Ricky Sharma MA MRCP FRCR Ph.D.

DNA Adduct Repair Group
Translation of biochemical knowledge of DNA adducts and excision repair to the prevention and treatment of cancer.

Dr. Ricky Sharma

Email 
Tel  +44 (0)1865 235209
Contact address  Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Headington, Oxford OX3 7DQ
Department  Department of Oncology
College Harris Manchester College

Research Summary

Adducts arise from the covalent modification of nucleosides in DNA. The existence of specific DNA repair pathways that have evolved to remove adducts formed by endogenous mutagens and exogenous toxins may be considered strong evidence in favour of their relevance to evolution and cancer biology.

The aim of the DNA Adduct Repair Group is to characterise fundamental biological mechanisms involved in the repair of adducts formed by reactive oxygen species, radiotherapy and platinum chemotherapies.  The ultimate goal of this research programme is to translate biochemical knowledge of adduct formation and repair into clinical studies of cancer prevention and treatment.

The group is currently focussed on the effects of platinum chemotherapies on DNA.  These laboratory studies are ongoing in parallel with Dr Sharma’s clinical studies of oxaliplatin as a radiosensitiser in the treatment of liver metastases from colorectal cancer.  In collaboration with Dr Grigory Dianov’s group, cellular pathways of excision repair are being characterised in preclinical models as potential targets for improving current cancer therapies.

The research programme is funded by the NIHR Biomedical Research Centre Oxford, Cancer Research UK, the UK Medical Research Council via the Daphne Jackson Trust, the Bobby Moore Fund of Cancer Research UK, Sirtex Medical Ltd. and the Higher Education Funding Council for England.

The FOXFIRE trial is now open for recruitment to find out more please click this link: FOXFIRE Newsletter

Dr. Sharma was appointed as Clinical Lead for the Thames Valley Cancer Research Network http://www.tvcn.nhs.uk/research/ in May 2010.  TVCRN is part of the National Cancer Research Network (NCRN), which is part of the National Institute for Health Research (NIHR).  Dr. Sharma's aim in this post is to improve the speed, quality and integration of research in the Thames Valley, ultimately resulting in improved care for patients with cancer in Berkshire, Buckinghamshire, Oxfordshire and Swindon.

Collaborators

Group Members

  • Dr Rebecca Carter, Daphne Jackson Trust Fellow
  • Dr Thomas MacGregor, Clinical Research Fellow
  • Azadeh Cheraghchi-Bashi-Astaneh, Research Assistant
  • Nigar Syed, Researcher

Collaborators

    Biography

    Dr Ricky Sharma is the Laboratory Group Leader of the Translational DNA Repair Group at the CRUK/MRC Oxford Institute for Radiation Oncology within the Department of Oncology at the University of Oxford. He is also a Higher Education Funding Council for England (HEFCE) Clinical Senior Lecturer at the University of Oxford, an Honorary Consultant in Clinical Oncology at the Oxford University Hospitals NHS Trust, and a Senior Research Fellow at Harris Manchester College, University of Oxford.

    Dr Sharma completed his medical training at the University of Cambridge, after which he undertook a research fellowship at the MRC Toxicology Unit at the University of Leicester leading to the award of Doctor of Philosophy. He trained in both Medical and Clinical Oncology at the University Hospitals of Leicester and the Royal Marsden Hospital, London.  Dr Sharma is a Fellow of both the Royal College of Physicians and the Royal College of Radiologists.

    Dr Sharma has a prominent national and international profile in his field.  Dr Sharma co-chairs the Early Phase Trials Workstream of the NCRI Clinical Translational Radiotherapy (CTRad) Group and is the Chief Investigator of the NCRN FOXFIRE, a multi-centre, clinical randomised clinical trial testing a new combination of chemotherapy and selective internal radiotherapy in the treatment of liver metastases from colorectal cancer.  He is an examiner for Royal College of Radiologists (Clinical Oncology) a member of Faculty Board and a prominent member of several working groups within the college, particularly on interventional oncology and undergraduate education.  in addition to being a tutor at Harris Manchester College and St Catherine's College, University of Oxford, Dr Sharma is a module leader for postgraduate teaching of radiobiology and oncology and is leading the development of a national mentorship scheme for clinical oncology trainees.  He was appointed as Chair of the Teaching Committee of the Department of Oncology at the University of Oxford in May 2011.

