Hing Leung - Prostate Cancer Biology

Introduction

leung

Prostate cancer is a major global health issue, and its management remains controversial. A refined understanding of how aberrant signalling drives prostate carcinogenesis will help develop better prognostic biomarkers and therapeutic targets. FGF receptor and ERK5 in particular have been implicated in prostate cancer.

Work in our lab continues to explore the significance of these signalling pathways, to investigate tumour biology using in vitro and in vivo models and to develop specific small molecule inhibitors. Working closely with colleagues in the NHS, Glasgow University and the Beatson Institute, we are developing infrastructure required for the necessary biorespository and other ongoing translational research programmes.

Potential Post-docs, Clinical Fellows and Students

We are always keen to hear from good people. Please email me (h.leung@beatson.gla.ac.uk) with a copy of your CV including the details of two referees.

Lab Report

Key Publications

Patel R, Gao M, Ahmad I, Fleming J, Singh LB, Rai TS, McKie AB, Seywright M, Barnetson RJ, Edwards J, Sansom OJ and Leung HY. Sprouty2, PTEN and PP2A interact to regulate prostate cancer progression. Journal of Clinical Investigation 123(3): 1157-75, 2013

Gao M, Patel R, Ahmad I, Fleming J, Edwards J, McCracken S, Sahadevan K, Seywright M, Norman J, Sansom O, Leung HY. SPRY2 loss enhances ErbB trafficking and PI3K/AKT signalling to drive human and mouse prostate carcinogenesis. EMBO Mol Med. 4(8): 776-90, 2012

Ahmad I, Patel R, Singh LB, Nixon C, Seywright M, Barnetson RJ, Brunton V, Muller WJ, Edwards J, Sansom OJ, Leung HY. HER2 overcomes PTEN (loss) induced Senescence to cause Aggressive Prostate Cancer. Proc Nat Acad Sci 108(39): 6392-7, 2011

Ahmad I, Morton J, Singh BL, Radulescu SM, Ridgway RA, Patel S, Woodgett J, D, Winton DL, Taketo MM, Wu XR Leung HY, Sansom OJ. β-catenin activation synergises with PTEN loss to cause bladder cancer formation. Oncogene 30: 178-89, 2011

Wiltshire C, Singh BL, Stockley J, Fleming J, Doyle B, Barnetson R, Robson CN, Kozielski F and Leung HY. Docetaxel resistant prostate cancer cells remain sensitive to S-trityl L-cysteine (STLC) mediated Eg5 inhibition. Mol Cancer Therapeutics 9: 1730-9, 2010

McCracken SR, Ramsay A, Heer R, Mathers ME, Jenkins BL, Edwards J, Robson CN, Marquez R, Cohen P, Leung HY. Aberrant expression of extracellular signal-regulated kinase 5 in human prostate cancer. Oncogene 27: 2978-88, 2008

Biography

Education and qualifications

1986: MB ChB, University of Aberdeen
1990: FRCS (Glas) , Royal College of Physicians and Surgeons of Glasgow
1994: PhD, University of London, Supervisor Nick Lemoine
1997: FRCS (Urol), Royal Colleges of Surgeons (UK & Ireland)

Appointments

2006-present: Professor of Urology and Surgical Oncology, University of Glasgow; Group Leader, CRUK Beatson Institute; Consultant Urological Surgeon, NHS Greater Glasgow and Clyde
2002-2006: Professor of Urological Oncology, University of Newcastle upon Tyne
1999-2002: Senior Lecturer, University of Newcastle upon Tyne
1995-1998: Clinical Lecturer, University of Newcastle upon Tyne
1990-1994: Clinical Research Fellow, Imperial Cancer Research Fund
1987-1989: Surgical Registrar, Birmingham Rotation

Current committee membership

Movember GAP Committee
Prostate Cancer UK Trustee
Chairman, Section of Academic Urology, British Association of Urological Surgeons
MRC College of Experts & Molecular and Cellular Medicine Board

