Brooke, Greg - University of Essex - School of Biological Sciences

个人简介

Jul 2000 Research Associate, Department of Cancer Biology, Imperial College London Oct 2001 PhD, Department of Cancer Biology, Imperial College London Oct 2005 Post-Doctoral Research Fellow, Department of Surgery and Cancer, Imperial College London Oct 2010 Senior Research Fellow, Martin Harris Fellowship, Department of Surgery and Cancer, Imperial College London Jul 2013 Lecturer, School of Biological Sciences, University of Essex

研究领域

Key Research Aim Identify and characterise factors that promote tumour growth and therapy resistance in prostate and breast cancer. Research Summary Prostate and breast cancer are leading causes of cancer-related death in men and women respectively. The growth of prostate cancer is dependent upon the male sex hormone androgen, whereas the growth of breast cancer is usually dependent upon the female sex hormone oestrogen. For this reason, a common therapeutic strategy for the treatment of these diseases is hormone therapy, which aims to block the production and/or action of these hormones. Hormone therapy is initially successful in the majority of patients, but relapse is a common problem and the tumours progress to the castrate or endocrine resistant stage of the disease. Chemotherapy is an option for hormone therapy resistant disease, but resistance is also commonly associated with these agents. My research aims to identify and characterise factors that drive tumour growth and factors that promote therapy resistance. It is hoped that this research will identify much-needed novel therapeutic targets for these diseases and to identify biomarkers that will predict whether a patient will respond to a therapeutic. The latter will allow patients and clinicians to make more informed decisions regarding therapeutic options and promote personalised medicine. An example of this research was the identification of FUS, a multi-functional RNA binding protein, as a key mediator of prostate cancer growth. Through analysis of patient samples, we identified that FUS levels were significantly lower in aggressive stages of the disease and that FUS expression inversely correlated with survival. Modulation of FUS levels in cancer cells demonstrated that FUS is a potent inhibitor of tumour growth and that it promotes cell death. Detailed analysis demonstrated that FUS directly regulates factors important in cell cycle progression (e.g. Cyclin D1) thus linking androgen signalling and cell cycle regulation. We are currently further investigating if FUS could be used as a biomarker to predict disease aggressiveness and investigating methods to increase FUS expression in tumours, which we believe will block tumour growth.

