Medicine

Simon Crabb

BSc, MBBS, MRCP, PhD

Primary position:
Senior Lecturer in Medical Oncology

Background

The University of Southampton

Dr Crabb graduated in medicine from St George’s Hospital Medical School, London in 1996. He joined the University of Southampton in 2002 as a Cancer Research UK Clinical Research Fellow and was awarded his PhD in 2006 for work involving novel histone deacetylase inhibitors. Following a Clinical Research Fellowship at the BC Cancer Agency in Vancouver, he returned to the Cancer Sciences Unit in Southampton and was appointed as a Senior Lecturer and Honorary Consultant in Medical Oncology in 2009.

Dr Crabb’s work is divided between his research interests and the Department of Medical Oncology at University Hospital Southampton NHS Foundation Trust where he specialises in the management of genitourinary cancers. His research interests are in epigenetic therapeutic agents, mechanisms of chemotherapy resistance and the development of molecularly targeted therapeutic strategies for genitourinary cancers. In addition to laboratory work, he is an active clinical researcher leading and participating in a number of early phase clinical trials for genitourinary cancers.

Qualifications

BSc, Biochemistry, University of London, 1993
MBBS, Medicine, University of London, 1996
MRCP, Royal College of Physicians, 2000
PhD, University of Southampton, 2006

Appointments held

Senior Lecturer in Medical Oncology, University of Southampton Faculty of Medicine

Honorary Consultant in Medical Oncology, University Hospital Southampton NHS Foundation Trust

Dr Simon Crabb's photo

Publications

The University of Southampton's electronic library (e-prints)

