA METHYLATION PROFILING IN T CELLS FROM PATIENTS WITH RHEUMATOID ARTHRITIS. RHEUMATOLOGY (vol. 52, p. 143). link>
Full Publications List show
Journal Articles
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2013. Epigenome-wide profiling identifies significant differences in DNA methylation between matched-pairs of T- and B-lymphocytes from healthy individuals. Epigenetics, vol. 8(11). link>
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2009. LINE-1 DNA methylation is inversely correlated with cord plasma homocysteine in man: a preliminary study. Epigenetics, vol. 4(6), 394-398. link>
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2004. Molecular Pathology Shows p16 Methylation in Nonadenomatous Pituitaries from Patients with Cushing's Disease. Clinical Cancer Research, vol. 10(5), 1780-1788. doi>
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2004. Loss of expression of the growth inhibitory gene GADD45γ, in human pituitary adenomas, is associated with CpG island methylation. Oncogene, vol. 23(4), 936-944. doi>
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2004. Pituitary tumour clonality revisited. Front Horm Res.
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2003. Epigenetic change in pituitary tumorigenenis. Endocrine-related cancer, vol. 10(2), 323-330. doi>
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2003. Corticotroph carcinoma presenting as a silent corticotroph adenoma. Pituitary, vol. 6(1), 41-47.
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2003. Genome-wide amplification and allelotyping of sporadic pituitary adenomas identify novel regions of genetic loss. Genes, chromosomes & cancer, vol. 37(3), 225-236. doi>
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2002. Expression of phosphorylated p27 (kip1) protein and Jun activation domain-building protein 1 in human pituitary tumours. Journal of clinical enocrinology and metabolism, vol. 87(8), 2635-2643. doi>
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2002. Expression of G1/S phase checkpoint proteins is frequently abnormal in adrenal cortical tumors. MODERN PATHOLOGY, vol. 15(1), 117A. link>
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2002. Expression of G1/S phase checkpoint proteins is frequently abnormal in adrenal cortical tumors. LABORATORY INVESTIGATION, vol. 82(1), 117A. link>
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2002. Expression of phosphorylated p27 (Kip1) protein and Jun activation domain-binding protein 1 in huma pituitary tumours. Clin Endoocrinol Metab., vol. 87(6), 2635-2643.
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2003. Glutathione S-fransferase GSTP1 genotype are associated with response to androgen ablation therapy advanced prostate cancer. Cancer Detection and Prevention, vol. 26(5), 376-380. doi>
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2002. Loss of ACTH expression in cultured human corticotroph macroadenoma cells consistent with loss of the POMC gene signal sequence. Mol Cell Endocrinol, vol. 189(1-2), 51-57.
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2002. Loss of ACTH expression in cultured human corticotroph macroadenoma cells is consistent with loss of the POMC gene signal sequence. Molecular and Cellular Endocrinology, vol. 189(1-2), 51-57. doi>
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2002. Loss of Heterozygosity on chromosome 10q is associated with earlier onset sporadic colorectal adenocarinoma. International Journal of Cancer, vol. 99(6), 829/833.
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2002. PRKAR1A, one of the Carney complex genes, and its locus (17q22-24) are rarely altered in pituitary tumours outside the Carney complex. Med Genet., vol. 39(12), 78.
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2001. Cyclin D1 \fI(CCNDI)\fP Genotype is Associated with Tumour Grade in Sporadic Pituitary Adenomas. Carcinogenesis. doi>
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2001. Distinct clonal composition of primary and metastatic adrencorticotrophic hormone-producing pituitary carcinoma. Clinical Endocrinology, vol. 55(4), 549-556. doi>
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2001. Clonality of pituitary tumours : More complicated than initially envisaged. Brain Pathology, vol. 11(0), 313/327.
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2001. Clonality of pituitary tumours: More complicated than initially envisaged. Brain Pathology.
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2001. Decreased Proliferation and Cell Cycle Arrest in Neoplastic Rat Pituitary Cells is Associated with Transforming Growth Factor B1 Induced Expression of p15/INK4B. Molecular and Cellular Endocrinology 2001, vol. 76(1/2), 29/37.
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2001. Decreased proliferation and cell cycle arrest in neoplastic rat pituitary cells is associated with transforming growth factor-beta1-induced expression of p15/INK4B. Mol Cell Endocrinol., vol. 176(1-2), 29-37.
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2001. Distinct clonal composition of primary and metastatic adrencorticotphic hormone-producing pituitary carcinoma. Clinical Endocrinology, vol. 55(4), 549/556.
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2001. Distinct clonal composition of primary and metastatic adrencorticotrophic hormone-producing pituitary carcinoma. Clin Endoocrinol (Oxf)., vol. 55(4), 549-556.
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2001. Molecular Aberrations Associated with Pituitary adenomas. Pituitary Disorder in Forum in Neuroscienze 2 (Ed R Buonaguidi (Pages 84-98)).
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2001. Pituitary tumours. Reproduction, 363-371.
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2001. Pituitary tumours. Reproduction, vol. 121(3), 363-371.
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2001. Pituitary tumours show frequent genetic aberrations at the G1/S phase of the cell cycle. Carcinogenesis.
