Dr Prabhakar Rajan

Dr Prabhakar Rajan

MA PhD FRCS(Urol)
Centre: Centre for Molecular Oncology
Clinical Senior Lecturer in Urology
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My laboratory research examines the role of and functions of RNA-binding proteins (RBPs) and alternative pre-mRNA splicing in prostate cancer (PCa) biology, using a combination of pre-clinical cancer models and next generation sequencing-based techniques.

We are actively involved in translational research, investigating RBP expression in primary PCa, as well as transcriptomic changes during PCa treatment with chemo- and endocrine therapies.

Our clinical research explores the epidemiological aspects of treatments for PCa.

Research Details

Treatment-resistant metastasis is the predominant cause of prostate cancer (PCa)-related death. Our laboratory-based research programme at Barts Cancer Institute explores how post-transcriptional mechanisms of gene regulation underlie both the metastatic and treatment-resistant PCa phenotypes.

A major focus in our group is the role of a ubiquitous genetic process, termed alternative pre-mRNA splicing, where coding (exons) and non-coding (introns) regions of a gene are shuffled to create structurally/functionally different protein isoforms. Alternative splicing is controlled by trans-acting RNA-binding proteins (RBPs), which bind cis-elements within the nascent pre-mRNA. RBPs also have key roles in other aspects of RNA processing and metabolism.

We are exploring the expression and localization of RBPs in primary prostate tumours. We are interested in the contribution of RBPs to the differential regulation of the transcriptome and proteome in metastatic and treatment resistant phenotypes using “omics” technologies (iCLIP, RNA-Seq, SILAC) and genetic screens (CRISPR, RNAi).

We anticipate that our programme will:

  1. reveal the phenotype of RBP-driven metastasis and treatment-resistant PCa;
  2. enumerate RBP target mRNA targets in PCa cells;
  3. reveal qualitative and quantitative changes in the PCa transcriptome and proteome regulated by RBPs.

Ultimately, we hope to identify clinically-relevant and potentially actionable events that will help to delineate novel therapeutic strategies for metastatic and treatment-resistant PCa.

Profile

Key Qualifications

  • 2008 PhD (Prostate Cancer Biology), Newcastle University
  • 2012 FRCS(Urol.), Royal College of Surgeons of England

Recent Appointments

  • 2008-2014 West of Scotland Training Programme in Urology
  • 2008-2013 Clinical Lecturer in Urology, University of Glasgow
  • 2013-2015 Clinical Research Fellow, University of Glasgow
  • 2015-to date Consultant Urologist, Barts Health and University College London Hospitals NHS Trusts
  • 2015-to date Clinical Senior Lecturer in Urology, Queen Mary University of London

Funding

  • 2015 - 2017: The Prostate Cancer Foundation - Project Grant: “OptiChem: Optimizing the use of taxane chemotherapy in prostate cancer” (Co-applicant), ~£ 550,000
  • 2014 - 2017: Prostate Cancer UK - PhD Studentship: “Characterisation of mRNA isoforms as potential clinical biomarkers and molecular drivers of prostate cancer”(Co-applicant), £ 92,663
  • 2013 - 2016: Prostate Cancer UK - Project Grant: “Identifying novel mechanisms of androgen-mediated growth control as new targets for intervention and prognostic biomarkers in prostate cancer”  (Co-applicant), £ 159,129
  • 2013 - 2019: Royal College of Surgeons of England/Cancer Research UK - Clinician Scientist Fellowship in Surgery “Analysis of alternative splicing in prostate cancer metastasis regulated by the RNA-binding proteins Sam68 and hnRNP A2/B1”  (Principal Investigator), >£800,000

Key Publications

The RNA-binding protein Sam68 regulates expression and transcription function of the androgen receptor splice variant AR-V7. Stockley J, Markert E, Zhou Y, Robson CN, Elliott DJ, Lindberg J, Leung HY*, Rajan P*. Sci Rep. 2015; 5:13426 PMID: 26310125 *Equal contributors

The RNA-binding protein hnRNPA2 regulates β-catenin protein expression and is over-expressed in prostate cancer. Stockley J, Villasevil MEM, Nixon C, Ahmad I, Leung HY*, Rajan P*. RNA Biol. 2014; 11(6) PMID: 24823909*Equal contributors

Next-generation Sequencing of Advanced Prostate Cancer Treated with Androgen-deprivation Therapy. Rajan P*, Sudbery IM*, M. Eugenia M. Villasevil MEM, Mui E, Fleming J, Davis M, Ahmad I, Edwards J, Sansom OJ, Sims D, Ponting CP, Heger A, McMenemin RM, Pedley ID, Leung HY. Eur Urol. 2014; 66(1):32-9 PMID: 24054872 *Equal contributors

The RNA-binding and adaptor protein Sam68 modulates signal-dependent splicing and transcriptional activity of the androgen receptor. Rajan P*, Gaughan L*, Dalgliesh C, El-Sherif A, Robson CN, Leung HY, Elliott DJ. J Pathol. 2008; 215(1):67-77 PMID: 18273831 *Equal contributors

 


Further Publications

For additional publications, please click here


My laboratory research examines the role of and functions of RNA-binding proteins (RBPs) and alternative pre-mRNA splicing in prostate cancer (PCa) biology, using a combination of pre-clinical cancer models and next generation sequencing-based techniques.

We are actively involved in translational research, investigating RBP expression in primary PCa, as well as transcriptomic changes during PCa treatment with chemo- and endocrine therapies.

Our clinical research explores the epidemiological aspects of treatments for PCa.

External Activities

  • 2015 - Executive Committee – British Association of Urological Surgeons Section of Academic Urology
  • 2016 - Research Fellowship and Lectureship Group – Royal College of Surgeons of England

See other researchers working on:

Genitourinary Cancer Metastasis and Invasion Prostate
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