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Research interests

Fig 1 Compartmentalisation of N-terminal HA-tagged hGnRHR and XGnRHR in HeLa cellsOur research interests are in cell signalling and reproductive endocrinology. Most of our work focuses on the hypothalamic decapeptide GnRH, that acts via G-protein coupled receptors on pituitary gonadotrophs to mediate control of reproduction by the CNS. Type I mammalian GnRH receptors are unique in that they lack the C-terminal tails found in other G-protein coupled receptors, and much of our work has addressed the functional relevance of this distinction, placing emphasis on receptor desensitisation and internalisation as well as MAPK activation and receptor compartmentalisation (figure 1).

Most recent work exploits image-based readouts (e.g. fluorescent reporters) for activity of signalling proteins using semi-automated fluorescence microscopy (high content analysis, figure 2). Using this approach we have been exploring the control of GnRH receptor trafficking and the spatial and temporal control of ERK signalling. Since GnRH is secreted in pulses and gonadotrophs and its effects on these cells are dependent upon pulse frequency, we are currently exploring the molecular mechansism by which gonadotrophs decode pulse frequency. This has led to the development of a sophisticated mathematical model for pulsatile GnRH signalling, that we are testing and developing.

Fig 2 Automated HA-GnRHR imaging

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  • IGFBP-1 expression is reduced in human type 2 diabetic glomeruli and modulates β1-integrin/FAK signalling in human podocytes

    Lay, A. C., Hale, L. J., Stowell-Connolly, H., Pope, R. J. P., Nair, V., Ju, W., Marquez, E., Rollason, R., Hurcombe, J. A., Hayes, B., Roberts, T., Gillam, L., Allington, J., Nelson, R. G., Kretzler, M., Holly, J. M. P., Perks, C. M., McArdle, C. A., Welsh, G. I. & Coward, R. J. M., Jul 2021, In: Diabetologia. 64, 7, p. 1690-1702 13 p.

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  • Natriuretic Peptide Expression and Function in GH3 Somatolactotropes and Feline Somatotrope Pituitary Tumours

    Mirczuk, S. M., Scudder, C. J., Read, J. E., Crossley, V. J., Regan, J. T., Richardson, K. M., Simbi, B., McArdle, C. A., Church, D. B., Fenn, J., Kenny, P. J., Volk, H. A., Wheeler-Jones, C. P., Korbonits, M., Niessen, S. J., McGonnell, I. M. & Fowkes, R. C., 22 Jan 2021, In: International Journal of Molecular Sciences. 22, 3, p. 1-17 17 p., 1076.

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  • THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors

    Alexander, S. P., Christopoulos, A., Davenport, A. P., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Davies, J. A., Abbracchio, M. P., Alexander, W., Al-Hosaini, K., Bäck, M., Barnes, N. M., Bathgate, R., Beaulieu, J-M. & 135 others, Bernstein, K. E., Bettler, B., Birdsall, N. J. M., Blaho, V., Boulay, F., Bousquet, C., Bräuner-Osborne, H., Burnstock, G., Caló, G., Castaño, J. P., Catt, K. J., Ceruti, S., Chazot, P., Chiang, N., Chini, B., Chun, J., Cianciulli, A., Civelli, O., Clapp, L. H., Couture, R., Csaba, Z., Dahlgren, C., Dent, G., Singh, K. D., Douglas, S. D., Dournaud, P., Eguchi, S., Escher, E., Filardo, E. J., Fong, T., Fumagalli, M., Gainetdinov, R. R., Gasparo, M. D., Gerard, C., Gershengorn, M., Gobeil, F., Goodfriend, T. L., Goudet, C., Gregory, K. J., Gundlach, A. L., Hamann, J., Hanson, J., Hauger, R. L., Hay, D. L., Heinemann, A., Hollenberg, M. D., Holliday, N. D., Horiuchi, M., Hoyer, D., Hunyady, L., Husain, A., IJzerman, A. P., Inagami, T., Jacobson, K. A., Jensen, R. T., Jockers, R., Jonnalagadda, D., Karnik, S., Kaupmann, K., Kemp, J., Kennedy, C., Kihara, Y., Kitazawa, T., Kozielewicz, P., Kreienkamp, H-J., Kukkonen, J. P., Langenhan, T., Leach, K., Lecca, D., Lee, J. D., Leeman, S. E., Leprince, J., Li, X. X., Williams, T. L., Lolait, S. J., Lupp, A., Macrae, R., Maguire, J., Mazella, J., McArdle, C. A., Melmed, S., Michel, M. C., Miller, L. J., Mitolo, V., Mouillac, B., Müller, C. E., Murphy, P., Nahon, J-L., Ngo, T., Norel, X., Nyimanu, D., O'Carroll, A-M., Offermanns, S., Panaro, M. A., Parmentier, M., Pertwee, R. G., Pin, J-P., Prossnitz, E. R., Quinn, M., Ramachandran, R., Ray, M., Reinscheid, R. K., Rondard, P., Rovati, G. E., Ruzza, C., Sanger, G. J., Schöneberg, T., Schulte, G., Schulz, S., Segaloff, D. L., Serhan, C. N., Stoddart, L. A., Sugimoto, Y., Summers, R., Tan, V. P., Thal, D., Thomas, W. W., Timmermans, P. B. M. W. M., Tirupula, K., Tulipano, G., Unal, H., Unger, T., Valant, C., Vanderheyden, P., Vaudry, D., Vaudry, H., Vilardaga, J-P., Walker, C. S., Wang, J. M., Ward, D. T., Wester, H-J., Willars, G. B., Woodruff, T. M., Yao, C. & Ye, R. D., 16 Sep 2021, In: British Journal of Pharmacology. 178 Suppl 1, S1, p. S27-S156 130 p.

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