Dr Elaine Willmore
Senior Research Associate
- Email: email@example.com
- Telephone: +44 (0) 191 208 4447
- Fax: +44 (0) 191 208 4301
- Address: Northern Institute for Cancer Research
University of Newcastle upon Tyne
Newcastle upon Tyne
Roles and Responsibilities
- Institute Biological Safety Officer
Areas of expertise
- Chronic Lymphocytic Leukaemia
- DNA damage and repair
- Drug and discovery
- Bsc (hons) Manchester, 1985
- PhD Newcastle, 1994
- 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.
- 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.
SCOPUS: Click here.
Development of novel therapeutics for Chronic Lymphocytic leukaemia
DNA Repair enzymes as targets for therapeutic intervention in chronic lymphocytic leukaemia and other tumour types
Investigating novel experimental therapeutic strategies using ex-vivo primary leukaemia and normal cells.
DNA repair pathways and associated methods for quantitative analysis.
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.
10 previous PhD students (2002-16), 3 current PhD students.
MRes: 14 previous MRes students (2005-2016)
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).
(2018) Newcastle Cancer Centre PhD studentship. An investigation of AR-V involvement in DNA damage repair and prostate cancer progression. Awarded to Stuart McCracken, Elaine Willmore, Ian Hickson & Luke Gaughan.
56,447.81 (2016) JGW Patterson Foundation. Exploiting the MDM2-p53 signalling network for biomarker studies and targeted treatment in chronic lymphocytic leukaemia (CLL). Award to John Lunec & Elaine Willmore
£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.
Research collaborations currently with Astex Pharmaceuticals, and formerly with AstraZeneca and Xenova
BGM237 module, 2004-5 (Biochemistry & drug targets)
PED3006 module, 2009 onwards (Pharmacology, DNA repair & Cancer)
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)
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), Holly Appleby (2017), Katie Barker (2018)
Current PhD students: Erhan Aptullahoglu (2016-18), Mohammed Howladar (2018-21), TBA (2018-21)
- Ciardullo C, Willmore E, Enshaei A, Zhou P, Rand V, Soundararajan M, Hall A, Harrison C, Eswaran J. BACH2 and BCL6 Cooperatively Fuction as Tumour Suppressors in CLL. In: 21st Congress of the European Hematology Association. 2016, Copenhagen, Denmark: Ferrata Storti Foundation.
- Ciardullo C, Zhou P, Willmore E, Harrison CJ, Hall A, Eswaran J, Soundararajan M. Impact of the apoptotic regulator DRAK2 in chronic lymphocytic leukemia. In: XXXVI World Congress of the International Society of Hematology. 2016, Glasgow: Wiley-Blackwell.
- Ciardullo C, Willmore E, Zhou P, Rand V, Harrison C, Hall A, Eswaran J, Soundararajan M. Impact of the apoptotic regulator DRAK2 in chronic lymphocytic leukemia. In: 21st Congress of the European Hematology Association. 2016, Copenhagen, Denmark: Fondazione Ferrata Storti.
- Barrow TM, Woodhouse L, Junge G, Tudhope SJ, Behardien C, Wallis JP, Marr HJ, Marshall SR, Bown N, Willmore E, Strathdee G. The Role of HOXA4 in Chronic Lymphocytic Leukaemia Progression and Response to Therapy. In: American Society of Hematology (ASH) 58th Annual Meeting & Exposition. 2016, San Diego, CA (USA): American Society of Hematology.
- Woodhouse L, Crawford C, Marshall S, Bown N, Wallis J, Summerfield G, Willmore E, Lunec J. Assessment and targeting of the MDM2-p53 network in CLL. In: AACR 106th Annual Meeting. 2015, Philadelphia, PA: American Association for Cancer Research.
- Willmore E, Gardner A, Tudhope S, Murtani B, Caffry J, Mulligan E, Hunter J, Wallis J, Marr H, Beretta G, Breen D, Paul A, Edwards D, Young L, Suckling C, Plevin R, Boyd M, Mackay S, Perkins N. Novel small molecule IKK alpha inhibitors inhibit non- canonical NF-kappa B signaling and survival of primary CLL cells. In: XVI International Workshop on Chronic Lymphocytic Leukemia. 2015, Sydney, Australia: Taylor & Francis.
- Herriott A, Tudhope SJ, Junge G, Rodrigues N, Patternson MJ, Woodhouse L, Lunec J, Hunter JE, Mulligan EA, Cole M, Allinson LM, Wallis JP, Marshall S, Wang E, Curtin NJ, Willmore E. PARP1 expression, activity and ex vivo sensitivity to the PARP inhibitor, talazoparib (BMN 673), in Chronic Lymphocytic Leukaemia. Oncotarget 2015, 6(41), 43978-43991.
