Dr Luke Gaughan
- Email: firstname.lastname@example.org
- Telephone: +44 (0) 191 208 4360
- Fax: +44 (0) 191 208 4301
- Address: Northern Institute for Cancer Research
Paul O'Gorman Building
Newcastle upon Tyne
1998: B.SC (Hons) Biochemistry.
2001: Ph.D Molecular Biology
Urology Research Group
School of Surgical and Reproductive Sciences
2001- 2006: Post-Doctoral Research Associate.
Urology Research Group,
Northern Institute For Cancer Research,
Funded by the Association for International Cancer Research (AICR)
British Association for Cancer Research (BACR)
Honours and Awards
British Association for Cancer Research Young Translational Scientist Award 2006
1. Mechanisms of Androgen Receptor (AR) Regulation in Prostate Cancer
2. Epigenetics and Transcription of AR and Estrogen Receptor (ER)
Histone methyltransferases (HMTs), histone acetyltranferases (HATs) and the enzymes that reverse the effects of these proteins play a fundamental role in regulating transcription. My group are currently deciphering the roles of several HMT and histone demethylase enzymes in AR and ER regulation in prostate and breast cancer development. We are particularly interested in the global epigenetic changes that occur as a means of facilitating nuclear hormone receptor transcriptional activity and how they are deregulated in transformed cells.
Outside of this area, the group is currently generating novel tools to assess structure-function relationships of specific domains of the AR to potentiate the development of new receptor-targeting therapeutics for prostate cancer. This is being performed in conjunction with Astex Pharmaceuticals as part of an MRC CASE studentship.
As part of a Cancer Research UK and AstraZeneca co-funded PhD studentship project we have developed a highly informative cell-based system to characterise prostate cancer-relevant AR mutations for testing of new therapeutics against aberrantly functioning receptors, and to provide biomarkers for disease stratification and, ultimately, novel targets for therapy.
2012-2016: MRC-funded PhD student
2014-2018: Cancer Research UK-funded PhD student
2015-2019: Prostate Cancer UK-funded PhD student
Cancer Research UK: Funding one PhD student (2014-2018)
Medical Research Council and Astex Pharmaceuticals: Funding one PhD student (2012-2016)
Prostate Cancer UK: Funding one PhD student (2015-2019)
Worldwide Cancer Research: Funding one post-doctoral research associate (2011-2015)
Teaching2008-Present: BMS3007 Research in Biomedical Sciences, Lecturer
2009-Present: BMS3012 Cancer Biology and Therapy, Lecturer
2010-Present:BMS 3008 Integrated Biomedical Sciences, Module Leader
- Grey J, Jones D, Wilson L, Nakjang S, Clayton J, Temperley R, Clark E, Gaughan L, Robson C. Differential regulation of the androgen receptor by protein phosphatase regulatory subunits. Oncotarget 2018, 9(3), 3922-3935.
- Shuttleworth VG, Gaughan L, Nawafa L, Mooney CA, Cobb SL, Sheerin NS, Logan IR. The methyltransferase SET9 regulates TGFB1 activation of renal fibroblasts via interaction with SMAD3. Journal of Cell Science 2018, 131, jcs207761.
- Jones D, Noble M, Wedge SR, Robson CN, Gaughan L. Aurora A regulates expression of AR-V7 in models of castrate resistant prostate cancer. Scientific Reports 2017, 7, 40957.
- McClurg UL, Cork DMW, Darby S, Ryan-Munden CA, Nakjang S, Mendes-Cortes L, Treumann A, Gaughan L, Robson CN. Identification of a novel K311 ubiquitination site critical for androgen receptor transcriptional activity. Nucleis Acids Research 2017, 45(4), 1793-1804.
- Logan IR, McClurg UL, Jones DL, O'Neill DJ, Shaheen FS, Lunec J, Gaughan L, Robson CN. Nutlin-3 inhibits androgen receptor-driven c-FLIP expression, resulting in apoptosis of prostate cancer cells. Oncotarget 2016, 7(46), 74724-74733.
- Rodriguez-Teja M, Gronau JH, Breit C, Zhang YZ, Minamidate A, Caley MP, McCarthy A, Cox TR, Erler JT, Gaughan L, Darby S, Robson C, Mauri F, Waxman J, Sturge J. AGE-modified basement membrane cooperates with Endo180 to promote epithelial cell invasiveness and decrease prostate cancer survival. Journal of Pathology 2015, 235(4), 581-592.
- O'Neill D, Jones D, Wade M, Grey J, Nakjang S, Guo W, Cork D, Davies BR, Wedge SR, Robson CN, Gaughan L. Development and exploitation of a novel mutant androgen receptor modelling strategy to identify new targets for advanced prostate cancer therapy. Oncotarget 2015, 6(28), 26029-26040.
