Staff Profile | Faculty of Medical Sciences (2024)

Professor Nicola Curtin

Professor of Experimental Therapeutics

  • Email: nicola.curtin@ncl.ac.uk
  • Telephone: +44 (0) 191 208 4415
  • Fax: +44 (0) 191 208 4301
  • Address: Newcastle University
    Translational and Clinical Research Institute
    Newcastle University Centre for Cancer
    Faculty of Medical Sciences
    Paul O'Gorman Building
    Newcastle upon Tyne
    NE2 4HH

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 seehttps://en.wikipedia.org/wiki/Nicola_Curtin

ROLES AND RESPONSIBILITIES

Team Leader: DNA damage response

Member of FMS Equality, Diversity and Inclusion Team

Former member of both Senate and Council (2015-2020)

Chair NCRI CTRad Workstream 1

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.

1990-6Senior 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)

Yorkshire Cancer Research Scientific Advisory Board

Science Foundation Ireland Scientific Advisory Board

Research Council of Norway Strategic Initiative on Cancer Research: Panel member

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

Leukaemia and Lymphoma Research (site visit panel)

CRUK-EORTC committee on NCI compounds

Research

RESEARCH INTERESTS

My work focusses primarily on how DNA damage is signalled to cell cyclecheckpoints and DNA repair, otherwise known as the DNA damage response (DDR),and how this can be used for improved cancer therapy. The most exciting discovery from my lab was the synthetic lethality of PARP inhibitors (PARPi) in cancers lacking hom*ologous recombination DNA repair (HRR), e.g. due to BRCA mutations. This discovery, published in 2005 in Nature has led to a major paradigm shift in the treatment of cancers and now 4 PARPi (including rucaparib, that I helped to develop from 1997 to 2010) are approved for cancer therapy.

Current Work

1. The evaluation of drugs targeting DDR pathways: PARP, DNA-PK, ATM, ATR CHK1, Wee1

  • 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 signalsand promotes the repair of DNA double strand breaks that are highly cytotoxic and ATM/CHK2 and ATR/CHK1/Wee1 signalDNA damage to cell cycle checkpoints so cells don’t try to replicate withdamaged DNA.
  • PARP inhibitors

2. The identification and therapeutic exploitation of the dysregulation ofthe DNA damage response, which is a common characteristic of cancer. Inparticular, identifying determinants of sensitivity to drugs that target componentsof the DNA damage response, like PARP and ATR inhibitors that may subsequentlybe used to develop predictive biomarkers to stratify patients to appropriatetherapy.

  • The development of anassay for hom*ologous recombination DNA repair (HRR) function that can be usedon patients’ tumour cells. HRR defects are largely tumour-specific and adeterminant of sensitivity to PARP inhibitors so this allow patientstratification for PARP inhibitor therapy
  • Identification that commoncancer-associated defects in the DNA damage response make cells more sensitiveto killing with ATR inhibitors.

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

Other Expertise

Antifolates, cancer metabolism, nucleosidetransport

Postgraduate supervision

PhD students: 22 completed on time, 2 awarded the faculty prize, 3ongoing

MD students: 4 completed on time, 1 ongoing

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

Esteem Indicators

REFimpact case 2014

Prize:CR UK Translational Research Prize Nov 2010

Committee membership

Yorkshire Cancer Research Scientific AdvisoryBoard

NCRI Clinical and TranslationalRadiotherapy Research Working Group (CTRad)

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

Science Foundation Ireland ScientificAdvisory Board (occasional)

Leukaemia and Lymphoma Research (sitevisit panel)

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

Editorial Board

Expert Reviews in Molecular Medicine - Editor in Chief

British Journal of Pharmacology

Cancers

AmericanJournal 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 ReviewsCancer, Nature Reviews Drug Discovery, Lancet Oncology

Funding (current)

Intermittent PARP inhibitor in recurrent ovarian cancer (IPIROC). A Mukhopadhyay and NJ Curtin (Co PI) £30,000 seedcorn funding CRUK DBT/ Wellcome Trust India Alliance Affordable Approaches to Cancer