- Evans L, Chen L, Milazzo G, Gherardi S, Perini G, Willmore E, Newell DR, Tweddle DA. SKP2 is a direct transcriptional target of MYCN and a potential therapeutic target in neuroblastoma. Cancer Letters 2015, 363(1), 37-45.
- Shouksmith AE, Evans LE, Tweddle DA, Miller DC, Willmore E, Newell DR, Golding BT, Griffin RJ. Synthesis and Activity of Putative Small-Molecule Inhibitors of the F-Box Protein SKP2. Australian Journal of Chemistry 2015, 68(4), 660-679.
- Mould E, Berry P, Jamieson D, Hill C, Cano C, Tan N, Elliott S, Durkacz B, Newell D, Willmore E. Identification of dual DNA-PK MDR1 inhibitors for the potentiation of cytotoxic drug activity. Biochemical Pharmacology 2014, 88(1), 58-65.
- Znojek P, Willmore E, Curtin NJ. Preferential potentiation of topoisomerase I poison cytotoxicity by PARP inhibition in S phase. British Journal of Cancer 2014, 111(7), 1319-1326.
- Iannetti A, Ledoux AC, Tudhope SJ, Sellier H, Zhao B, Mowla S, Moore A, Hummerich H, Gewurz BE, Cockell SJ, Jat PS, Willmore E, Perkins ND. Regulation of p53 and Rb Links the Alternative NF-kappa B Pathway to EZH2 Expression and Cell Senescence. PLoS Genetics 2014, 10(9).
- Amin S, Walsh M, Wilson C, Parker AE, Oscier D, Willmore E, Mann D, Mann J. Cross-talk between DNA methylation and active histone modifications regulates aberrant expression of ZAP70 in CLL. Journal of Cellular and Molecular Medicine 2012, 16(9), 2074-2084.
- Hunter JE, Willmore E, Irving JAE, Hostomsky Z, Veuger SJ, Durkacz BW. NF-kappa B mediates radio-sensitization by the PARP-1 inhibitor, AG-014699. Oncogene 2012, 31(2), 251-264.
- Elliott SL, Crawford C, Mulligan E, Summerfield G, Newton P, Wallis J, Mainou-Fowler T, Evans P, Bedwell C, Durkacz BW, Willmore E. Mitoxantrone in combination with an inhibitor of DNA-dependent kinase: a potential therapy for high risk B-cell chronic lymphocytic leukaemia. British Journal of Haematology 2011, 152(1), 61-71.
- Sunter NJ, Cowell IG, Willmore E, Watters GP, Austin CA. Role of Topoisomerase IIbeta in DNA Damage Response following IR and Etoposide. Journal of Nucleic Acids 2010, 710589.
- Lopez-Lazaro M, Willmore E, Austin CA. The dietary flavonoids myricetin and fisetin act as dual inhibitors of DNA topoisomerases I and II in cells. Mutation Research - Genetic Toxicology and Environmental Mutagenesis 2010, 696(1), 41-47.
- Willmore E, Elliott SL, Mainou-Fowler T, Summerfield GP, Jackson GH, O'Neill F, Lowe C, Carter A, Harris R, Pettitt AR, Cano-Soumillac C, Griffin RJ, Cowell IG, Austin CA, Durkacz BW. DNA-dependent protein kinase is a therapeutic target and an indicator of poor prognosis in B-cell chronic lymphocytic leukemia. Clinical Cancer Research 2008, 14(12), 3984-3992.
- Jobson, A., Willmore, E., Tilby, M.J., Mistry, P., Charlton, P, Austin, C. Effect of phenazine compounds XR11576 and XR5944 on DNA topoisomerases. Cancer Chemotherapy and Pharmacology 2008, 63(5), 1-13.
- López-Lázaro M, Willmore E, Elliott SL, Austin CA. Selenite induces topoisomerase I and II-DNA complexes in K562 leukemia cells. International Journal of Cancer 2008, 123(9), 2217-2221.
- López-Lázaro, M., Willmore, E., Austin, C. A. Cells lacking DNA topoisomerase IIβ are resistant to genistein. Journal of Natural Products 2007, 70(5), 763-767.
- López-Lázaro M, Willmore E, Jobson AG, Gilroy KL, Curtis H, Padget K, Austin CA. Curcumin induces high levels of topoisomerase I- and II-DNA complexes in K562 leukemia cells. Journal of Natural Products 2007, 70(12), 1884-1888.
- Smith LM, Willmore E, Austin C, Curtin NJ. The novel poly(ADP-ribose) polymerase inhibitor, AG14361 sensitizes cells to topoisomerase I poisons by increasing the persistence of DNA strand breaks. Clinical Cancer Research 2005, 11(23), 8449-8457.