- Jones D, Wade M, Nakjang S, Chaytor L, Grey J, Robson CN, Gaughan L. FOXA1 regulates androgen receptor variant activity in models of castrate-resistant prostate cancer. Oncotarget 2015, 6(30), 29782-29794.
- Cano LQ, Lavery DN, Sin S, Spanjaard E, Brooke GN, Tilman JD, Abroaf A, Gaughan L, Robson CN, Heer R, Mauri F, de Rooij J, Driouch K, Bevan CL. The co-chaperone p23 promotes prostate cancer motility and metastasis. Molecular Oncology 2015, 9(1), 295-308.
- Wade MA, Jones D, Wilson L, Stockley J, Coffey K, Robson CN, Gaughan L. The histone demethylase enzyme KDM3A is a key estrogen receptor regulator in breast cancer. Nucleic Acids Research 2015, 43(1), 196-207.
- Logan IR, Shuttleworth VG, Gaughan L, Nawafa LS, Sheerin NS. The Lysine Methyltransferase SETD7 is critical for TGF B-1 driven fibrosis. In: 52nd ERA-EDTA Congress. 2015, London, UK: Oxford University Press.
- McClurg UL, Harle VJ, Nabbi A, Batalha-Pereira A, Walker S, Coffey K, Gaughan L, McCracken SRC, Robson CN. Ubiquitin-specific protease 12 interacting partners Uaf-1 and WDR20 are potential therapeutic targets in prostate cancer. Oncotarget 2015, 6(35).
- McClurg UL, Summerscales EE, Harle VJ, Gaughan L, Robson CN. Deubiquitinating enzyme Usp12 regulates the interaction between the androgen receptor and the Akt pathway. Oncotarget 2014, 5(16), 7081-7092.
- O'Neill DJ, Williamson SC, Alkharaif D, Monteiro ICM, Goudreault M, Gaughan L, Robson CN, Gingras AC, Binda O. SETD6 controls the expression of estrogen-responsive genes and proliferation of breast carcinoma cells. Epigenetics 2014, 9(7), 942-950.
- Rodriguez-Teja M, Gronau JH, Minamidate A, Darby S, Gaughan L, Robson C, Mauri F, Waxman J, Sturge J. Survival Outcome and EMT Suppression Mediated by a Lectin Domain Interaction of Endo180 and CD147. Molecular Cancer Research 2014.
- Loddick SA, Ross SJ, Thomason AG, Robinson DM, Walker GE, Dunkley TPJ, Brave SR, Broadbent N, Stratton NC, Trueman D, Mouchet E, Shaheen FS, Jacobs VN, Cumberbatch M, Wilson J, Jones RDO, Bradbury RH, Rabow A, Gaughan L, Womack C, Barry ST, Robson CN, Critchlow SE, Wedge SR, Brooks AN. AZD3514: A Small Molecule That Modulates Androgen Receptor Signaling and Function In Vitro and In Vivo. Molecular Cancer Therapeutics 2013, 12(9), 1715-1727.
- Burska UL, Harle VJ, Coffey K, Darby S, Ramsey H, O'Neill D, Logan IR, Gaughan L, Robson CN. Deubiquitinating Enzyme Usp12 Is a Novel Co-activator of the Androgen Receptor. Journal of Biological Chemistry 2013, 288(45), 32641-32650.
- Gaughan L, Stockley J, Coffey K, O'Neill D, Jones DL, Wade M, Wright J, Moore M, Tse S, Rogerson L, Robson CN. KDM4B is a Master Regulator of the Estrogen Receptor Signalling Cascade. Nucleic Acids Research 2013, 41(14), 6892-6904.
- Coffey K, Rogerson L, Ryan-Munden C, Alkharaif D, Stockley J, Heer R, Sahadevan K, O'Neill D, Jones D, Darby S, Staller P, Mantilla A, Gaughan L, Robson CN. The lysine demethylase, KDM4B, is a key molecule in androgen receptor signalling and turnover. Nucleic Acids Research 2013, 41(8), 4433-4446.
- Axon A, May FEB, Gaughan LE, Williams FM, Blain PG, Wright MC. Tartrazine and sunset yellow are xenoestrogens in a new screening assay to identify modulators of human oestrogen receptor transcriptional activity. Toxicology 2012, 298(1-3), 40-51.
- Brooke GN, Culley RL, Dart DA, Mann DJ, Gaughan L, McCracken SR, Robson CN, Spencer-Dene B, Gamble SC, Powell SM, Wait R, Waxman J, Walker MM, Bevan CL. FUS/TLS Is a Novel Mediator of Androgen-Dependent Cell-Cycle Progression and Prostate Cancer Growth. Cancer Research 2011, 71(3), 914-924.
- Rajan P, Dalgliesh C, Carling PJ, Buist T, Zhang CL, Grellscheid SN, Armstrong K, Stockley J, Simillion C, Gaughan L, Kalna G, Zhang MQ, Robson CN, Leung HY, Elliott DJ. Identification of Novel Androgen-Regulated Pathways and mRNA Isoforms through Genome-Wide Exon-Specific Profiling of the LNCaP Transcriptome. PLoS One 2011, 6(12), e29088.