    Current Appointments

    2009 HEFCE Clinical Senior Lecturer, University of Oxford

    2006 - 2009  Senior Fellow, University of Oxford

    2007 - Honorary Consultant in Clinical Oncology, Oxford Radcliffe Hospitals

    Previous Appointments

    2004 – 2006    Senior Registrar, Royal Marsden Hospital, London

    2001 – 2006    Honorary Lecturer, University of Leicester

    1998 – 2001    Clinical Research Fellow and Honorary Registrar, MRC Toxicology Unit and University Hospitals of Leicester

    Degrees and Qualifications

    2005  Fellow, Royal College of Radiologists

    2001  Doctor of Philosophy, University of Leicester

    1998  Member, Royal College of Physicians

    1996  Master of Arts, University of Cambridge

    1994  Bachelor of Medicine and Chirurgia, University of Cambridge

    1992  Bachelor of Arts, University of Cambridge

    Publications

    Selected Publications:

    Helleday T, Petermann E, Lundin C, Hodgson B, and Sharma RA (2008). DNA repair pathways as targets for cancer therapy. Nature Rev Cancer, 8: 193-204.

    Parsons JL, Tait PS, Finch D, Dianova IL, Edelmann MJ, Khoronenkova SV, Kessler BM, Sharma RA, McKenna WG, Dianov GL (2009).  Ubiquitin ligase ARF-BP1/Mule modulates base excision repair.  EMBO J, 28: 3207-3215.

    Nicolay NH, Berry DP, Sharma RA (2009).  Liver metastases from colorectal cancer: role of radio-embolization with systemic therapy.  Nature Rev Clin Oncol, 6: 687-697.

    Yang J, Parsons J, Nicolay NH, Caporali S, Harrington CF, Singh R, Finch D, D’Atri S, Farmer PB, Johnston PG, McKenna WG, Dianov G, Sharma RA (2010).  Cells deficient in the base excision repair protein, DNA polymerase beta, are hypersensitive to oxaliplatin chemotherapy.  Oncogene, 29: 463-468.

    Gottipati P, Vischioni B, Schultz N, Solomons J, Bryant HE, Djureinovic T, Issaeva N, Sleeth K, Sharma RA, Helleday T (2010).  Poly(ADP-ribose) polymerase is hyperactivated in homologous recombination-defective cells.  Cancer Res, 70: 5389-5398.

    Issaeva N, Thomas HD, Djureinovic T, Jaspers JE, Stoimenov I, Kyle S, Pedley N, Gottipati P, Zur R, Sleeth K, Chatzakos V, Mulligan EA, Lundin C, Gubanova E, Kersbergen A, Harris AL, Sharma RA, Rottenberg S, Curtin NJ, Helleday T (2010).  6-thioguanine selectively kills BRCA-2 defective tumors and overcomes PARP inhibitor resistance.  Cancer Res, 50: 6268-6276.

    Nicolay NH, Carter R, Hatch SB, Prevo R, McKenna WG, Helleday T, Sharma RA (2012).  Homologous recombination mediates S-phase dependent radioresistance in cells deficient in DNA polymerase eta.   Carcinogenesis, 33: 2026-34.

    dos Anjos G, Peeters M, Wyatt JC, Sharma RA (2012).  Will the medical student in the team please stand up? Lancet Oncol; 13: 757-758

    Hatch SB, Swift LP, Caporali S, Carter R, Hill EJ, Macgregor TP, D'Atri S, Middleton MR, McHugh PJ, Sharma RA (2013).  XPF protein levels determine sensitivity of malignant melanoma cells to oxaliplatin chemotherapy: Suitability as a biomarker for patient selection.  Int J Cancer. Epub ahead of print

    Sharma RA, Anthony S, Anderson EM (2013).  Clinical benefit and potential pitfalls in combining thermal ablation and radiation therapy to treat liver metastases.  J Clin Oncol. 31: e404-6.