Honours and awards

The Karl Storz Harold Hopkins Golden Telescope Award, British Association of Urological Surgeons, 2008
Founding member of the Northern Institute for Cancer Research, University of Newcastle upon Tyne

Recent Publications

2016

Ahmad I, Mui E, Galbraith L, Patel R, Tan EH, Salji M, Rust AG, Repiscak P, Hedley A, Markert E, Loveridge C, van der Weyden L, Edwards J, Sansom OJ, Adams DJ, Leung HY. Sleeping Beauty screen reveals Pparg activation in metastatic prostate cancer. Proc Natl Acad Sci USA 113: 8290-5, 2016

Kerr L, Rewhorn MJ, Longmuir M, Fraser S, Walsh S, Andrew N, Leung HY. A cohort analysis of men with a family history of BRCA1/2 and Lynch mutations for prostate cancer. BMC cancer 16: 529, 2016

Munkley J, Vodak D, Livermore KE, James K, Wilson BT, Knight B, McCullagh P, McGrath J, Crundwell M, Harries LW, Leung HY, Robson CN, Mills IG, Rajan P, Elliott DJ (2016) Glycosylation is an Androgen-Regulated Process Essential for Prostate Cancer Cell Viability. EBioMedicine 8: 103-16, 2016

Myers SM, Bawn RH, Bisset LC, Blackburn TJ, Cottyn B, Molyneux L, Wong AC, Cano C, Clegg W, Harrington RW, Leung H, Rigoreau L, Vidot S, Golding BT, Griffin RJ, Hammonds T, Newell DR, Hardcastle IR. High-throughput screening and hit validation of extracellular-related kinase 5 (ERK5) inhibitors. ACS Comb Sci 18: 444-55, 2016

Peck B, Schug ZT, Zhang Q, Dankworth B, Jones DT, Smethurst E, Patel R, Mason S, Jiang M, Saunders R, Howell M, Mitter R, Spencer-Dene B, Stamp G, McGarry L, James D, Shanks E, Aboagye EO, Critchlow SE, Leung HY Harris AL, Wakelam MJ, Gottlieb E, Schulze A. Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments. Cancer & metabolism 4: 6, 2016

2015

Mardilovich K, Gabrielsen M, McGarry L, Orange C, Patel R, Shanks E, Edwards J, Olson MF. Elevated LIM kinase 1 in non-metastatic prostate cancer reflects its role in facilitating androgen receptor nuclear translocation. Mol Cancer Ther 14: 246-58, 2015

Munkley J, Lafferty NP, Kalna G, Robson CN, Leung HY, Rajan P, Elliott DJ. Androgen-regulation of the protein tyrosine phosphatase PTPRR activates ERK1/2 signalling in prostate cancer cells. BMC Cancer 15: 9, 2015

Munkley J, Oltean S, Vodak D, Wilson BT, Livermore KE, Zhou Y, Star E, Floros VI, Johannessen B, Knight B, McCullagh P, McGrath J, Crundwell M, Skotheim RI, Robson CN, Leung HY, Harries LW, Rajan P, Mills IG, Elliott DJ. The androgen receptor controls expression of the cancer-associated sTn antigen and cell adhesion through induction of ST6GalNAc1 in prostate cancer. Oncotarget 6: 34358-74, 2015

Rajan P, Frew JA, Wilson JM, Azzabi AS, McMenemin RM, Stockley J, Soomro NA, Durkan G, Pedley ID, Leung HY. Feasibility study of a randomized controlled trial comparing docetaxel chemotherapy and androgen deprivation therapy with sequential prostatic biopsies from patients with advanced non-castration-resistant prostate cancer. Urol Oncol 33: 337.e1-6, 2015

Stockley J, Markert E, Zhou Y, Robson CN, Elliott DJ, Lindberg J, Leung HY, Rajan P. The RNA-binding protein Sam68 regulates expression and transcription function of the androgen receptor splice variant AR-V7. Sci Rep 5: 13426, 2015

Brzezinska EA, Nixon C, Patel R, Leung HY. Genetically engineered mouse models to study prostate cancer. Methods Mol Biol 1267: 73-91, 2015