Article

Gurung, Pratik M.S., Veerakumarasivam, Abhi, Williamson, Magali, Counsell, Nicholas, Douglas, James, Tan, Wei S., Feber, Andrew, Crabb, Simon J., Short, Susan C., Freeman, Alex, Powles, Thomas, Hoskin, Peter J., West, Catharine M. and Kelly, John D. (2014) Loss of expression of the tumour suppressor gene AIMP3 predicts survival following radiotherapy in muscle-invasive bladder cancer. International Journal of Cancer, 1-40. (doi:10.1002/ijc.29022). (PMID:24917520).
Powles, Thomas, Foreshew, Shah-Jalal Sarker, Shamash, Jonathan, Sarwar, Naveed, Crabb, Simon, Sahdev, Anju, Nixon, Jude, Lim, Louise, Pungaliya, Ashish, Foreshaw, Abigail, Davies, Rachel, Greenwood, Michelle, Wilson, Peter, Pacey, Simon, Galazi, Myra, Jones, Robert and Chowdhury, Simon (2014) A phase Ib study investigating the combination of everolimus and dovitinib in vascular endothelial growth factor refractory clear cell renal cancer. European Journal of Cancer, 1-8. (doi:10.1016/j.ejca.2014.04.021). (PMID:24908540).
Hayden, Annette, Douglas, James, Sommerlad, Matthew, Andrews, Lawrence, Gould, Katherine, Hussain, Syed, Thomas, Gareth J, Packham, Graham and Crabb, Simon J (2014) The Nrf2 transcription factor contributes to resistance to cisplatin in bladder cancer. Urologic Oncology (doi:10.1016/j.urolonc.2014.02.006). (PMID:24837013).
Douglas, J., Sharp, A., Chau, C., Head, J., Drake, T., Wheater, M., Geldart, T., Mead, G. and Crabb, S.J. (2014) Serum total hCGβ level is an independent prognostic factor in transitional cell carcinoma of the urothelial tract. British Journal of Cancer, 110, (7), 1759-1766. (doi:10.1038/bjc.2014.89). (PMID:24556622).
Tortorici, Marcello, Borrello, Maria Teresa, Tardugno, Maria, Chiarelli, Laurent R., Pilotto, Simona, Ciossani, Giuseppe, Vellore, Nadeem A., Bailey, Sarah G., Cowan, Jonathan, O'Connell, Maria, Crabb, Simon J., Packham, Graham, Mai, Antonello, Baron, Riccardo, Ganesan, A. and Mattevi, Andrea (2013) Protein recognition by short peptide reversible inhibitors of the chromatin-modifying LSD1/CoREST lysine demethylase. ACS Chemical Biology, 8, (8), 1677-1682. (doi:10.1021/cb4001926). (PMID:23721412).
Pienta, Kenneth J., Machiels, Jean-Pascal, Schrijvers, Dirk, Alekseev, Boris, Shkolnik, Mikhail, Crabb, Simon J., Li, Susan, Seetharam, Shobha, Puchalski, Thomas A., Takimoto, Chris, Elsayed, Yusri, Dawkins, Fitzroy and de Bono, Johann S. (2012) Phase 2 study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 (CCL2), in metastatic castration-resistant prostate cancer. Investigational New Drugs (doi:10.1007/s10637-012-9869-8). (PMID:22907596).
Crabb, Simon J., Bradbury, J., Nolan, L., Selman, D., Muthuramalingam, Sethupathi R., Cave, Judith, Johnson, Peter W.M. and Ottensmeier, Christian (2012) A phase I clinical trial of Irinotecan and Carboplatin in patients with extensive stage small cell lung cancer. Chemotherapy, 58, (4), 257-263. (doi:10.1159/000341274). (PMID:22907396).
Crabb, Simon J., Bradbury, Jennifer, Nolan, Luke, Selman, Diana, Muthuramalingam, Sethupathi R., Cave, Judith, Johnson, Peter W.M. and Ottensmeier, Christian (2012) A phase I clinical trial of irinotecan and carboplatin in patients with extensive stage small cell lung cancer. Chemotherapy, 58, (4), 257-263. (doi:10.1159/000341274). (PMID:22907396).
Powles, Thomas, Sarwar, Naveed, Jones, Rob, Wilson, Peter, Boleti, Ekaterini, Protheroe, Andrew, Crabb, Simon J, Shamash, Jonathan, Stockdale, Andrew, Rashid, Sukaina, Nathan, Paul and Chowdury, Simon (2012) An indirect comparison of the toxicity of sunitinib and pazopanib in metastatic clear cell renal cancer. European Journal of Cancer (doi:10.1016/j.ejca.2012.05.022). (PMID:22766517).
Hayden, Annette, Johnson, Peter W.M., Packham, Graham and Crabb, Simon J. (2011) S-adenosylhomocysteine hydrolase inhibition by 3-deazaneplanocin A analogues induces anti-cancer effects in breast cancer cell lines and synergy with both histone deacetylase and HER2 inhibition. Breast Cancer Research and Treatment, 127, (1), 109-119. (doi:10.1007/s10549-010-0982-0). (PMID:20556507).
Benelkebir, Hanae, Marie, Sabrina, Hayden, Annette L., Lyle, Jason, Loadman, Paul M, Crabb, Simon J., Packham, Graham and Ganesan, A. (2011) Total synthesis of largazole and analogues: HDAC inhibition, antiproliferative activity and metabolic stability. Bioorganic & Medicinal Chemistry (doi:10.1016/j.bmc.2011.02.024). (PMID:21420302).