Investigating therapeutic application of PARP inhibitor as chemo-radiosensitser in cervical cancer and its effect on renal protection. NJ Curtin (PI) Academy of Medical Sciences £99,000 (2019-2021)

Increasing the therapeutic application of PARP inhibitors in ovarian cancer by inhibiting DNA repair. NJ Curtin (PI), R O’Donnell, Y Drew, A Mukhopadhyay. JGWP £49,950 (2017-2018)

Systems Medicine of Metabolic Signalling Networks: A New Concept for Breast Cancer Stratification. (K. Thedieck Co-ordinator, Groningen, Netherlands) Horizon 2020 £258,700

Investigation of the effects of DNA repair inhibitors in pre-clinical models of neuroblastomas with ATM, MYCN and TP53 abnormalities. D Tweddle and NJ Curtin co-applicants Little Princess Trust £100,000 (01/09/2017-31/08/2020)

NEOCATS – Northern nEoadjuvant Ovarian CAncer Translational Study. Y Drew, R O’Donnell and NJ Curtin Newcastle Healthcare Charity £289,163 01/03/2018-29/02/2020

Investigating BRCAness in epithelial ovarian cancer (EOC) in India to develop stratified surgical and chemotherapy options. NJ Curtin (UK PI) A Mukhopadhyay (India PI) DST-UKIERI (British Council) £78,470 April 2017-March 2021

Understanding synthetic lethality of ATR inhibitors with DDR dysregulation common in ovarian cancer. NJ Curtin (PI) Y Drew, F Zenke (Merck) £141,636 MRC Industrial CASE 1/10/2016- 25/12/2020

Funding (Previous)

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

Patents

1.Griffin, R. J., Calvert,A. H., Curtin, N. J., Newell, D. R.,and Golding, B. T. Benzamide AnaloguesADPRT (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 PARPInhibitors.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.PatentApplication Number PCT/GB97/02701.5

4.Griffin, R. J., Calvert, A. H., Curtin, N. J., Newell, D. R. and Golding, B. T. PyrimidopyrimidineCompounds. Patent Application NumberPCT/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. PatentApplication 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. PatentApplication 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 PatentApplication 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. PatentApplication 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. PatentApplication 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-PKinhibitors. Patent Application Number PCT/GB2002/003740

13.Helleday T and Curtin NJ. Therapeutic Compounds (PARP inhibitors in hom*ologousrepair/BRCA defective cancer) Patent Application Number PCT/GB2004/003183.Publication number WO 2005/012305 A2 Divisional application 16th April 2004 GB0408524.7

14.Newcastle Inventors. Calvert AH, Curtin NJ, Jones C, Newell DR, PlummerER and Thomas HR. TherapeuticCombinations Comprising PARP inhibitor US application No. 60/612,458 Filed 22ndSeptember 2004 WO/2006/033006)THERAPEUTIC COMBINATIONS COMPRISING POLY(ADP-RIBOSE) POLYMERASES INHIBITOR

15.Falcon S, Reaper P, PollardJ, Curtin NJ, Middleton FK and ChenT. Method for measuring ATR inhibition mediated increases in DNA damage. USpatent application#14/045,373

Industrial Relevance

Much of my work has been in collaboration withPharmaceutical companies and has been financially supported by: AgouronPharmaceuticals, Astra Zeneca, BioMarin, BiPar Sciences, Clovis, Cyclacell, EliLilley, KuDOS, Merck, Pfizer, and Vertex Pharmaceuticals. I consult for: Abbot,BioMarin, Eisai, Tesaro

Teaching

Undergraduate Teaching

Personal Tutor

Supervisor of final year projects and Erasmus Students

Lecture on PED306

Postgraduate Teaching

MSc Oncology and Palliative Care Module leader: Pharmacology ofAnticancer Drugs

MRes Project supervisor

Publications

Staff Profile | Faculty of Medical Sciences (2024)

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