Choudhury Y, Salt IP, Leung HY. AMPK-friend or foe for targeted therapy? Cell Cycle 14: 1761-2, 2015

2014

Foth M, Ahmad I, van Rhijn BW, van der Kwast T, Bergman AM, King L, Ridgway R, Leung HY, Fraser S, Sansom OJ, Iwata T. Fibroblast growth factor receptor 3 activation plays a causative role in urothelial cancer pathogenesis in cooperation with Pten loss in mice. J Pathol 233: 148-58, 2014

Li A, Morton JP, Ma Y, Karim SA, Zhou Y, Faller WJ, Woodham EF, Morris HT, Stevenson RP, Juin A, Jamieson NB, MacKay CJ, Carter CR, Leung HY, Yamashiro S, Blyth K, Sansom OJ, Machesky LM. Fascin is regulated by slug, promotes progression of pancreatic cancer in mice, and is associated with patient outcomes. Gastroenterology 2014; 146: 1386-96 e1-17, 2014

Munkley J, Rajan P, Lafferty NP, Dalgliesh C, Jackson RM, Robson CN, Leung HY, Elliott DJ. A novel androgen-regulated isoform of the TSC2 tumour suppressor gene increases cell proliferation. Oncotarget 5: 131-9, 2014

Noble-Jones R, Fitzpatrick B, Sneddon MC, Hendry DS, Leung HY. Development of the lymphoedema genito-urinary cancer questionnaire. Br J Nurs 23 Suppl 18: S14-9, 2014

Salji M, Jones R, Paul J, Birrell F, Dixon-Hughes J, Hutchison C, Johansen TE, Greene D, Parr N, Leung HY. Feasibility study of a randomised controlled trial to compare (deferred) androgen deprivation therapy and cryotherapy in men with localised radiation-recurrent prostate cancer. Br J Cancer 111: 424-9, 2014

Stockley J, Villasevil ME, Nixon C, Ahmad I, Leung HY, Rajan P. The RNA-binding protein hnRNPA2 regulates beta-catenin protein expression and is overexpressed in prostate cancer. RNA Biol 2014; 11: 755-65, 2014

Mukherjee A, Morton S, Fraser S, Salmond J, Baxter G, Leung HY. Magnetic resonance imaging-directed transperineal limited-mapping prostatic biopsies to diagnose prostate cancer: a Scottish experience. Scott Med J 59: 204-8, 2014

2013

Ahmad I, Gao M, Patel R, Leung HY. Modelling synergistic interactions between HER2, Sprouty2 and PTEN in driving prostate carcinogenesis. Asian J Androl 15: 323-7, 2013

Ahmad I, Kalna G, Ismail M, Birrell F, Asterling S, McCartney E, Greene D, Davies J, Leung HY. Prostate gland lengths and iceball dimensions predict micturition functional outcome following salvage prostate cryotherapy in men with radiation recurrent prostate cancer. PLoS One 8: e69243, 2013

Ahmad I, Singh LB, Yang ZH, Kalna G, Fleming J, Fisher G, Cooper C, Cuzick J, Berney DM, Møller H, Scardino P and Leung HY. Mir143 expression inversely correlates with nuclear ERK5 immunoreactivity in clinical prostate cancer. Br J Cancer 108: 149–54, 2013

Bennett HL, Stockley J, Fleming JT, Mandal R, O'Prey J, Ryan KM, Robson CN, Leung HY. Does androgen-ablation therapy (AAT) associated autophagy have a pro-survival effect in LNCaP human prostate cancer cells? BJU Int 111(4): 672-82, 2013

Forbat L, Place M, Kelly D, Hubbard G, Boyd K, Howie K, Leung HY. A cohort study reporting clinical risk factors and individual risk perceptions of prostate cancer: Implications for PSA testing. BJU Int 111(3): 389-95, 2013

Patel R, Gao M, Ahmad I, Fleming J, Singh LB, Rai TS, McKie AB, Seywright M, Barnetson RJ, Edwards J, Sansom OJ and Leung HY. Sprouty2, PTEN and PP2A interact to regulate prostate cancer progression. J Clin Invest 123(3): 1157-75, 2013