Benelkebir, Hanae, Hodgkinson, Christopher, Duriez, Patrick J., Hayden, Annette L., Bulleid, Rosemary A., Crabb, Simon J., Packham, Graham and Ganesan, A. (2011) Enantioselective synthesis of tranylcypromine analogues as lysine demethylase (LSD1) inhibitors. Bioorganic & medicinal chemistry (doi:10.1016/j.bmc.2011.02.017). (PMID:21382717).
Crabb, Simon J. and Wheater, Matthew J. (2010) Advances in chemotherapy and targeted systemic therapies for Urothelial cancer. Current Drug Therapy, 5, (1), 17-28.
Ganesan, A., Nolan, L., Crabb, S.J. and Packham, G. (2009) Epigenetic therapy: histone acetylation, DNA methylation and anti-cancer drug discovery. Current Cancer Drug Targets, 9, (8), 963-981.
Sharp, Adam, Crabb, Simon J., Johnson, Peter W.M., Hague, Angela, Cutress, Ramsey, Townsend, Paul A., Ganesan, A. and Packham, Graham (2009) Thioflavin S (NSC71948) interferes with Bcl-2-associated athanogene (BAG-1)-mediated protein-protein interactions. Journal of Pharmacology and Experimental Therapeutics, 331, (2), 680-689. (doi:10.1124/jpet.109.153601).
Crabb, S.J., Patsios, D., Sauerbrei, E., Ellis, P.M., Arnold, A., Goss, G., Leighl, N.B., Shepherd, F.A., Powers, J., Seymour, L. and Laurie, S.A. (2009) Tumor cavitation: impact on objective response evaluation in trials of angiogenesis inhibitors in non-small-cell lung cancer. Journal of Clinical Oncology, 27, (3), 404-410. (doi:10.1200/JCO.2008.16.2545).
Nolan, L., Johnson, P.W.M., Ganesan, A., Packham, G. and Crabb, S.J. (2008) Will histone deacetylase inhibitors require combination with other agents to fulfil their therapeutic potential? British Journal of Cancer, 99, 689-694. (doi:10.1038/sj.bjc.6604557).
Crabb, S.J., Howell, M., Rogers, H., Ishfaq, M., Yurek-George, A., Carey, K., Pickering, B.M., East, P., Mitter, R., Maeda, S., Johnson, P.W.M., Townsend, P., Shin-Ya, K., Yoshida, M., Ganesan, A. and Packham, G. (2008) Characterisation of the in vitro activity of the depsipeptide histone deacetylase inhibitor spiruchostatin. Biochemical Pharmacology, 76, (4), 463-475. (doi:10.1016/j.bcp.2008.06.004). (PMID:18611394).
Crabb, Simon J., Hague, Angela, Johnson, Peter W.M. and Packham, Graham (2008) BAG-1 inhibits PPARgamma-induced cell death, but not PPARgamma-induced transcription, cell cycle arrest or differentiation in breast cancer cells. Oncology Reports, 19, (3), 689-696.
Crabb, S.J., Cheang, M.C., Leung, S, Immonen, T, Nielsen, T.O., Huntsman, D.D., Bajdik, C.D. and Chia, S.K. (2008) Basal breast cancer molecular subtype predicts for lower incidence of axillary lymph node metastases in primary breast cancer. Clinical Breast Cancer, 8, (3), 249-256. (doi:10.3816/CBC.2008.n.028).
Ryan, G., Martinelli, G., Kuper-Hommel, M., Tsang, R., Pruneri, G., Yuen, K., Roos, D., Lennard, A., Devizzi, L., Crabb, S., Hossfeld, D., Pratt, G., Dell'Olio, M., Choo, S.P., Bociek, R.G., Radford, J., Lade, S., Gianni, A.M., Zucca, E., Cavalli, F. and Seymour, J.F. (2008) Primary diffuse large B-cell lymphoma of the breast: prognostic factors and outcomes of a study by the International Extranodal Lymphoma Study Group. Annals of Oncology, 19, (2), 233-241. (doi:10.1093/annonc/mdm471).
Crabb, S.J., Bajdik, C.D., Leung, S., Speers, C.H., Kennecke, H, Huntsman, D.G. and Gelmon, K.A. (2008) Can clinically relevant prognostic subsets of breast cancer patients with four or more involved axillary lymph nodes be identified through immunohistochemical biomarkers? A tissue microarray feasibility study. Breast Cancer Research, 10, (1) (doi:10.1186/bcr1847). (PMID:18194560).
Lee, San San, Crabb, Simon J., Janghra, Nari, Carlber, Carsten, Williams, Ann C., Cutress, Ramsey I., Packham, Graham and Hague, Graham (2007) Subcellular localisation of BAG-1 and its regulation of vitamin D receptor-mediated transactivation and involucrin expression in oral keratinocytes: Implications for oral carcinogenesis. Experimental Cell Research, 313, (15), 3222-3238. (doi:10.1016/j.yexcr.2007.06.010).
Sharp, Adam, Crabb, Simon J., Cutress, Ramsey I., Brimmell, Matthew, Wang, Xiu-hong, Packham, Graham and Townsend, Paul A. (2004) BAG-1 in carcinogenesis. Expert Reviews in Molecular Medicine, 6, (7), 1-15. (doi:10.1017/S1462399404007537). (PMID:15033003).
Crabb, S.J., McKendrick, J.J. and Mead, G.M. (2002) Brain as sanctuary site of relapse in germ cell cancer patients previously treated with chemotherapy. Clinical Oncology, 14, (4), 287-293. (doi:10.1053/clon.2002.0075).
Tate, A R, Crabb, S, Griffiths, J R, Howells, S L, Mazucco, R A, Rodrigues, L M and Watson, D (1996) Lipid metabolite peaks in pattern recognition analysis of tumour in vivo MR spectra. Anticancer research, 16, (3B), 1575-9. (PMID:8694529).

