Staff Profile

Qualifications

1998: B.SC (Hons) Biochemistry.
Newcastle University

2001: Ph.D Molecular Biology
Urology Research Group
School of Surgical and Reproductive Sciences
Newcastle University

Previous Positions

2001- 2006: Post-Doctoral Research Associate.
Urology Research Group,
Northern Institute For Cancer Research,
Newcastle University.
Funded by the Association for International Cancer Research (AICR)

Memberships

British Association for Cancer Research (BACR)

Endocrine Society

Honours and Awards

British Association for Cancer Research Young Translational Scientist Award 2006

 

Research Interests

1. Mechanisms of Androgen Receptor (AR) Regulation in Prostate Cancer
2. Epigenetics and splicing control of AR synthesis 

Current Work

The main theme of my research over the last 5 years has been to examine key molecular processes that govern and facilitate AR signalling in advanced prostate cancer with the ultimate objective to identify new targets for therapy. By developing new models of hormone

therapy-resistance that includes engineered cell lines (O’Neill et al., 2015; Jones et al., 2015; Jones et al., 2017) and patient biopsy material as explants, our toolkit for prostate cancer research has evolved to enable more robust, clinically-relevant interrogation of AR function. This has resulted in productive and long-standing industrial collaborations with AstraZeneca, and more recently with CellCentric and J&J, to facilitate Newcastle-based mechanism of action and efficacy studies of several clinical candidate epigenetic and hormonal therapeutics.

 

In the last 5 years, the group has identified and comprehensively validated a number of key AR coregulators in PC development, such as the histone demethylase enzyme KDM4B, which entered a collaborative CR UK-funded drug development campaign in collaboration with the Institute of Cancer Research, Sutton. In addition, our work has identified key processes that govern generation and activity of alternatively spliced forms of the AR, including Aurora kinase A and FOXA1. Furthermore, we have provided insight into the altered functionality of AR mutants in advanced disease that has highlighted new treatment targets and biomarkers for patients resistant to the hormonal therapies bicalutamide and enzalutamide.

 

Our more recent work has focused on the use of genome editing techniques to create genetically altered cell lines (e.g. CWR22Rv1-AR-EK; Kounatidou et al., (2019) Nucleic Acids Research) and as a platform to enable locus specific fluorescence and protein-protein interaction studies of all AR isoforms.

Postgraduate Supervision

2017-2021: Cancer Research UK-funded PhD student

2018-2022: Cancer Research UK-funded PhD student

2019-2023: BBSRC CASE studentship with AstraZeneca

2019-2023: Cancer Research UK-funded PhD student

2020-2024: Prostate Cancer Research-funded PhD student

 

Funding

Medical Research Council Industry Collaboration Award (AstraZeneca) (2017-2020)

Prostate Cancer Foundation Challenge Award (2019-2021)

Prostate Cancer Research (2019-2023)

Cancer Research UK

 

 

 

 

