Hing Leung - Prostate Cancer Biology

Introduction

Leung Hing 0020

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

2018

Altwaijry N, Somani S, Parkinson JA, Tate RJ, Keating P, Warzecha M, Mackenzie GR, Leung HY, Dufes C. Regression of prostate tumors after intravenous administration of lactoferrin-bearing polypropylenimine dendriplexes encoding TNF-alpha, TRAIL, and interleukin-12. Drug Deliv 2018;25(1):679-89. doi: 10.1080/10717544.2018.1440666

Galbraith L, Leung HY, Ahmad I. Lipid pathway deregulation in advanced prostate cancer. Pharmacol Res 2018;131:177-84. doi: 10.1016/j.phrs.2018.02.022

Patel R, Fleming J, Mui E, Loveridge C, Repiscak P, Blomme A, Harle V, Salji M, Ahmad I, Teo K, Hamdy FC, Hedley A, van den Broek N, Mackay G, Edwards J, et al. Sprouty2 loss-induced IL6 drives castration-resistant prostate cancer through scavenger receptor B1. EMBO Mol Med 2018;10(4). doi: 10.15252/emmm.201708347

2017

Loveridge CJ, Mui EJ, Patel R, Tan EH, Ahmad I, Welsh M, Galbraith J, Hedley A, Nixon C, Blyth K, Sansom O, Leung HY. Increased T-cell Infiltration Elicited by Erk5 Deletion in a Pten-Deficient Mouse Model of Prostate Carcinogenesis. Cancer Res 2017; 77: 3158-68

Loveridge CJ, van 't Hof RJ, Charlesworth G, King A, Tan EH, Rose L, Daroszewska A, Prior A, Ahmad I, Welsh M, Mui EJ, Ford C, Salji M, Sansom O, Blyth K, Leung HY. Analysis of Nkx3.1:Cre-driven Erk5 deletion reveals a profound spinal deformity which is linked to increased osteoclast activity. Sci Rep 2017; 7: 13241

Munkley J, McClurg UL, Livermore KE, Ehrmann I, Knight B, McCullagh P, McGrath J, Crundwell M, Harries LW, Leung HY, Mills IG, Robson CN, Rajan P, Elliott DJ. The cancer-associated cell migration protein TSPAN1 is under control of androgens and its upregulation increases prostate cancer cell migration. Sci Rep 2017; 7: 5249

Patek S, Willder J, Heng J, Taylor B, Horgan P, Leung H, Underwood M, Edwards J. Androgen receptor phosphorylation status at serine 578 predicts poor outcome in prostate cancer patients. Oncotarget 2017; 8: 4875-87

Salji M, Hendry J, Patel A, Ahmad I, Nixon C, Leung HY. Peri-prostatic Fat Volume Measurement as a Predictive Tool for Castration Resistance in Advanced Prostate Cancer. Eur Urol Focus 2017 Mar 1. pii: S2405-4569(17)30028-7. doi: 10.1016/j.euf.2017.01.019. [Epub ahead of print]

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

Lab Members

leung group

Associate Scientist

Rachana Patel

Post-docs

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

Senior Scientific Officer

Catriona Ford
Ee Hong Tan

Scientific Officers

Carolyn Loveridge
Ernest Mui

Technicians/Research Associates

Victoria Harle (Prostate Cancer Foundation USA)
Linda Rushworth (Prostate Cancer Foundation USA)

Clinical Research Fellow

Chara Ntala

PhD Student

Rafael Sanchez (TransPot, EU)

Research

At the bench 3 160

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

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Seminars

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

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