Staff Profile

INTRODUCTION

I obtained my PhD in Oncology from the Paterson Institute, Manchester, where I studied the use of modified DNA repair enzymes to reduce toxicity in patients undergoing chemotherapy. Following post-doctoral studies in the role of non-transcribed genes in breast cancer metastasis, I began my career in Drug Discovery with KuDOS Pharmaceuticals in Cambridge, UK. Working on PARP, DNA-PK, ATM and ATR in the DNA damage response field and mTOR survival signalling, I was responsible for bioscience in the discovery, translation and early clinical development programs leading to a number of small molecules that have undergone clinical testing. 

I moved to Belgium in 2008 to join Janssen Pharmaceutica, the European pharmaceutical division of Johnson and Johnson, and led drug discovery projects in the areas of kinase inhibition, deubiquitylases, protein:protein interactions, transcription factors and nuclear hormone receptors. I also provided preclinical bioscience support for the development of the HDAC inhibitor quisinostat and the prostate cancer therapeutics, Zytiga (abiraterone acetate) and apalutamide (ARN-509). In 2013, I moved to the US to lead Janssen’s small molecule bioscience for Prostate Cancer, work resulting in the discovery of a novel pan antagonist of the androgen receptor, TRC253.

I have 25 years of bioscience experience in Oncology research, over 15 years of which have been in drug discovery within the pharmaceutical industry; my goal now is to identify the next drugs to bring benefit to cancer patients. The CRUK Newcastle Drug Discovery unit are united in that goal!

ROLES AND RESPONSIBILITIES

• Drug Discovery Cancer Bioscience
• Responsible for Target Identification and Target Validation 
• Lead cancer target evaluation studies in a variety of tumours
• Development of cellular assays 

AREAS OF EXPERTISE

• Cancer cell signalling
• Cancer drug discovery and early development
• Small molecule inhibitors
• DNA repair
• Prostate cancer therapeutics
• Target validation
• Assay development

QUALIFICATIONS

• BSc (Hons) Biochemistry, Bath University, 1994
• PhD Oncology, University of Manchester, 1998

PREVIOUS POSITIONS

• Principal Scientist, Oncology Research, Janssen; 2013 – 2016, Spring House PA, USA
• Principal Scientist, Oncology Research, Janssen; 2008 – 2013, Beerse, Belgium
• Team Leader, KuDOS Pharmaceuticals, 2004 – 2008
• Senior Scientist, KuDOS Pharmaceuticals, 2000 – 2004

MEMBERSHIPS

• British Association for Cancer Research (BACR) - Executive Committee 2018-2021
• European Association for Cancer Research (EACR)
• American Association for Cancer Research (AACR)
• American Chemical Society (ACS)
• European School of Oncology (ESO)

Google Scholar: Click here.

SCOPUS: Click here.