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2001. Pituitary tumours show frequent genetic aberrations at the G1/S phase of the cell cycle. Carcinogenesis, vol. 22(0), 11149/54.
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2000. Different patterns of allelic loss (loss of heterozygosity) in recurrent human pituitary tumors provide evidence for multiclonal origins. Clin Cancer Res, vol. 6(10), 3973-3982. link>
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2000. Region of frequent loss of heterozygosity on long arm of chromosome 10 associated with earlier age of presentation in sporadic colorectal adenocarcinoma. GUT, vol. 46, A53. link>
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2000. Loss of pRb expression in pituitary adenomas is associated with methylation of the RB1 CpG island. Cancer Res, vol. 60(5), 1211-1216. link>
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1999. Analysis of cyclin D1 (CCND1) allelic imbalance and overexpression in sporadic human pituitary tumors. Clin Cancer Res, vol. 5(8), 2133-2139. link>
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1999. Chromosome 13q deletion mapping in pituitary tumors: infrequent loss of the retinoblastoma susceptibility gene (RB1) locus despite loss of RB1 protein product in somatotrophinomas. Cancer Res, vol. 59(7), 1562-1566. link>
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1999. Sporadic colorectal polyps: management options and guidelines. Scand J Gastroenterol, vol. 34(1), 4-11. link>
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1999. Tumour suppressor genes in pituitary tumour formation. Baillieres Best Pract Res Clin Endocrinol Metab., vol. 13(3), 381-393.
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1997. Chromosome 9p deletions in invasive and noninvasive nonfunctional pituitary adenomas: the deleted region involves markers outside of the MTS1 and MTS2 genes. Cancer Res, vol. 57(13), 2703-2709. link>
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1993. Glucocorticoid inhibition of ACTH peptides: small cell lung cancer cell lines are more resistant than pituitary corticotroph adenoma cells. J Mol Endocrinol, vol. 10(1), 25-32. link>
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1989. Pro-opiomelanocortin gene expression and peptide secretion in human small-cell lung cancer cell lines. J Mol Endocrinol, vol. 3(1), 65-70. link>
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Hereditaey non-polyposis colorectal cancer: an updated review. European Journal of Surgical Oncology, vol. 26, 635-645.
Chapters
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2004. ACTH producing adenomas. In World Health Organisation classification of tumours. Pathology and genetics of tumours of endocrine organs. De LA, Lloyd RV, Heitz PU, Eng C (Eds.). IACR Press, Lyon.
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2004. Growth hormone producing adenomas. In World Health Organisation classification of tumours. Pathology and genetics of tumours of endocrine organs. De LA, Lloyd RV, Heitz PU, Eng C (Eds.). IACR Press, Lyon.
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2004. Pituitary tumours, clonality. In Encyclopaedia of Endocrine Diseases. Martini L (Ed.). Elsevier, San Diego.
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2004. Pituitary tumours: introduction. In World Health Organisation classification of tumours. Pathology and genetics of tumours of endocrine organs. De LA, Lloyd RV, Heitz PU, Eng C (Eds.). IACR Press, Lyon.
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2004. Prolactin producing adenomas. In World Health Organisation classification of tumours. Pathology and genetics of tumours of endocrine organs. De LA, Lloyd RV, Heitz PU, Eng C (Eds.). IACR Press, Lyon.
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1996. Putative Tumour Suppressor Gene Deletions in Human Pituitary Tumours. In Pituitary Adenomas: From Basic Research to Diagnosis and Therapy. Werder KV and Fahlbusch R (Eds.). Elsevier.
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1994. Growth of Small Cell Lung Cancer (SCLC) cell lines. In Cell and Tissue Culture: Laboratory Procedures. Griffiths JB, Newell DG, Doyle A (Eds.). John Wiley and Sons Ltd.
Other
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2013. GENOME-WIDE DNA METHYLATION PROFILING IN T CELLS FROM PATIENTS WITH RHEUMATOID ARTHRITIS. RHEUMATOLOGY (vol. 52, p. 143). link>
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2004. Epigenetic mechanisms of tumorigenesis. JOURNAL OF INTERNAL MEDICINE (vol. 255, pp. 697-698). link>
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2001. Metastatic pituitary tumour-Evidence of different clones of origin. American Endocrine Society 2001 83rd Meeting Conference Proceedings.
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2001. Metastic pituitary tumour-Evidence of different clones of origin. American Endo. Society 2001 83rd Meeting Conference Proceedings.
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2001. Stable inheritance of an imposed methylation pattern in the ATt20 cell line is reversed through drug induced demethylation. American Endocrine Society 83rd Meeting Conference abstracts.
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2001. Stable inheritance of an imposed methylation pattern in the ATt20 cell line is reversed through drug induced demethylation. American endocrine Society 83rd Meeting Conference abstracts.
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2001. The role of the tumour suppressor gene p14ARF in pituitary tumorigenesis. American Endo. Society 2001 83rd Meeting conference Proceedings.
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2001. The role of the tumour suppressor gene p14ARF in pituitary tumorigenesis. American Endocrine Society 83rd Meeting conference Proceedings.
The pages of the Fetal Epigenetics Group