- Gaughan L, Stockley J, Wang N, McCracken S, Truemann A, Armstrong K, Shaheen F, Watt K, McEwan I, Wang C, Pestell RG, Robson CN. Regulation of the androgen receptor by SET9-mediated methylation. Nucleic Acids Research 2011, 39(4), 1266-1279.
- Shaheen FS, Znojek P, Fisher A, Webster M, Plummer R, Gaughan L, Smith GCM, Leung HY, Curtin NJ, Robson CN. Targeting the DNA Double Strand Break Repair Machinery in Prostate Cancer. PLoS One 2011, 6(5), e20311.
- Rajan P, Gaughan L, Dalgliesh C, El-Sherif A, Robson CN, Leung HY, Elliott DJ. Regulation of gene expression by the RNA-binding protein Sam68 in cancer. Biochemical Society Transactions 2008, 36(3), 505-507.
- Clark EL, Coulson AC, Dalgliesh C, Rajan P, Nicol SM, Fleming S, Heer R, Gaughan L, Leung HY, Elliott DJ, Fuller-Pace FV, Robson CN. The RNA helicase p68 is a novel androgen receptor coactivator involved in splicing and is overexpressed in prostate cancer. Cancer Research 2008, 68(19), 7938-7946.
- Rajan P, Gaughan L, Dalgliesh C, El-Sherif A, Robson CN, Leung HY, Elliott DJ. The RNA-binding and adaptor protein Sam68 modulates signal-dependent splicing and transcriptional activity of the androgen receptor. Journal of Pathology 2008, 215(1), 67-77.
- Logan IR, Gaughan L, McCracken SRC, Sapountzi V, Leung HY, Robson CN. Human PIRH2 enhances androgen receptor signaling through inhibition of histone deacetylase 1 and is overexpressed in prostate cancer. Molecular and Cellular Biology 2006, 26(17), 6502-6510.
- Awasthi, S, Sharma, A, Wong, K, Zhang, J, Matlock, E, Rogers, L, Motloch, P, Takemoto, S, Taguchi, H, Cole, MD, Lüscher, B, Dittrich, O, Tagami, H, Nakatani, Y, McGee, M, Girard, AM, Gaughan, L, Robson, CN, Monnat, RJ, Harrod, R. A human T-cell lymphotropic virus type 1 enhancer of Myc transforming potential stabilizes Myc-TIP60 transcriptional interactions. Molecular and Cellular Biology 2005, 25(14), 6178-6198.
- Mills, I., Gaughan, L., Robson, C. N., Ross, T., McCracken, S. R. C., Kelly, J., Neal, D. E. Huntingtin interacting protein 1 modulates the transcriptional activity of nuclear hormone receptors. Journal of Cell Biology 2005, 170(2), 191-200.
- Gaughan, L., Logan, I. R., Neal, D. E., Robson, C. N. Regulation of androgen receptor and histone deacetylase 1 by Mdm2-mediated ubiquitylation. Nucleic Acids Research 2005, 33(1), 13-26.
- Logan, I. R., Sapountzi, V., Gaughan, L., Neal, D. E., Robson, C. N. Control of human PIRH2 protein stability: Involvement of TIP60 and the proteasome. Journal of Biological Chemistry 2004, 279(12), 11696-11704.
- Halkidou, K., Gaughan, L., Cook, S., Leung, H. Y., Neal, D. E., Robson, C. N. Upregulation and nuclear recruitment of HDACI in hormone refractory prostate cancer. The Prostate 2004, 59(2), 177-189.
- Gaughan, L., Neal, D. E., Robson, C. N. The role of Mdm2 in androgen receptor regulation. European Urology Supplements 2003, 2(6), 58-58.
- Gaughan, L., Logan, I. R., Cook, S., Neal, D. E., Robson, C. N. Tip60 and histone deacetylase 1 regulate androgen receptor activity through changes to the acetylation status of the receptor. Journal of Biological Chemistry 2002, 277(29), 25904-25913.
- Gaughan, L., Brady, M. E., Cook, S., Neal, D. E., Robson, C. N. Tip60 is a co-activator specific for class I nuclear hormone receptors. Journal of Biological Chemistry 2001, 276(50), 46841-46848.
- Ozanne, D. M., Brady, M. E., Cook, S., Gaughan, L., Neal, D. E., Robson, C. N. Androgen receptor nuclear translocation is facilitated by the f-actin cross-linking protein filamin. Molecular Endocrinology 2000, 14(10), 1618-1626.
- Brady, M. E., Ozanne, D. M., Gaughan, L., Waite, I. S., Cook, S., Neal, D. E., Robson, C. N. Tip60 is a nuclear hormone receptor coactivator. Journal of Biological Chemistry 1999, 274(25), 17599-17604.