近期论文

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Brooke, G. N., Gamble, S. C., Hough, M. A., Begum, S., Dart, D. A., Odontiadis, M., Powell, S. M., Fioretti, F. M., Bryan, R. A., Waxman, J., Wait, R. & Bevan, C. L. Antiandrogens Act as Selective Androgen Receptor Modulators at the Proteome Level in Prostate Cancer Cells. Molecular & Cellular Proteomics 14, 1201-1216, (2015). Cano, L. Q., Lavery, D. N., Sin, S., Spanjaard, E., Brooke, G. N., Tilman, J. D., Abroaf, A., Gaughan, L., Robson, C. N., Heer, R., Mauri, F., de Rooij, J., Driouch, K. & Bevan, C. L. The co-chaperone p23 promotes prostate cancer motility and metastasis. Mol Oncol 9, 295-308, (2015). Rudraraju, B., Droog, M., Abdel-Fatah, T. M., Zwart, W., Giannoudis, A., Malki, M. I., Moore, D., Patel, H., Shaw, J., Ellis, I. O., Chan, S., Brooke, G. N., Nevedomskaya, E., Lo Nigro, C., Carroll, J., Coombes, R. C., Bevan, C., Ali, S. & Palmieri, C. Phosphorylation of activating transcription factor-2 (ATF-2) within the activation domain is a key determinant of sensitivity to tamoxifen in breast cancer. Breast cancer research and treatment 147, 295-309, (2014). Fioretti, F. M., Sita-Lumsden, A., Bevan, C. L. & Brooke, G. N. Revising the role of the androgen receptor in breast cancer. Journal of molecular endocrinology 52, R257-265, (2014). Brooke, G. N., Powell, S. M., Lavery, D. N., Waxman, J., Buluwela, L., Ali, S. & Bevan, C. L. Engineered repressors are potent inhibitors of androgen receptor activity. Oncotarget 5, 959-969, (2014). Sita-Lumsden, A., Fletcher, C. E., Dart, D. A., Brooke, G. N., Waxman, J. & Bevan, C. L. Circulating nucleic acids as biomarkers of prostate cancer. Biomark Med 7, 867-877, (2013). Ottaviani, S., Brooke, G. N., O'Hanlon-Brown, C., Waxman, J., Ali, S. & Buluwela, L. Characterisation of the androgen regulation of glycine N-methyltransferase in prostate cancer cells. Journal of molecular endocrinology 51, 301-312, (2013). Brooke, G. N., Waxman, J. Bevan, C. L. The Role of Androgen Receptor Mutations in Progression of Prostate Cancer in Advances in Genome Science, Changing Views on Living Organisms Vol. 1 (ed C. Neri) 45-65 (Bentham Science Publishers, 2013). Reebye, V., Cano, L. Q., Lavery, D. N., Brooke, G. N., Powell, S. M., Chotai, D., Walker, M. M., Whitaker, H. C., Wait, R., Hurst, H. C. & Bevan, C. L. Role of the HSP90-Associated Cochaperone p23 in Enhancing Activity of the Androgen Receptor and Significance for Prostate Cancer. Molecular endocrinology 26, 1694-1706, (2012). Grosdidier, S., Carbo, L. R., Buzon, V., Brooke, G. N., Nguyen, P., Baxter, J. D., Bevan, C. L., Webb, P., Estebanez-Perpina, E. & Fernandez-Recio, J. Allosteric Conversation in the Androgen Receptor Ligand-Binding Domain Surfaces. Molecular endocrinology 26, 1078-1090, (2012). Dart, D. A., Brooke, G. N., Sita-Lumsden, A., Waxman, J. & Bevan, C. L. Reducing prohibitin increases histone acetylation, and promotes androgen independence in prostate tumours by increasing androgen receptor activation by adrenal androgens. Oncogene 31, 4588-4598, (2012). Brooke, G. N., Culley, R. L., Dart, D. A., Mann, D. J., Gaughan, L., McCracken, S. R., Robson, C. N., Spencer-Dene, B., Gamble, S. C., Powell, S. M., Wait, R., Waxman, J., Walker, M. M. & Bevan, C. L. FUS/TLS is a novel mediator of androgen-dependent cell-cycle progression and prostate cancer growth. Cancer research 71, 914-924, (2011). Brooke, G. N. & Bevan, C. L. The role of androgen receptor mutations in prostate cancer progression. Curr Genomics 10, 18-25, (2009). Brooke, G. N., Parker, M. G. & Bevan, C. L. Mechanisms of androgen receptor activation in advanced prostate cancer: differential co-activator recruitment and gene expression. Oncogene 27, 2941-2950, (2008). Gamble, S. C., Chotai, D., Odontiadis, M., Dart, D. A., Brooke, G. N., Powell, S. M., Reebye, V., Varela-Carver, A., Kawano, Y., Waxman, J. & Bevan, C. L. Prohibitin, a protein downregulated by androgens, represses androgen receptor activity. Oncogene 26, 1757-1768, (2007). Powell, S. M., Brooke, G. N., Whitaker, H. C., Reebye, V., Gamble, S. C., Chotai, D., Dart, D. A., Belandia, B. & Bevan, C. L. Mechanisms of androgen receptor repression in prostate cancer. Biochem Soc T 34, 1124-1127, (2006). Brooke, G. N., Bevan, C. L. The androgen receptor and its role in progression of prostate cancer from androgen dependence to androgen independence. IBScientific Journal of Science 1, 52-63, (2006). Vigushin, D. M., Mirsaidi, N., Brooke, G. N., Sun, C., Pace, P., Inman, L., Moody, C. J. & Coombes, R. C. Gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with antitumor activity against breast cancer in vivo. Med Oncol 21, 21-30, (2004). Vigushin, D. M., Brooke, G., Willows, D., Coombes, R. C. & Moody, C. J. Pyrazino[1,2-a]indole-1,4-diones, simple analogues of gliotoxin, as selective inhibitors of geranylgeranyltransferase I. Bioorg Med Chem Lett 13, 3661-3663, (2003). Marson, C. M., Rioja, A. S., Brooke, G. N., Coombes, R. C. & Vigushin, D. M. Cyclic acid anhydrides as a new class of potent, selective and non-peptidic inhibitors of geranylgeranyl transferase. Bioorg Med Chem Lett 12, 255-259, (2002).