2008-Present: BMS3007 Research in Biomedical Sciences, Lecturer


2009-Present: BMS3012 Cancer Biology and Therapy, Lecturer


2010-Present:BMS 3008 Integrated Biomedical Sciences, Module Leader

• Articles

  • Garnham R, Geh D, Nelson R, Ramon-Gil E, Wilson L, Schmidt EN, Walker L, Adamson B, Buskin A, Hepburn AC, Hodgson K, Kendall H, Frame FM, Maitland N, Coffey K, Strand DW, Robson CN, Elliott DJ, Heer R, Macauley M, Munkley J, Gaughan L, Leslie J, Scott E. ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3Gal1) synthesis of Siglec ligands mediates anti-tumour immunity in prostate cancer. Communications Biology 2024, 7(1), 276.
  • Walker L, Duncan R, Adamson B, Kendall H, Brittain N, Luzzi S, Jones D, Chaytor L, Peel S, Crafter C, O'Neill DJ, Gaughan L. Defining splicing factor requirements for androgen receptor variant synthesis in advanced prostate cancer. Molecular Cancer Research 2024, 22(12), 1128-1142.
  • Knutson TP, Luo B, Kobilka A, Lyman J, Guo S, Munro SA, Li Y, Heer R, Gaughan L, Morris MJ, Beltran H, Ryan CJ, Antonarakis ES, Armstrong AJ, Halabi S, Dehm SM. AR alterations inform circulating tumor DNA detection in metastatic castration resistant prostate cancer patients. Nature Communications 2024, 15, 10648.
  • Adamson B, Brittain N, Walker L, Duncan R, Luzzi S, Rescigno P, Smith GR, McGill S, Burchmore RJS, Willmore E, Hickson I, Robson CN, Bogdan D, Jimenez-Vacas JM, Paschalis A, Welti J, Yuan W, McCracken SR, Heer R, Sharp A, de Bono J, Gaughan L. The catalytic subunit of DNA-PK regulates transcription and splicing of AR in advanced prostate cancer. Journal of Clinical Investigation 2023, 133(22), e169200.
  • Harris RJ, Heer M, Levasseur MD, Cartwright TN, Weston B, Mitchell JL, Coxhead JM, Gaughan L, Prendergast L, Rico D, Higgins JMG. Release of Histone H3K4-reading transcription factors from chromosomes in mitosis is independent of adjacent H3 phosphorylation. Nature Communications 2023, 14, 7243.
  • Martinez RS, Salji MJ, Rushworth L, Ntala C, Blanco GR, Hedley A, Clark W, Peixoto P, Hervouet E, Renaude E, Kung SHY, Galbraith LCA, Nixon C, Lilla S, MacKay GM, Fazli L, Gaughan L, Sumpton D, Gleave ME, Zanivan S, Blomme A, Leung HY. SLFN5 regulates LAT1-Mediated mTOR activation in castration-resistant prostate cancer. Cancer Research 2021, 81(13), 3664-3678.
  • Hepburn AC, Curry EL, Moad M, Steele RE, Franco OE, Wilson L, Singh P, Buskin A, Crawford SE, Gaughan L, Mills IG, Hayward SW, Robson CN, Heer R. Propagation of human prostate tissue from induced pluripotent stem cells. Stem Cells Translational Medicine 2020, 9(7), 734-745.
  • Bainbridge A, Walker S, Smith J, Patterson K, Dutt D, Ng YM, Thomas HD, Wilson L, McCullough B, Jones D, Maan A, Banks P, McCracken SRC, Gaughan L, Robson CN, Coffey K. IKBKE activity enhances AR levels in advanced prostate cancer via modulation of the Hippo pathway. Nucleic Acids Research 2020, 48(10), 5366-5382.
  • Blomme A, Ford CA, Mui E, Patel R, Ntala C, Jamieson LE, Planque M, McGregor GH, Peixoto P, Hervouet E, Nixon C, Salji M, Gaughan L, Markert E, Repiscak P, Sumpton D, RodriguezBlanco G, Lilla S, Kamphorst JJ, Graham D, Faulds K, MacKay GM, Fendt SM, Zanivan S, Leung HY. 2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer. Nature Communications 2020, 11, 2508.
  • Chaytor L, Simcock M, Nakjang S, Heath R, Walker L, Robson C, Jones D, Gaughan L. The Pioneering Role of GATA2 in Androgen Receptor Variant Regulation Is Controlled by Bromodomain and Extraterminal Proteins in Castrate-Resistant Prostate Cancer. Molecular Cancer Research 2019, 17(6), 1264-1278.
  • Hepburn AC, Steele RE, Veeratterapillay R, Wilson L, Kounatidou EE, Barnard A, Berry P, Cassidy JR, Moad M, El-Sherif A, Gaughan L, Mills IG, Robson CN, Heer R. The induction of core pluripotency master regulators in cancers defines poor clinical outcomes and treatment resistance. Oncogene 2019, 38, 4412-4424.
  • Jones D, Wilson L, Thomas H, Gaughan L, Wade MA. The histone demethylase enzymes KDM3A and KDM4B co-operatively regulate chromatin transactions of the estrogen receptor in breast cancer. Cancers 2019, 11(8), 1122.
  • Fletcher CE, Sulpice E, Combe S, Shibakawa A, Leach DA, Hamilton MP, Chrysostomou SL, Sharp A, Welti J, Yuan W, Dart DA, Knight E, Ning J, Francis JC, Kounatidou EE, Gaughan L, Swain A, Lupold SE, de Bono JS, McGuire SE, Gidrol X, Bevan CL. Androgen receptor-modulatory microRNAs provide insight into therapy resistance and therapeutic targets in advanced prostate cancer. Oncogene 2019, 38, 5700-5724.
  • Kounatidou E, Nakjang S, McCracken SRC, Dehm SM, Robson CN, Jones D, Gaughan L. A novel CRISPR-engineered prostate cancer cell line defines the AR-V transcriptome and identifies PARP inhibitor sensitivities. Nucleic Acids Research 2019, 47(11), 5634-5647.
  • 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.
  • 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.
  • 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. Nucleic Acids Research 2017, 45(4), 1793-1804.
  • 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.
  • 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.
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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, 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.
  • 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. Regulation of gene expression by the RNA-binding protein Sam68 in cancer. Biochemical Society Transactions 2008, 36(3), 505-507.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

• Review

  • Buskin A, Scott E, Nelson R, Gaughan L, Robson CN, Heer R, Hepburn AC. Engineering prostate cancer in vitro: what does it take?. Oncogene 2023, 42, 2417–2427.