Dr Elaine Willmore
Senior Research Associate

  • Email: elaine.willmore@ncl.ac.uk
  • Telephone: +44 (0) 191 208 4447
  • Fax: +44 (0) 191 208 4301
  • Address: Northern Institute for Cancer Research
    University of Newcastle upon Tyne
    Medical School
    Newcastle upon Tyne
    NE2 4HH

Roles and Responsibilities

Institute Biological Safety Officer


Bsc (hons) Manchester, 1985
PhD Newcastle, 1994

Previous Positions

1999-2004 Senior Research Associate, Institute of Cell & Molecular Biosciences, University of Newcastle-upon-Tyne
1993-1999 Research Associate, School of Biochemistry & Genetics, University of Newcastle upon Tyne.


American Association for Cancer Research
British Association for Cancer Research
British Society for Haematology
UK CLL Forum (Executive Committee)

Honours and Awards

Leukaemia Research Fund Shalit Travel Fellowship (£2,000) to work as a visiting scientist in the laboratory of Prof W. Plunkett, MD Anderson Cancer Center, Texas.

Research Interests

Development of novel therapeutics for Chronic Lymphocytic leukaemia 

DNA Repair enzymes as targets for therapeutic intervention in chronic lymphocytic leukaemia and other tumour types

Targeting of DNA Topoisomerase II by chemotherapeutic agents

Other Expertise

Analysing DNA Topoisomerase targeting using immunofluorescence.
Investigating novel experimental therapeutic strategies using ex-vivo primary leukaemia cells.
DNA repair pathways and associated methods for quantitative analysis

