Faculty of Medical Sciences

Staff Profile

Professor Nicola Curtin

Professor

Background

Introduction

Professor of Experimental Cancer Therapeutics, since 2006, having worked in Newcastle since 1982. More than 30 years’ experience in the development and biological evaluation of novel drugs to treat cancer and the development of biomarkers to predict and assess their effects. Major interest is in targeting the DNA damage response see http://www.ncl.ac.uk/impact/Cancer-research-smart-drugs.php

ROLES AND RESPONSIBILITIES

Team Leader: DNA damage response

Module leader: Cancer Pharmacology module online MSc Oncology

Chair: Athena SWAN self-assessment team

 

QUALIFICATIONS

BA (Biology) University of York 1975

MSc Liver carcinogenesis Manchester University 1977

PhD Biochemistry of liver carcinogenesis University of Surrey 1981

PREVIOUS POSITIONS

2002-6           Senior Lecturer in Cell Biology and Experimental Therapeutics of Cancer, Northern Institute for Cancer Research, University of Newcastle upon Tyne.

1996-2002 Lecturer in Cell Biology and Experimental Therapeutics of Cancer, Cancer Research Unit, University of Newcastle upon Tyne.

1990-1996                 Senior Research Associate, Cancer Research Unit, University of Newcastle upon Tyne.

1985-1990    Research Associate, Cancer Research Unit. University of Newcastle upon Tyne.

1982-1985    Research Associate, Public Health Laboratories, Newcastle upon Tyne.

 

MEMBERSHIPS

British Association Cancer Research

American Association Cancer Research

NCRI Clinical and Translational Radiotherapy Research Working Group (CTRad)

Research

RESEARCH INTERESTS

My work focusses primarily on how DNA damage is signalled to cell cycle checkpoints and DNA repair, otherwise known as the DNA damage response (DDR), and how this can be used for improved cancer therapy.

Current Work

1.       The evaluation of drugs targeting DDR pathways: PARP, DNA-PK, ATM and ATR.

  • PARP signals and promotes the repair of DNA breaks (mostly single-stranded) that are the most common form of naturally occurring DNA damage. DNA-PK signals and promotes the repair of DNA double strand breaks that and ATM and ATR signal DNA damage to cell cycle checkpoints so cells don’t try to replicate with damaged DNA.

2.      The identification and therapeutic exploitation of the dysregulation of the DNA damage response, which is a common characteristic of cancer. In particular, identifying determinants of sensitivity to drugs that target components of the DNA damage response, like PARP and ATR inhibitors that may subsequently be used to develop predictive biomarkers to stratify patients to appropriate therapy.

  • The development of an assay for homologous recombination DNA repair (HRR) function that can be used on patients’ tumour cells. HRR defects are largely tumour-specific and a determinant of sensitivity to PARP inhibitors so this allow patient stratification for PARP inhibitor therapy
  •   Identification that common cancer-associated defects in the DNA damage response make cells more sensitive to killing with ATR inhibitors.

3.      The development of pharmacodynamic biomarkers to monitor the activity of novel drugs targeting the DNA damage response (published assays are for PARP and ATR inhibitors) that can be used in clinical trials.

Other Expertise

Antifolates, cancer metabolism, nucleoside transport

Postgraduate supervision

PhD students: 17 completed on time, 2 awarded the faculty prize, 2 ongoing

MD students: 2 completed on time, 1 ongoing

MSc Oncology (web-based learning) : Module leader of Cancer Pharmacology module

Esteem Indicators

REF impact case 2014

Prize: CR UK Translational Research Prize Nov 2010

Committee membership

Yorkshire Cancer Research Scientific Advisory Board

NCRI Clinical and Translational Radiotherapy Research Working Group (CTRad)

Council of Life Sciences of OTKA (Hungarian Scientific Research Fund, annually)

Science Foundation Ireland Scientific Advisory Board (occasional)

Leukaemia and Lymphoma Research (site visit panel)

Research Council of Norway Strategic Initiative on Cancer Research: Panel member (approx. biannually)

Editorial Board

Anti-Cancer Drugs

British Journal of Pharmacology

Expert Reviews in Molecular Medicine

American Journal of Translational Research

Other

Regular reviewer of grants proposals submitted to CRUK, MRC, Wellcome

Regular reviewer of manuscripts submitted to, Nature, Nature Medicine, Nature Reviews Cancer, Cancer Research, Clinical Cancer Research, Molecular Cancer Therapeutics, Oncogene, Oncotarget

Invited Reviews: Nature Reviews Cancer, Lancet Oncology

 

Funding (current)

CR UK: Preclinical combination studies if imatinib and olaparib in Homologous recombination stratified relapsed ovarian cancer £49,825

JGW Patterson Foundation: Do sex and organ-specific differences in PARP and SIRT1 contribute to cancer? £49,987.28

Northern Cancer Care & Research Society: Investigation of the role of HPV DNA and PARP expression in cervical cancer. £32,000

JGW Patterson Foundation: Improving the response rate in ovarian cancer by compromising DNA repair £49,958

Newcastle Health Care Charity: Determination of Homologous Recombination Repair (HRR) function in malignant ascites: optimisation and validation for multicentre stratified medicine trials £49,896.78.

