4 South 0.64
Tel: +44 (0) 1225 386914
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Current lab members
- Xiao Hu
- Kim Moorwood
- Sasi Saminathan
Prof Andrew Ward
My main interests are to understand:
(i) how fetal growth is regulated such that a body of correct size and proportions is attained
(ii) how altered fetal growth can influence health in later life, including predisposition to cancer, obesity and diabetes.
These are big questions, relevant to important medical problems. Our approach has been to focus on a small group of genes regulated by genomic imprinting. Imprinted genes behave unusually in that they are expressed predominantly, if not exclusively, from only one of their two parental copies. Although only about 100 imprinted genes are known, a large proportion of them regulate fetal growth and/or adult physiology, with others influencing brain function and behaviour.
The Grb10 gene is expressed from the maternally-inherited copy in most fetal tissues outside of the central nervous system and we have shown that it acts to inhibit growth of both the embryo and placenta. In adult life the maternally-inherited Grb10 allele regulates insulin receptor signalling and body fat deposition and can, therefore, directly influence energy homeostasis. Recently, we found that in the brain Grb10 is expressed mainly from the paternal allele and we have discovered that this brain expression is linked with the control of social dominance behaviour. By gaining a deeper understanding of the different functions of Grb10 we aim to understand why this and other imprinted genes have evolved.
Ferrón, S. R., Radford, E. J., Domingo-Muelas, A., Kleine, I., Ramme, A., Gray, D., Sandovici, I., Constancia, M., Ward, A., Menheniott, T. R. and Ferguson-Smith, A. C., 2015. Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis. Nature Communications, 6, 8265.
Williams, J. M., Ball, M., Ward, A. and Moore, T., 2015. Psg22 expression in mouse trophoblast giant cells is associated with gene inversion and co-expression of antisense long non-coding RNAs. Human Reproduction, 149, pp. 125-137.
Madon-Simon, M., Cowley, M., Garfield, A. S., Moorwood, K. and Ward, A., 2014. Antagonistic roles in fetal development and adult physiology for the oppositely imprinted Grb10 and Dlk1 genes. BMC Biology, 12, 771.
Nordin, M., Bergman, D., Halje, M., Engström, W. and Ward, A., 2014. Epigenetic regulation of the Igf2/H19 gene cluster. Cell Proliferation, 47 (3), pp. 189-199.
Cowley, M., Garfield, A. S., Madon-Simon, M., Charalambous, M., Clarkson, R. W., Smalley, M. J., Kendrick, H., Isles, A. R., Parry, A. J., Carney, S., Oakey, R. J., Heisler, L. K., Moorwood, K., Wolf, J. B. and Ward, A., 2014. Developmental Programming Mediated by Complementary Roles of Imprinted Grb10 in Mother and Pup. PLoS Biology, 12 (2), e1001799.
Garfield, A. S., Cowley, M., Smith, F. M., Moorwood, K., Stewart-Cox, J. E., Gilroy, K., Baker, S., Xia, J., Dalley, J. W., Hurst, L. D., Wilkinson, L. S., Isles, A. R. and Ward, A., 2011. Distinct physiological and behavioural functions for parental alleles of imprinted Grb10. Nature, 469 (7331), pp. 534-538.
Recino, A., Sherwood, V., Flaxman, A., Cooper, W. N., Latif, F., Ward, A. and Chalmers, A. D., 2010. Human RASSF7 regulates the microtubule cytoskeleton and is required for spindle formation, Aurora B activation and chromosomal congression during mitosis. Biochemical Journal, 430 (2), pp. 207-213.
Charalambous, M., Cowley, M., Geoghegan, F., Smith, F. M., Radford, E. J., Marlow, B. P., Graham, C. F., Hurst, L. D. and Ward, A., 2010. Maternally-inherited Grb10 reduces placental size and efficiency. Developmental Biology, 337 (1), pp. 1-8.
Ward, A. and Tosh, D., eds., 2010. Mouse Cell Culture: Methods and Protocols.Vol. 633. Humana Press.
Sherwood, V., Recino, A., Jeffries, A., Ward, A. and Chalmers, A. D., 2010. The N-terminal RASSF family: a new group of Ras-association-domain-containing proteins, with emerging links to cancer formation. Biochemical Journal, 425 (2), pp. 303-311.
Lock, F. E., Underhill-Day, N., Dunwell, T., Matallanas, D., Cooper, W., Hesson, L., Recino, A., Ward, A., Pavlova, T., Zabarovsky, E., Grant, M. M., Maher, E. R., Chalmers, A. D., Kolch, W. and Latif, F., 2010. The RASSF8 candidate tumor suppressor inhibits cell growth and regulates the Wnt and NF-κB signaling pathways. Oncogene, 29 (30), pp. 4307-4316.
Dallosso, A. R., Hancock, A. L., Szemes, M., Moorwood, K., Chilukamarri, L., Tsai, H. H., Sarkar, A., Barasch, J., Vuononvirta, R., Jones, C., Pritchard-Jones, K., Royer-Pokora, B., Lee, S. B., Owen, C., Malik, S., Feng, Y., Frank, M., Ward, A., Brown, K. W. and Malik, K., 2009. Frequent long-range epigenetic silencing of Protocadherin gene clusters on chromosome 5q31 in Wilms' Tumor. Plos Genetics, 5 (11), e1000745.
Pink, C. J., Swaminathan, S. K., Dunham, I., Rogers, J., Ward, A. and Hurst, L. D., 2009. Evidence that replication-associated mutation alone does not explain between-chromosome differences in substitution rates. Genome Biology and Evolution, 2009, pp. 13-22.
Holt, L. J., Lyons, R. J., Ryan, A. S., Beale, S. M., Ward, A., Cooney, G. J. and Daly, R. J., 2009. Dual ablation of Grb10 and Grb14 in mice reveals their combined role in regulation of insulin signaling and glucose homeostasis. Molecular Endocrinology, 23 (9), pp. 1406-1414.
Lopes, S. S., Yang, X. Y., Muller, J., Carney, T. J., McAdow, A. R., Rauch, G.-J., Jacoby, A. S., Hurst, L. D., Delfino-Machin, M., Haffter, P., Geisler, R., Johnson, S. L., Ward, A. and Kelsh, R. N., 2008. Leukocyte tyrosine kinase functions in pigment cell development. Plos Genetics, 4 (3), e1000026.
Dutton, J. R., Antonellis, A., Carney, T. J., Rodriguez, F. S. L. M., Pavan, W. J., Ward, A. and Kelsh, R. N., 2008. An evolutionarily conserved intronic region controls the spatiotemporal expression of the transcription factor Sox10. BMC Developmental Biology, 8 (1), p. 105.