Current Work

Our group focuses on the role of the DNA repair enzymes, DNA-dependent protein kinase (DNA-PK) and ataxia telangiectasia-mutated kinase (ATM) as targets for therapeutic intervention in B-cell chronic lymphocytic leukaemia (CLL).
In collaboration with AstraZeneca we are developing novel, potent and specific inhibitors of DNA-PK and ATM to sensitise cells to clinically used DNA damaging agents. The study builds upon our previous observations that demonstrated sensitisation of leukaemia cell lines to DNA Topoisomerase II-targeting agents by a DNA-PK inhibitor (Willmore et al, Blood 2004).
CLL is a common haematological malignancy and although patients initially respond to the current therapies (e.g. fludarabine, cyclophosphamide, rituximab), many eventually become resistant. Mechanisms of drug-resistance include alterations in the downstream pathways that control DNA double strand break repair, including defects in ATM and over-expression of DNA-PK. In our long-standing collaboration with AstraZeneca, we are developing clinical candidate small molecule inhibitors of DNA-PK that retain potency and specificity and are suitable for phase I clinical trials. We hypothesised that inhibition of one or more DNA double strand break repair pathways will sensitize cells to the effects of the therapeutic DNA damaging agents that are used to treat CLL. A translational study with 3 clinical centres (Newcastle Freeman Hospital, Gateshead QE Hospital & Sunderland Royal Hospital) is ongoing.
We have demonstrated that B-CLL cells (purified from patients) are sensitised to Fludarabine and Chlorambucil by DNA-PK inhibition, and that the mechanism of this sensitisation is increased DNA damage due to inhibition of DNA-PK activation. Furthermore, we made the novel observation that DNA-PK over expression is associated with poor prognosis CLL and shorter overall survival (Willmore et al, Clinical Cancer Research, 2008). In a recent study we used a Human stromal cell co-culture system to enhance survival of CLL cells cultured ex vivo. Resulting data demonstrated that although stromal co-culture increased resistance to mitoxantrone, it did not affect enhancement of mitoxantrone-induced cytotoxicity by the DNA-PK inhibitor (Elliott et al, British Journal of Haematology 2010). These data indicate the potential of targeting DNA-PK, even in the protective environment of stromal cells, which mimics the in vivo CLL lymphocyte microenvironment.
Recently awarded funding will allow us to explore the consequence of TP53 mutations, which occur in approximately 10% of CLL patients and can confer a particularly poor prognosis. In collaboration with David Oscier (Bournemouth) we will investigate the long term impact of TP53 mutations in CLL, since our preliminary data indicates that a subset of patients have unusually stable disease. In collaboration with Andy Pettitt (Liverpool) we will use proliferating CLL cells to investigate the effect of DNA-PK inhibition, and resulting DNA damage and chromosomal instability in replicating cells. Our current hypothesis is that increased non homologous end joining (the pathway mediated by DNA-PK) occurs by virtue of increased DNA-PK activity and generates genomic instability resulting in chromosomal abnormalities and mutations.
In collaboration with Tanja Stankovic (Birmingham) we are examining the potential of targeting DNA-PK in a background of ATM-deficient CLL. ATM dysfunction is frequent in CLL and occurs via chromosomal loss [del(11q)] and ATM mutation. We hypothesised that in ATM-defective CLL that already has one DNA damage-sensing pathway compromised, that targeting DNA-PK would completely compromise the CLL cells ability to repair chemotherapy-induced DNA damage. Our recent data confirms that ATM deficient mutant cells, although highly chemoresistant, are re-sensitised to Fludarabine by combination with a DNA-PK inhibitor. Current work is examining the mechanism by which this enhanced sensitisation occurs.
In addition to the research on CLL, other team members are studying the stress-inducible transcription factor, NF-κB. Constitutive activation of NF-κB is frequent in many cancers, and results in increased transcriptional activity leading to increased expression of a plethora of genes. Of the groups of genes whose expression is altered by aberrant NF-κB activity, one of the most important is the anti-apoptotic genes (e.g.Bcl2, Mcl1) which result in decreased apoptosis, chemo- and radio-resistance and ultimately tumour progression. In our lab, we used NF-κB null cell line models to investigate the role of NF-κB in the response to DNA damage. This work showed that ionising radiation-induced NF-κB activation requires poly(ADP-ribose) polymerase (PARP-1) function to confer radioresistance (Veuger et al, Oncogene 2009). Recent work using siRNA confirmed that PARP-1 mediates its effects on cell survival via NF-κB (Hunter et al, Oncogene 2012), most likely regulated by PAR polymer formation. Since these (and other unpublished data) point to a role for NF-κB in the DNA damage response, our ultimate goal is to target this aspect of NF-κB-directed transcriptional activity, to restore sensitivity to chemo- and radiotherapy. In collaboration with Chris Pepper (Cardiff) and Neil Perkins (Newcastle) we are pursing the potential of targeting DNA damage activated NF-κB in the context of CLL and other tumour types.

Future Research

Microtubule-targeting drugs are widely used for cancer treatment. Vincristine is important in childhood leukaemia and taxanes are used to treat breast and ovarian cancer. Unfortunately, drug resistance is a major problem. Emerging evidence supports a role for ATM and DNA-PK in this context, since they localise to centrosomes at mitosis, and ATM is activated by mitotic stress. A new project funded by CR UK will study the role that DNA-PK and ATM play in the mitotic spindle checkpoint, and we will elucidate the mechanisms by which ATM and DNA-PK impact on microtubule function and evaluate the potential of therapeutic targeting.

Postgraduate Supervision

6 previous PhD students (2002-11), 4 current PhD students: Emily Mould (2010-14), Laura Evans (2010-13) Gesa Junge (2012-15), Helen Marr (2011-14)

MRes: 10 previous MRes students (2005-2012), 1 current student :Stephanie Burnell (2013)

Esteem Indicators

Reviewer for various journals (Mol Cancer Therapeutics, Blood, Cancer Chemother & Pharmacol, Eur J Cancer, Pharm Research etc.) & Funding bodies (Leukaemia & Lymphoma Research Fund, MRC, YCR).

Invited speaker, CLL forum (London, 2005, 2007, 2008), University of Liverpool (2006), 'Haematological Malignancies' (London 2009) and NCRI annual meeting (2009).

Visiting Scientist to Prof. W. Plunkett's laboratory in the MD Anderson Cancer Center, Houston, Texas (summer 2006).