• Al-Khawaldeh I, Aldred GG, Alyassiri M, Basmadjian C, Bordoni C, Harnor SJ, Heptinstall AB, Hobson SJ, Jennings CE, Khalifa S, Lebraud H, Miller DC, Shrives HJ, de Souza JV, Stewart HL, Temple M, Totobenazara J, Tucker JA, Tudhope SJ, Wang LZ, Bronowska AK, Cano C, Endicott JA, Golding BT, Hardcastle IR, Hickson I, Wedge SR, Willmore E, Noble MEM, Waring MJ. An alkynylpyrimidine-based covalent inhibitor that targets a unique cysteine in NF-κB-inducing kinase (NIK). Journal of Medicinal Chemistry 2021, 64(14), 10001-10018.
• Branch JR, Bush TL, Pande V, Connolly PJ, Zhang Z, Hickson I, Ondrus J, Jaensch S, Bischoff JR, Habineza G, van Hecke G, Meerpoel L, Packman K, Parrett CJ, Chong YT, Gottardis MM, Bignan G. Discovery of JNJ-63576253, a next-generation androgen receptor antagonist active against wild-type and clinically relevant ligand binding domain mutations in metastatic castration-resistant prostate cancer. Molecular Cancer Therapeutics 2021, 20(5), 763-774.
• Zhang Z, Connolly PJ, Lim HK, Pande V, Meerpoel L, Teleha C, Branch JR, Ondrus J, Hickson I, Bush T, Luistro L, Packman K, Bischoff JR, Ibrahim S, Parrett C, Chong Y, Gottardis MM, Bignan G. Discovery of JNJ-63576253: A Clinical Stage Androgen Receptor Antagonist for F877L Mutant and Wild-Type Castration-Resistant Prostate Cancer (mCRPC). Journal of Medicinal Chemistry 2021, 64(2), 909-924.
• Mesquita KA, Ali R, Doherty R, Toss MS, Miligy I, Alblihy A, Dorjsuren D, Simeonov A, Jadhav A, Wilson DM, Hickson I, Tatum NJ, Rakha EA, Madhusudan S. FEN1 Blockade for Platinum Chemo-Sensitization and Synthetic Lethality in Epithelial Ovarian Cancers. Cancers 2021, 13(8), 1866.
• Richters A, Doyle SK, Freeman DB, Lee C, Leifer BS, Jagannathan S, Kabinger F, Koren JV, Struntz NB, Urgiles J, Stagg RA, Curtin BH, Chatterjee D, Mathea S, Mikochik PJ, Hopkins TD, Gao H, Branch JR, Xin H, Westover L, Bignan GC, Rupnow BA, Karlin KL, Olson CM, Westbrook TF, Vacca J, Wilfong CM, Trotter BW, Saffran DC, Bischofberger N, Knapp S, Russo JW, Hickson I, Bischoff JR, Gottardis MM, Balk SP, Lin CY, Pop MS, Koehler AN. Modulating Androgen Receptor-Driven Transcription in Prostate Cancer with Selective CDK9 Inhibitors. Cell Chemical Biology 2021, 28, 1-14.
• Bignan G, Connolly PJ, Hickson I, Meerpoel L, Pande V, Zhang Z, Branch J, Rocaboy C, TrabalonEscolar LB. Substituted Thiohydantoin Derivatives as Androgen Receptor Antagonists. WO 2017/123542 A1, 20/07/2017.
• Bogner J, Zolghadr K, Hickson I, Romer T, Yurlova L. The fluorescent two-hybrid assay for live-cell profiling of androgen receptor modulators. The Journal of Steroid Biochemistry and Molecular Biology 2017, 166, 45-53.
• Branch J, Quigley M, Gottardis M, Hickson I. A high-throughput PPI assay to quantify inhibition of androgen receptor variant 7 (AR-V7) binding to canonical AR full-length (AR-FL) binding partners. In: AACR 107th Annual Meeting 2016. 2016, New Orleans, LA, USA: American Association for Cancer Research.
• Yurlova L, Buchfellner A, Gregor J, Romer T, Hickson I. Live-cell profiling of inhibitors targeting the N/C interaction within the androgen receptor. In: AACR 106th Annual Meeting 2015. 2015, Philadelphia, PA: AACR.
• Perez-Oliva AB, Lachaud C, Szyniarowski P, Muñoz I, Macartney T, Hickson I, Rouse J, Alessi DR. USP45 deubiquitylase controls ERCC1-XPF endonuclease mediated DNA damage responses. The EMBO Journal 2015, 34(3), 326-343.
• Moll JM, Teubel W, Hickson I, Graeser R, Jenster G, van Weerden W. In vitro co-culture model to study adrenal stimulus of CRPC. In: AUA Annual Meeting 2014. 2014, Orlando, Florida: Elsevier.
• Moll JM, Teubel W, Hickson I, Graeser R, Jenster G, vanWeerden W. Adrenal stimulation of CRPC growth in an in vitro co-culture model. In: Molecular Targets and Cancer Theraputics. 2014, Boston, MA, USA: AACR.
• Vidic S, Esser N, de Hoogt R, Verberne I, Kogan-Sakin I, Stein Y, Rotter V, Barbier M, Chong Y, Breucker SD, Smans K, Akerfelt M, Nees M, King P, Hickson I, van Weerden W, Graeser R. Complex in vitro and in vivo prostate cancer models for the PREDECT consortium. In: AACR Annual Meeting 2014. 2014, San Diego, CA: AACR.