Willder JM, Heng SJ, McCall P, Adams CE, Tannahill C, Fyffe G, Seywright M, Horgan PG, Leung HY, Underwood MA, Edwards J. Androgen receptor phosphorylation at serine 515 by Cdk1 predicts biochemical relapse in prostate cancer patients. Br J Cancer 108(1): 139-48, 2013

Yang Z, Laird A, Monaghan A, Seywright M and Leung HY. Incidental seminal vesicle amyloidosis at the same time of diagnostic prostatic biopsies – Is routine investigations for systemic amyloidosis warranted? Asian Journal of Andrology Asian J 15: 149-151, 2013

Rajan P, Leung HY. Lecture Notes in Clinical Pharmacology and Therapeutics 9th edition. (Eds: Gerard A. McKay & Matthew R. Walters). Wiley-Blackwell ISBN 9781118344811, 2013

Rajan P, Sudbery IM, Villasevil ME, Mui E, Fleming J, Davis M, Ahmad I, Edwards J, Sansom OJ, Sims D, Ponting CP, Heger A, McMenemin RM, Pedley ID, Leung HY. Next-generation Sequencing of Advanced Prostate Cancer Treated with Androgen-deprivation Therapy. Eur Urol, in press 2013

Zhang T, Watson DG, Wang L, Abbas M, Murdoch L, Bashford L, Ahmad I, Lam NY, Ng AC, Leung HY. Application of Holistic Liquid Chromatography-High Resolution Mass Spectrometry Based Urinary Metabolomics for Prostate Cancer Detection and Biomarker Discovery. PLoS One 2013; 8: e65880. Epub 2013/07/05.Zhang T, Watson DG, Wang L, Abbas M, Murdoch L, Bashford L, Ahmad I, Lam N-Y, Ng ACF, Leung HY. Application of Holistic Liquid Chromatography-Mass Spectrometry based Urinary Metabolomics for Prostate Cancer Detection and Biomarker Discovery Plos One, in press 2013

Forbat L, Place M, Hubbard G, Leung H, Kelly D. The role of interpersonal relationships in men's attendance in primary care: qualitative findings in a cohort of men with prostate cancer. Support Care Cancer, in press 2013

Neuhaus J, Schiffer E, von Wilcke P, Bauer HW, Leung H, Siwy J, Ulrici W, Paasch U, Horn LC, Stolzenburg JU. Seminal plasma as a source of prostate cancer peptide biomarker candidates for detection of indolent and advanced disease. PLoS One 8: e67514, 2013

Shafique K, Proctor MJ, McMillan DC, Leung H, Smith K, Sloan B, Morrison DS. The modified Glasgow prognostic score in prostate cancer: results from a retrospective clinical series of 744 patients. BMC Cancer 13: 292, 2013

2012

Ahmad I, Small DR, Krishna NS, Akhtar MN, Leung HY. Prostate cancer incidence in patients on 5α-reductase inhibitors for lower urinary tract symptoms: A 14-year retrospective study. British Journal of Medical and Surgical Urology 5(4): 179–83, 2012

Gao M, Patel R, Ahmad I, Fleming J, Edwards J, McCracken S, Sahadevan K, Seywright M, Norman J, Sansom O, Leung HY. SPRY2 loss enhances ErbB trafficking and PI3K/AKT signalling to drive human and mouse prostate carcinogenesis. EMBO Mol Med 4(8): 776-90, 2012

Kelly JD, Dudderidge TJ, Wollenschlaeger A, Okoturo O, Burling K, Tulloch F, Halsall I, Prevost T, Prevost AT, Vasconcelos JC, Robson W, Leung HY, Vasdev N, Pickard RS, Williams GH, Stoeber K. Bladder cancer diagnosis and identification of clinically significant disease by combined urinary detection of mcm5 and nuclear matrix protein 22. PLoS One 7(7): e40305, 2012

