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

Qualifications

Bsc (hons) Manchester, 1985
PhD Newcastle, 1994

Previous Positions

2006 Visiting Scientist, Dept of Exerimental Therpaeutics, MD Anderson Cancer Center, Houston, Texas.

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.

Memberships

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 and normal cells.
DNA repair pathways and associated methods for quantitative analysis

Current Work

Based in the Drug Discovery group in the Northern Institute for Cancer Research, I am interested in preclinical modelling using patient-derived material, and in particular targets for therapeutic intervention in B-cell chronic lymphocytic leukaemia (CLL).
Previously (in collaboration with AstraZeneca, and formerly KuDOS) we evaluated potent and specific inhibitors of DNA-PK, to build upon our observations that DNA-PK inhibition sensitised leukaemia cell lines to DNA Topoisomerase II-targeting agents (Willmore et al, Blood 2004).
CLL is a common haematological malignancy and although patients initially respond to current therapies (e.g. fludarabine, cyclophosphamide, rituximab), many eventually become resistant and some patients display more aggressive disease. Mechanisms of drug-resistance include alterations in DNA repair pathways (including defects in ATM and p53 and overexpression of DNA-PK). 
We demonstrated that patient-derived B-CLL cells are chemo- sensitised by DNA-PK inhibition, by mechanisms involving increased DNA damage due to inhibition of DNA-PK activation.  We also made the novel observation that DNA-PK over expression is associated with shorter survival in CLL (Willmore et al, Clinical Cancer Research, 2008) and that even in the protective environment of stromal cells, which mimics the in vivo CLL lymphocyte microenvironment, DNA-PK inhibition chemo-sensitised CLL cells.(Elliott et al, British Journal of Haematology 2011).
Recently we have explored the consequence of TP53 mutations, which occur in approximately 10% of CLL patients but increase in patients with refractory CLL, and confer a particularly poor prognosis. A collaboration with Professor John Lunec is examining the long term impact of TP53 mutations in CLL, since our data indicates that a subset of patients have unusually stable disease. For patients with normal p53 function, we are evaluating MDM2 antagonists as a potential non-genotoxic therapy.

We are also studying the stress-inducible transcription factor, NF-κB. Constitutive activation of NF-κB is frequent in cancer, and results in increased transcriptional activity leading to increased expression of a plethora of genes. In collaboration with Neil Perkins (Newcastle), Simon Mackay (Strathclyde) and Chris Pepper (Cardiff),we are investigating the potential of targeting the non-canonical (alternative) NF-κB pathway in the context of CLL and other tumour types.

Postgraduate Supervision

10 previous PhD students (2002-16), 1 current PhD student.

MRes: 14 previous MRes students (2005-2016)

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 (now 'Bloodwise'), MRC, YCR).

Invited speaker, CLL forum (London, 2005, 2007, 2008), University of Liverpool (2006), 'Haematological Malignancies' (London 2009), University of Southampton (2013) and NCRI annual meeting (2009).

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

Research Funding 

£56,318 (2016) Newcastle Healthcare Charity. Biomarker assessment and therapeutic targeting of the MDM2-p53 signalling network in chronic lymphocytic leukaemia. Award to John Lunec & Elaine Willmore 

£49,552 (2015) JGWP Foundation. Identification of epigenetic regulators of chemosensitivity in CLL. Award to Gordon Strathdee & Elaine Willmore

£39,748 (+fEC) (2014) MRC Confidence in Concept. Targeting IKKalpha in chronic lymphocytic leukaemia. Award to Simon Mackay, (Strathclyde University). Newcastle Collaborators: Elaine Willmore & Neil Perkins

£185,239 (2014) Leukaemia & Lymphoma Research.Clinical exploitation of HOXA4 status for directing treatment in CLL patients. Project grant to Gordon Strathdee & Elaine Willmore

 £26,775 (2014) Bright Red. Evaluation of the role of BACH2 in Lymphoid malignancies. Project grant to Andy Hall, Vikki Rand & Elaine Willmore                                       

£132,967 (2013-15) Leukaemia & Lymphoma Research. p53 mutation and functional status as predictive biomarkers to guide the treatment of CLL patients. Project grant to John Lunec & Elaine Willmore

£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, and formerly with AstraZeneca and 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),Emily Mould (2010-14),Laura Evans (2010-14), Gesa Junge (2011-15), Helen Marr (Clinical Fellow, 2011-15)


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), Jessica Caffry (2014), Belinda Murtani (2015), Andrew Herridge & Ben McCullough (2016)

Current PhD students: Erhan Aptullahoglu (2016-18)