£46,591 (2013) Tyneside Leukaemia Research Association The role of poly(ADP-ribose) polymerase activity in chronic lymphocytic leukaemia. Project grant to Elaine Willmore & Nicola Curtin 

£108,138 (2010-2014)MRC Case studentship with AstraZenenca.
An evaluation of the potential of DNA-dependent protein kinase as a therapeutic target in chronic lymphocytic leukaemia. Elaine Willmore, Herbie Newell & Sylvie Guichard

£93,975 (2010-13) Leukaemia & Lymphoma Research.
Targeting DNA damage response proteins to overcome chemoresistance in
chronic lymphocytic leukaemia. Project grant to Elaine Willmore & Herbie Newell

£105,055 (2010-14) CR-UK. The roles of DNA-PK and ATM in the cellular responses to Microtubule-targeting drugs. PhD Studentship to Elaine Willmore & Herbie Newell.

£191,948 (2009-2012) Kay Kendall Leukaemia Fund. Role of DNA damage-activated enzymes as mediators of NF-κB activation in B-cell chronic lymphocytic leukaemia. Project grant to B.Durkacz, E Willmore & S Veuger.

£37,533, 2007-8, Newcastle Healthcare Charity. Enhancing sensitivity to DNA damaging agents in acute myeloid leukaemia cells by inhibition of DNA damage-activated kinases. Project grant to E. Willmore, S.J. Veuger & B.W. Durkacz.

£322,852, 2007-10, Leukaemia Research Fund. Targeting DNA damage-inducible kinases in poor prognosis Chronic Lymphocytic Leukaemia. Project grant to E. Willmore, BW Durkacz, GP Summerfield & T. Stankovic

£162,248, 2006-9, Leukaemia Research Fund. The role of DNA damage-inducible kinases in the cellular responses to nucleoside analogues used in leukaemia therapy. Project grant to E. Willmore, BW Durkacz, IG Cowell & GP Summerfield.

£105,396, 2006-10, Cancer Research UK. Investigation of the role of poly(ADP-ribose)polymerase (PARP) inhibition in topoisomerase I (topo I) poison-induced cytotoxicity. Studentship to NJ Curtin & E Willmore.

£56,931, 2005-8, Tyneside Leukaemia Research Fund. ATM and p53 status and inhibition of DNA damage-activated kinases in the responses of CLL to nucleoside analogues. Studentship to E. Willmore & BW Durkacz.

£173,414, 2004-7, Leukaemia Research Fund. Recombinational repair pathways as novel targets for therpaeutic intervention in CLL. Project grant to BW Durkacz, E.Willmore, CA Austin & GH Jackson.

£151,737, 2002-4, Leukaemia Research Fund. Evaluation of novel approaches to AML therapy. Project grant to C.A.Austin, E.Willmore, M.J.Tilby, B.W. Durkacz.

£148,564 1999-2002, Leukaemia Research Fund. Improving chemotherapy for AML in the elderly via optimisation of regimens containing topoisomerase II agents. Project grant to C.A. Austin, E. Willmore, M.J. Tilby & S.J. Proctor.

Industrial Relevance

Research collaborations currently with Astex Pharmaceuticals, AstraZeneca and formerly with Xenova

Undergraduate Teaching

BGM237 module, 2004-5 (Biochemistry & drug targets)
PED3006 module, 2009 onwards (Pharmacology, DNA repair & Cancer)

Postgraduate Teaching

Previous PhD student supervision Fiona Errington (2002), Andrew Jobson (2004), Lisa Smith (2004), Clark Crawford (2009), Jill Hunter (2007-11), Pawel Znojek (2006-11)
MRes students:
Yuanyuan Qiao (2005), Anthony Cutts (2006), Rob Hollingworth (2008), Attia Ashraf (2008), Arabella Baird (2009), Almahdi Jaber, Harpreet Sandhu (2010), Stephanie Burnell (2013)

Current PhD students:

Laura Evans (2010-13), Emily Mould (2010-14), Gesa Junge (2011-15), Helen Marr (Clinical Fellow, 2011-14)