Wendy’s previous research has focussed on control of gene expression via epigenetic mechanisms; this has included work on the RASSF family of tumour suppressor genes that are frequently inactivated in tumours via DNA methylation, and on the imprinted H19/IGF2 locus where epigenetic dysregulation can cause birth defects and tumour predisposition (Beckwith Wiedemann Syndrome). This work was carried out in the laboratories of Professors Eamonn Maher and Farida Latif at the University of Birmingham Department of Medical and Molecular Genetics and was funded by Breast Cancer Campaign and by Sport Aiding Medical Research for Kids
Wendy has also worked on the epigenetic control of gene expression in non-cancer fields, this work, at The University of Cambridge Department of Obstetrics and Gynaecology and Institute of Metabolic Science focussed on fetal growth and the developmental programming of health and disease. There is accumulating evidence that later life outcomes may be programmed in utero such that a malevolent foetal environment may predispose to a subsequent increased risk of obesity, type 2 diabetes and cardiovascular disease. Epigenetic mechanisms offer dynamic, heritable and reversible mechanisms of modulating genome function that may be able to respond to environmental cues modulating phenotype. Malevolent fetal environments include genetically modulated growth restriction and suboptimal nutritional environments. An important genetic regulator of fetal growth is IGF2 which harbours a co-expressed microRNA, miR-483. In work funded by MRC, we performed experiments to determine the function of miR-483 and to understand the separate roles of Igf2 and miR-483. Suboptimal nutrient supply during early embryonic development could program alternative methylation patterns that preserve fetal viability at the expense of increased morbidity in adult life. In work funded by BBSRC, we compared the methylation in the blood at a genome wide level and at specific loci between children whose mothers diets were or were not supplemented with micronutrients during the periconceptional period.
Quilter, C.R., Cooper, W.N., Cliffe, K.M., Skinner, B.M., Prentice, P.M., Nelson, L., Bauer, J., Ong, K.K., Constância, M., Lowe, W.L., Affara, N.A., Dunger, D.B. (2014) Impact on offspring methylation patterns of maternal gestational diabetes mellitus and intrauterine growth restraint suggest common genes and pathways linked to subsequent type 2 diabetes risk. FASEB J. 28 4868-79.
Khulan, B., Cooper, W.N., Skinner, B., Bauer, J., Owens, S., Prentice, A.M., Belteki, G., Constancia, M., Dunger, D., and Affara, N.A. (2012) Periconceptional maternal micronutrient supplementation leads to widespread changes in the epigenome: a study of a unique resource in the Gambia. Hum Mol Genet. 21 2086-2101.
Astuti, D., Morris, M.R., Cooper, W.N., Staals, R.H., Wake, N.C., Fews, G.A., Gill, H., Gentle, D., Shuib, S., Ricketts, C.J., Cole, T., van Essen, A.J., van Lingen, R.A., Neri, G., Opitz, J.M., Rump, P., Stolte-Dijkstra, I., Müller, F., Pruijn, G.J., Latif, F., and Maher, E.R. (2012) Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility. Nat Genet. 44 277-284.
Cooper, W.N., Khulan, B., Owens, S., Elks, C.E., Seidel, V., Prentice, A.M., Belteki, G., Ong, K.K., Affara, N.A., Constância, M., and Dunger, D.B. (2012). DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans: results of a pilot randomized controlled trial. FASEB J. 26 1782-1790.
Cooper, W.N., Hesson, L.B., Matallanas, D., Dallol, A., von Kriegsheim, A., Ward, R., Kolch, W., and Latif, F. (2009). RASSF2 associates with and stabilizes the proapoptotic kinase MST2. Oncogene 28 2988-2998.
Cooper, W.N., Dickinson, R.E., Dallol, A., Grigorieva, E.V., Pavlova, T.V., Hesson, L.B., Bieche, I., Broggini, M., Maher, E.R., Zabarovsky, E.R., Clark, G.J. and Latif, F. (2008). Epigenetic regulation of the ras effector/tumour suppressor RASSF2 in breast and lung cancer. Oncogene 27 1805-11.
Cooper, W.N., Curley, R., Macdonald, F. and Maher, E.R. (2007). Mitotic recombination and uniparental disomy in Beckwith-Wiedemann syndrome. Genomics 89 613-617.
Dallol, A., Cooper, W.N., Al-Mulla, F., Agathanggelou, A., Maher, E.R. and Latif, F. (2007). Depletion of the Ras association domain family 1, isoform A-associated novel microtubule-associated protein, C19ORF5/MAP1S, causes mitotic abnormalities. Cancer Research 67 492-500.
Cooper, W.N., Luharia, A., Evans, G.A., Raza, H., Haire, A.C., Grundy, R., Bowdin, S.C., Riccio, A., Sebastio, G., Bliek, J., Schofield, P.N., Reik, W., Macdonald, F. and Maher, E.R. (2005). Molecular subtypes and phenotypic expression of Beckwith-Wiedemann syndrome. European Journal of Human Genetics 13 1025-1032.
Maher, E.R., Brueton, L.A., Bowdin, S.C., Luharia, A., Cooper, W., Cole, T.R., Macdonald, F., Sampson, J.R., Barratt, C.L., Reik, W. and Hawkins, M.M. (2003). Beckwith-Wiedemann syndrome and assisted reproduction technology (ART). Journal of Medical Genetics 40, 62-64.