Cyclacell: Therapeutic Potential of Sapacitabine in Cancers Defective in Homologous Recombination. £32,000

Funding (Previous)

Grant income for previous 10 years as PI £1,981,200 from Industry, £587,500 from Cancer Charities and £68,000 from Research Councils. Co. I. £10 million from Charities and £211,000 from Industry

Patents
  1. Griffin, R. J., Calvert, A. H., Curtin, N. J., Newell, D. R., and Golding, B. T.  Benzamide Analogues ADPRT (PARP) Inhibitors. Patent Application Number PCT/GB95/00513 (1995)
  2. Griffin, R. J., Calvert, A. H., Curtin, N. J., Newell, D. R. and Golding, B. T. Benzimidazole PARP Inhibitors.Patent Application Number PCT/GB96/01832.
  3. Griffin, R. J., Calvert, A. H., Curtin, N. J., Newell, D. R. and Golding, B. T.  Prodrugs of PARP Inhibitors.Patent Application Number PCT/GB97/02701.5
  4. Griffin, R. J., Calvert, A. H., Curtin, N. J., Newell, D. R. and Golding, B. T. Pyrimidopyrimidine Compounds.  Patent Application Number PCT/GB97/06618.7.
  5. Griffin, R. J., Calvert, A. H., Curtin, N. J., Newell, D. R. and Golding, B. T., Endicott, J.A., Noble, M.E.M., Boyle, F.T. and Jewsbury, P.J. Purine CDK Inhibitors. Patent Application Number PCT/GB97/14603.9
  6. Griffin, R. J., Calvert, A. H., Curtin, N. J., Newell, D. R. and Golding, B. T. Endicott, J.A., Noble, M.E.M., Boyle, F.T. and Jewsbury, P.J. Pyrimidine CDK Inhibitors. Patent Application Number PCT/GB98/06739.0
  7. Griffin, R. J., Calvert, A. H., Curtin, N. J., Newell, D. R. and Golding, B. T. Dipyridamole analogues. Patent Application Number PCT/GB98/00966
  8. Griffin, R. J., Calvert, A. H., Curtin, N. J., Newell, D. R. Golding, B. T., Hardcastle I, Endicott, J.A., Noble, M.E.M., Boyle, F.T. and Jewsbury, P.J. Anilinopurine CDK Inhibitors. Patent Application Number PCT/GB01/01686.4
  9. Griffin, R. J., Calvert, A. H., Curtin, N. J., Newell, D. R., Golding, B. T. Hardcastle, I.R., Martin, N., Smith, G.C.M., Raynaud, F. and Workman, P. DNA-PK inhibitors – 1 Patent Application Number PCT/GB01/19865.4 GB/14.08.01/GBA0119865.4
  10. Griffin, R. J., Calvert, A. H., Curtin, N. J., Newell, D. R., Golding, B. T. Hardcastle, I.R., Martin, N., Smith, G.C.M., Raynaud, F. and Workman, P. DNA-PK inhibitors-2. Patent Application Number PCT/GB01/19863.9
  11. Griffin, R. J., Calvert, A. H., Curtin, N. J., Newell, D. R., Golding, B. T. Hardcastle, I.R., Martin, N., Smith, G.C.M., Raynaud, F. and Workman, P. DNA-PK inhibitors-3. Patent Application Number 04014411.4
  12. Griffin, R. J., Calvert, A. H., Curtin, N. J., Newell, D. R., Golding, B. T. Hardcastle, I.R., Martin, N., Smith, G.C.M., Raynaud, F. and Workman, P. Thiopyran-4-ones as DNA-PK inhibitors. Patent Application Number PCT/GB2002/003740
  13. Helleday T and Curtin NJ. Therapeutic Compounds (PARP inhibitors in homologous repair/BRCA defective cancer) Patent Application Number PCT/GB2004/003183. Publication number WO 2005/012305 A2 Divisional application 16th April 2004 GB 0408524.7
  14. Newcastle Inventors. Calvert AH, Curtin NJ, Jones C, Newell DR, Plummer ER and Thomas HR.  Therapeutic Combinations Comprising PARP inhibitor US application No. 60/612,458 Filed 22nd September 2004 WO/2006/033006) THERAPEUTIC COMBINATIONS COMPRISING POLY(ADP-RIBOSE) POLYMERASES INHIBITOR
  15. Falcon S, Reaper P, Pollard J, Curtin NJ, Middleton FK and Chen T. Method for measuring ATR inhibition mediated increases in DNA damage. US patent application#14/045,373

 

Industrial Relevance

Much of my work has been in collaboration with Pharmaceutical companies and has been financially supported by: Agouron Pharmaceuticals, Astra Zeneca, BioMarin, BiPar Sciences, Clovis, Cyclacell, Eli Lilley, KuDOS, Pfizer, and Vertex Pharmaceuticals. I consult for: Abbot, BioMarin, Eisai, Tesaro

 

Teaching

Undergraduate Teaching

Supervision of final year project students

Postgraduate Teaching

Supervisor of PhD students
Module leader on web-based MSc in Oncology
Project supervisor for MRes students from Newcastle and York
Exchange programme for students at the University of Konstanz

Publications