BSc, MBBS, MRCP, PhD
- Primary position:
- Senior Lecturer in Medical Oncology
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.
BSc, Biochemistry, University of London, 1993
MBBS, Medicine, University of London, 1996
MRCP, Royal College of Physicians, 2000
PhD, University of Southampton, 2006
Senior Lecturer in Medical Oncology, University of Southampton Faculty of Medicine
Honorary Consultant in Medical Oncology, University Hospital Southampton NHS Foundation Trust
The University of Southampton's electronic library (e-prints)
Dr Crabb's laboratory and clinical research interests are in the development of new therapeutic options for genitourinary cancers.
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.
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
Post Doctoral Supervision
Dr Sergio Regufe da Mota
Dr Sarah Bailey
Dr Annette Hayden
Doctoral Student Supervision
Regina Mora Vidal
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
BM5 and BM4. Provides clinical teaching to all years, based at Southampton General Hospital
Head of Field for Oncology for BMedSc projects.