McCall P, Bennett L, Ahmad I, Mackenzie LM, Forbes IW, Leung HY, Sansom OJ, Orange C,Seywright M, Underwood MA, Edwards J. NFkappaB signalling is upregulated in a subset of castrate-resistant prostate cancer patients and correlates with disease progression. Br J Cancer 107: 1554-63, 2012

Shafique K, McLoone P, Qureshi K, Leung H, Hart C, Morrison DS. Cholesterol and the risk of grade-specific prostate cancer incidence: evidence from two large prospective cohort studies with up to 37 years' follow up. BMC Cancer 12: 25, 2012

Shafique K, McLoone P, Qureshi K, Leung H, Hart C, Morrison DS. Tea Consumption and the Risk of Overall and Grade Specific Prostate Cancer: A Large Prospective Cohort Study of Scottish Men. Nutr Cancer 64: 790-7, 2012

Shafique K, McLoone P, Qureshi K, Leung H, Hart C, Morrison D. Coffee consumption and prostate cancer risk: further evidence for inverse relationship. Nutr J 11(1): 42, 2012

Williamson SC, Hepburn AC, Wilson L, Coffey K, Ryan-Munden CA, Pal D, Leung HY, Robson CN, Heer R. Human α(2)β(1) (HI) CD133(+VE) Epithelial Prostate Stem Cells Express Low Levels of Active Androgen Receptor. PLoS One 7(11): e48944, 2012

Ahmad I, Iwata T, Leung HY. Mechanisms of FGFR-mediated carcinogenesis. Biochim Biophys Acta 1823: 850-60, 2012

Ahmad I, Sansom OJ, Leung HY. Exploring molecular genetics of bladder cancer: lessons learned from mouse models. Dis Model Mech 5(3): 323-32, 2012

Krishnan A, Wilson J, Leung HY. Approaches for Developing Novel Microtubule Targeting Agents (MTas) for Therapeutic Exploitation. Curr Pharm Des 18: 2804-10, 2012

Mischak H, Ioannidis JP, Argiles A, Attwood TK, Bongcam-Rudloff E, Broenstrup M, Charonis A, Chrousos GP, Delles C, Dominiczak A, Dylag T, Ehrich J, Egido J, Findeisen P, Jankowski J, Johnson RW, Julien BA, Lankisch T, Leung HY, Maahs D, Magni F, Manns MP, Manolis E, Mayer G, Navis G, Novak J, Ortiz A, Persson F, Peter K, Riese HH, Rossing P, Sattar N, Spasovski G, Thongboonkerd V, Vanholder R, Schanstra JP, Vlahou A. Implementation of proteomic biomarkers: making it work. Eur J Clin Invest 42(9): 1027-36, 2012

Patel R, Leung HY. Targeting the EGFR-family for Therapy: Biological Challenges and Clinical Perspective. Curr Pharm Des 18: 2672-9, 2012

Williamson SC, Mitter R, Hepburn AC, Wilson L, Mantilla A, Leung HY, Robson CN, Heer R. Characterisations of human prostate stem cells reveal deficiency in class I UGT enzymes as a novel mechanism for castration-resistant prostate cancer. Br J Cancer 109: 950-6, 2013

Lab Members

leung group

Associate Scientist

Rachana Patel

Post-docs

Arnaud Blomme
Peter Repiscak (Bioinformatician, Prostate Cancer Foundation USA)

Scientific Officers

Catriona Ford
Ee Hong Tan

Technicians/Research Associates

Victoria Harle (Prostate Cancer Foundation USA)
Carolyn Loveridge (Prostate Cancer UK)
Ernest Mui (Prostate Cancer Foundation USA)
Linda Rushworth (Prostate Cancer Foundation USA)

Clinical Research Fellow

Mark Salji (MRC)

PhD Student

Calum Johnston
Rafael Sanchez (TransPot, EU)

Research

lab image 2017 2

Read more about the Research Groups working at the Beatson Institute.

More

Seminars

lab image 2017

Find out more about our seminars including our Distinguished Seminar Programme.

More