• Yurlova L, Brown CJ, Derks M, Ghadessy FJ, Hickson I, Lane DP, Krausz E, Zolghadr K. Disrupting p53:Mdm2 and p53:Mdm4 - Comparative cell-based assays for drug screening. In: AACR Annual Meeting 2014. 2014, San Diego, CA: AACR.
• Carol H, Gorlick R, Kolb EA, Morton CL, Manesh DM, Keir ST, Reynolds CP, Kang MH, Maris JM, Wozniak A, Hickson I, Lyalin D, Kurmasheva RT, Houghton PJ, Smith MA, Lock R. Initial testing (stage 1) of the histone deacetylase inhibitor, quisinostat (JNJ-26481585), by the Pediatric Preclinical Testing Program. Pediatric Blood and Cancer 2014, 61(2), 245-252.
• Yurlova L, Derks M, Buchfellner A, Hickson I, Janssen M, Morrison D, Stansfield I, Brown CJ, Ghadessy FJ, Lane DP, Rothbauer U, Zolghadr K, Krausz E. The Fluorescent Two-Hybrid Assay to Screen for Protein–Protein Interaction Inhibitors in Live Cells: Targeting the Interaction of p53 with Mdm2 and Mdm4. Journal of Biomolecular Screening 2014, 19(4), 516-525.
• Foote K, Blades K, Cronin A, Fillery S, Guichard SS, Hassall L, Hickson I, Jacq X, Jewsbury PJ, McGuire TM, Nissink JW, Odedra R, Page K, Perkins P, Suleman A, Tam K, Thommes P, Broadhurst R, Wood C. Discovery of 4-{4-[(3R)-3-Methylmorpholin-4-yl]-6-[1-(methylsulfonyl)cyclopropyl]pyrimidin-2-yl}-1H-indole (AZ20): a potent and selective inhibitor of ATR protein kinase with monotherapy in vivo antitumor activity. J Med Chem 2013, 56(5), 2125–2138.
• Hickson I, Marien A, Derks M, Janssen M. Assessment of abiraterone (ABI) tumor cell activity via in vitro models of androgen (A)-responsive prostate cancer. In: 48th Annual Meeting of the American-Society-of-Clinical-Oncology. 2012, Chicago, IL: ASCO.
• Chresta CM, Davies BR, Hickson I, Harding T, Cosulich S, Critchlow SE, Vincent JP, Ellston R, Jones D, Sini P, James D, Howard Z, Dudley P, Hughes G, Smith L, Maguire S, Hummersone M, Malagu K, Menear K, Jenkins R, Jacobsen M, Smith GC, Guichard S, Pass M. AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity. Cancer Research 2010, 70(1), 288-298.
• Menear KA, Gomez S, Malagu K, Bailey C, Blackburn K, Cockcroft XL, Ewen S, Fundo A, LeGall A, Hermann G, Sebastian L, Sunose M, Presnot T, Torode E, Hickson I, Martin NM, Smith GC, Pike KG. Identification and optimisation of novel and selective small molecular weight kinase inhibitors of mTOR. Biorganic & Medicinal Chemistry Letters 2009, 19(20), 5898-5901.
• Arts J, King P, Marien A, Floren W, Belien A, Janssen L, Pilatte I, Roux B, Decrane L, Gilissen R, Hickson I, Vreys V, Cox E, Bol K, Talloen W, Goris I, Andries L, DuJardin M, Janicot M, Page M, vanEmelen K, Angibaud P. JNJ-26481585, a novel "second-generation" oral histone deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity. Clinical Cancer Research 2009, 15(22), 6841-6851.
• Malagu K, Duggan H, Menear K, Hummersone M, Gomez S, Bailey C, Edwards P, Drzewiecki J, Leroux F, Quesada MJ, Hermann G, Maine S, Molyneaux CA, LeGall A, Pullen J, Hickson I, Smith L, Maguire S, Martin N, Smith G, Pass M. The discovery and optimisation of pyrido[2,3-d]pyrimidine-2,4-diamines as potent and selective inhibitors of mTOR kinase. Bioorganic & Medicinal Chemistry Letters 2009, 19(20), 5950-5953.
• Hollick J, Rigoreau L, Cano-Soumillac C, Cockcroft X, Curtin NJ, Frigerio M, Golding BT, Guiard S, Hardcastle IR, Hickson I, Hummersone M, Menear K, Martin N, Matthews I, Newell DR, Ord R, Richardson C, Smith G, Griffin RJ. Pyranone, thiopyranone, and pyridone inhibitors of phosphatidylinositol 3-kinase related kinases. Structure-activity relationships for DNA-dependent protein kinase inhibition, and identification of the first potent and selective inhibitor of the ataxia telangiectasia mutated kinase. Journal of Medicinal Chemistry 2007, 50(8), 1958-1972.
• Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, Martin NM, Jackson SP, Smith GC, Ashworth A. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005, 434(7035), 917-921.
• Hickson, I., Zhao, Y., Richardson, C., Green, S., Martin, N., Orr, A., Reaper, P., Jackson, S., Curtin, N.J., Smith, G. Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM. Cancer Research 2004, 64(24), 9152-9159.