- Willmore, E., De Caux, S., Sunter, N., Tilby, M.J., Jackson, G., Austin, C., Durkacz, B.W. A novel DNA-dependent protein kinase inhibitor, NU7026, potentiates the cytotoxicity of topoisomerase II poisons used in the treatment of leukemia. Blood 2004, 103(12), 4659-4665.
- Errington, F., Willmore, E., Leontiou, C., Tilby, M., Austin, C. Differences in the longevity of topo IIα and topo IIβ drug-stabilized cleavable complexes and the relationship to drug sensitivity. Cancer Chemotherapy and Pharmacology 2004, 53(2), 155-162.
- Pors, K., Paniwnyk, Z., Teesdale-Spittle, P., Plumb, J. A., Willmore, E., Austin, C. A., Patterson, L. H. Alchemix: A novel alkylating anthraquinone with potent activity against anthracycline- and cisplatin-resistant ovarian cancer. Molecular Cancer Therapeutics 2003, 2(7), 607-610.
- West, K. L., Turnbull, R. M., Willmore, E., Lakey, J. H., Austin, C. A. Characterisation of the DNA-dependent ATPase activity of human DNA topoisomerase IIß: mutation of Ser165 in the ATPase domain reduces the ATPase activity and abolishes the in vivo complementation ability. Nucleic Acids Research 2002, 30(24), 5416-5424.
- Willmore, E., Errington, F., Tilby, M.J., Austin, C.A. Formation and longevity of idarubicin-induced DNA topoisomerase II cleavable complexes in K562 human leukaemia cells. Biochemical Pharmacology 2002, 63(10), 1807-1815.
- Errington F, Willmore E, Tilby MJ, Li L, Li G, Li W, Baguley B, Austin CA. Murine transgenic cells lacking DNA topoisomerase IIβ are resistant to acridines and mitoxantrone: Analysis of cytotoxicity and cleavable complex formation. Molecular Pharmacology 1999, 56(6), 1309-1316.
- Willmore, E., Frank, A., Padget, K., Tilby, M.J., Austin, C.A. Etoposide targets topoisomerase IIα and IIβ in leukemic cells: Isoform-specific cleavable complexes visualized and quantified in situ by a novel immunofluorescence technique. Molecular Pharmacology 1998, 54(1), 78-85.
- Cowell IG, Willmore E, Chalton DA, Marsh KL, Jazrawi E, Fisher LM, Austin CA. Nuclear distribution of human DNA topoisomerase IIβ: A nuclear targeting signal resides in the 116-residue C-terminal tail. Experimental Cell Research 1998, 243(2), 232-240.
- Marsh, K. L., Willmore, E., Tinelli, S., Cornarotti, M., Meczes, E., Capranico, G., Fisher, L. M., Austin, C. A. Amsacrine-promoted DNA cleavage site determinants for the two human DNA topoisomerase II isoforms α and β. Biochemical Pharmacology 1996, 52(11), 1675-1685.
- Cornarotti, M., Tinelli, S., Willmore, E., Zunino, F., Fisher, L. M., Austin, C. A., Capranico, G. Drug sensitivity and sequence specificity of human recombinant DNA topoisomerases IIα (p170) and IIβ (p180). Molecular Pharmacology 1996, 50(6), 1463-1471.
- Bigioni, M., Zunino, F., Tinelli, S., Austin, C. A., Willmore, E., Capranico, G. Position-specific effects of base mismatch on mammalian topoisomerase II DNA cleaving activity. Biochemistry 1996, 35(1), 153-159.
- Austin CA, Marsh KL, Wasserman RA, Willmore E, Sayer PJ, Wang JC, Fisher LM. Expression, domain structure and enzymatic properties of an active recombinant human DNA topoisomerase II beta. Journal of Biological Chemistry 1995, 270(26), 15739-15746.
- Jones S, Willmore E, Durkacz BW. The effects of 5-fluoropyrimidines on nascent DNA synthesis in Chinese hamster ovary cells monitored by pH-step alkaline and neutral elution. Carcinogenesis 1994, 15(11), 2435-8.
- Willmore E, Durkacz BW. Cytotoxic mechanisms of 5-fluoropyrimidines: Relationships with poly(ADP-ribose) polymerase activity, DNA strand breakage and incorporation into nucleic acids. Biochemical Pharmacology 1993, 46(2), 205-211.
- Moses K, Willmore E, Harris AL, Durkacz BW. Correlation of enhanced 6-mercaptopurine cytotoxicity with increased phosphoribosylpyrophosphate levels in Chinese hamster ovary cells treated with 3-aminobenzamide. Cancer Research 1990, 50(7), 1992-1996.