Book Section

Cutress, Ramsay I., Crabb, S.J., Sharp, A., Townsend, P.A. and Packham, G. (2007) The significance and function of BAG-1 in breast cancer. In, Yao, Andrew P. (ed.) New Developments in Breast Cancer Research. USA, Nova Science, 1-30. (Horizons in Cancer Research, 23).
 

Research

Research Interests

Dr Crabb's laboratory and clinical research interests are in the development of new therapeutic options for genitourinary cancers.

Epigenetic Therapeutics

In addition to abnormalities of DNA sequence, complex epigenetic abnormalities are also recognised to underpin cancer development. Epigenetic abnormalities are attractive therapeutic targets as they may potentially be amenable to direct correction through inhibition of their enzymatic mediators. Dr Crabb is interested in the development of therapeutic agents to target epigenetic processes in cancer. Previous work has involved investigation of novel histone deacetylase (HDAC) inhibitors and the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in prostate, breast and bladder cancers. Current work is looking at the histone demethylase LSD1. Work is currently ongoing to develop chemical inhibition of this enzyme which mediates androgen receptor function as a novel therapeutic strategy for prostate cancer.

Mechanisms of Chemotherapy Resistance

The group is investigating mechanisms for the development of chemotherapy resistance in bladder and other cancers. The transcription factor Nrf2 controls expression of multiple target genes, each containing an antioxidant response element. These targets mediate cellular protection through antioxidant response, cellular detoxification (including glutathione conjugation) and altered drug uptake/efflux. Some Nrf2 targets (e.g. metallothionein, glutathione reductase) are associated with bladder cancer characteristics, outcomes and chemotherapy resistance. Nrf2 regulation is partially understood and includes negative regulation by Keap1 and phosphorylation. De-novo or acquired cisplatin resistance is a problem in bladder cancer. Ongoing work is testing the hypothesis that Nrf2 is a mediator in part of cisplatin resistance in bladder cancer and potential means to reverse it therapeutically that might then be amenable to clinical testing.

Molecularly Targeted Therapeutic Strategies for Bladder Cancer

Dr Crabb's work is looking at the potential to target the human epidermal growth factor receptor (HER) family in bladder cancer. The HER family are cell surface tyrosine kinase receptors which include the epidermal growth factor receptor (EGFR, HER1), HER2, HER3 and HER4. Aberrant HER family activation of downstream signalling pathways results in multiple biological effects in cancer cells including increased cellular proliferation, migration, attenuation of apoptosis, invasion and metastasis. Both EGFR and HER2 are over-expressed in a proportion of bladder cancers and relationships have been demonstrated between increased expression and tumour grade, tumour stage and survival outcomes. Drugs targeting EGFR and/or HER2 are in clinical trials for bladder cancer. The group's interests are in understanding the degree to which co-inhibition of these receptors and downstream pathways will be required for them to be used as a therapeutic strategy in this disease and in the elucidation of resistance mechanisms to such strategies.

Clinical Trials

Dr Crabb leads an active clinical trials portfolio in bladder and prostate cancers in Southampton and is actively involved in the leadership of national early phase studies in these diseases. He is chief investigator for the ProCAID trial in prostate cancer.

Academic unit:  Cancer Sciences

Responsibilities

Post Doctoral Supervision

Current

Dr Sergio Regufe da Mota

Previous

Dr Sarah Bailey
Dr Annette Hayden

Doctoral Student Supervision

Current

Regina Mora Vidal
James Douglas

National Responsibilities

British Association for Cancer Research Executive Committee member
NCRI Bladder Cancer Clinical Studies Group member
NCRI Prostate Cancer Clinical Studies Group member
Chemotherapy Subgroup member of the NCRI Bladder Cancer Clinical Studies Group
Advanced Prostate Cancer Subgroup member of the NCRI Prostate Cancer Clinical Studies Group

Teaching Responsibilities

BM5 and BM4. Provides clinical teaching to all years, based at Southampton General Hospital

Head of Field for Oncology for BMedSc projects.

Contact

Dr Simon Crabb
Somers Cancer Research Building
Southampton General Hospital
Mailpoint 824
Tremona Road
Southampton
SO16 6YD

Room Number: SGH/CSB/MP824

Telephone: (023) 8120 5170
Facsimile: (023) 8120 5152
Email: S.J.Crabb@southampton.ac.uk