Professor Thomas Helleday

Department of Oncology and Metabolism

Professor of Translational Oncology

Director of the Weston Park Cancer Centre

Thomas Helleday
t.helleday@sheffield.ac.uk
+44 114 215 9677
+44 114 215 9248 (Personal assistant, Lisa Graham)

Full contact details

Professor Thomas Helleday
Department of Oncology and Metabolism
FU24, F Floor
The Medical School
Beech Hill Road
Sheffield
S10 2RX
Profile

After being awarded separate degrees in molecular biology, business administration and economics I continued as a postgraduate student and completed my PhD at Stockholm University for studies on homologous recombination in mammalian cells.

In 1999 I joined the University of Sheffield as a post-doctoral researcher and was soon after appointed to a lectureship to set up a research group. I was then promoted to Professor in Cancer Genetics at the University of Sheffield in 2006, which was followed by my recruitment as MRC Professor of Cancer Therapeutics at the MRC/CRUK Institute for Radiation Oncology and Biology at the University of Oxford in 2007. From 2012 I have been Torsten and Ragnar Söderberg Professor of Translational Medicine and Chemical Biology at the Science for Life Laboratory at the Karolinska Institutet in Stockholm. I have recently moved back to Sheffield and I am Professor of Translational Oncology and founding Director of the Weston Park Cancer Centre.

Over the years I have won a number of prestigious international awards including twice European Research Council Advanced Research Programme Awards, The Eppendorf-Nature Young European Investigator Award (by journal Nature), European Association for Cancer Research (EACR) Young Cancer Researchers Award, Carcinogenesis Young Investigator Award and Swiss Bridge Award.

Research interests

I head a multidisciplinary translational research group focusing on understanding basic DNA repair and DNA-damage signalling pathways at replication forks and developing novel drugs for anti-cancer treatments. The group was first to demonstrate a novel concept for treating cancer called “synthetic lethality” established by the selective killing of BRCA mutated breast and ovarian cancers by PARP inhibitors. The research group is currently divided into teams focusing on basic science, biology, biochemistry, medicinal chemistry, in vivo pharmacology and clinical development. The work is focussed on bench to bedside with the group motto being ‘turning cancer defects into cures’. Compounds generated in the Helleday laboratory are currently tested in clinical trials.

We are working tremendously hard to ensure that innovative and transformative treatments get quickly and effectively from our research laboratories into the clinic to ensure maximum patient benefit.

Current projects:

1) OGG1 –We developed first-in-class OGG1 inhibitors that we are progressing in lead optimisation for treatments of inflammation and to further understand the detailed role in DNA repair. We are also exploring OGG1 as a potential treatment of cancer.
2) MTHFD2 – We are exploring novel biological roles of MTHFD2 and we have generated potent inhibitors to this target that show extraordinary anti-cancer properties. We are fast-tracking MTHFD2 inhibitors into the clinic.
3) MTH1 – We have identified novel functions of MTH1 in mitosis and have made potent MTH1 inhibitors one of which, karonudib, is currently evaluated in clinical phase I trials and is set to enter into phase II trials in the short future.
4) NUDT22 –is an understudied enzyme and we have identified its biochemical and biological function. We have generated potent NUDT22 inhibitors to test for treatment applications and to further expand our understanding of the role of the enzyme.
5) Base excision repair proteins – we are purifying a number of DNA glycosylases and other base excision repair proteins and are probing their biochemical role to develop inhibitors, which may be applied for treatment of human diseases.
6) Ex vivo screening – we are embracing a novel method using advanced microscopy to better tailor cancer treatments to patients to more rapidly and effectively deliver treatments. We are convinced this will set a new paradigm for precision cancer medicine.

Publications

Journal articles

Chapters

Conference proceedings papers

  • Helleday T (2020) Abstract ES12-2: Targeted DNA repair in cancer and new NUDT5 inhibitors to block hormone signalling to target breast cancer. Invited Speaker Abstracts RIS download Bibtex download
  • Helleday T (2019) Targeting DNA Repair: Beyond Cancer.. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Vol. 60 (pp 44-45) RIS download Bibtex download
  • Sanjiv K, gad H, Rudd SG, Mortusewicz O, Stolz A, Amaral N, Brautigham L, Pudelko L, Kaldéren C, Jemth A-S , Almlöf I et al (2019) Abstract 105: MTH1 promotes mitotic progression to avoid oxidative DNA damage in cancer cells. Tumor Biology RIS download Bibtex download
  • Sanjiv K, gad H, Rudd SG, Mortusewicz O, Stolz A, Amaral N, Brautigham L, Pudelko L, Kaldéren C, Jemth A-S , Almlöf I et al (2019) Abstract 105: MTH1 promotes mitotic progression to avoid oxidative DNA damage in cancer cells. Tumor Biology RIS download Bibtex download
  • Rudd SG, Paulin CB, Nikolaos T, Sanjiv K, Juliane K, Myrberg IH, Axelsson H, Rasti A, Witta E, Lee S , Rassidakis GZ et al (2018) CRISPR Screen Identifies MAD1L1, CDC27 and CDC42 as Determinants of Sensitivity to Sonic Hedgehog Inhibitor Sonidegib in Medulloblastoma Cell Lines. PEDIATRIC BLOOD & CANCER, Vol. 65 (pp S419-S420) RIS download Bibtex download
  • Hansel C, Hlouschek J, Helleday T, Jendrossek V & Matschke J (2018) Combined inhibition of GSH levels and sanitization of dNTPs is effective in eradicating cancer cells exposed to acute hypoxia or chronic cycling severe hypoxia. STRAHLENTHERAPIE UND ONKOLOGIE, Vol. 194 (pp S172-S172) RIS download Bibtex download
  • Das I, Gad H, Pudelko L, Brautigam L, Tuominen R, Helleday T, Hansson J, Brage S & Berglund U (2018) Effects of MTH1 inhibitor TH1579 on cutaneous melanoma. JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol. 138(5) (pp S200-S200) RIS download Bibtex download
  • Herold N, Rudd S, Myrberg IH, Sanjiv K, Ljungblad L, Kutzner J, Grander D, Kogner P, Rassidakis G, Helleday T , Henter JI et al (2017) Development of a Small Molecule Inhibitor for SAMHD1 to Improve Outcome for Patients with Acute Myelogenous Leukaemia and Relapsed T-Lymphoblastic Malignancies Treated with Nucleoside Analogues. PEDIATRIC BLOOD & CANCER, Vol. 64 (pp S135-S135) RIS download Bibtex download
  • Helleday T (2017) Poisoning cancer with oxidized nucleotides by targeting MTH1. MOLECULAR CANCER RESEARCH, Vol. 15 RIS download Bibtex download
  • Hurley R, Wagner J, Schneider P, Hou X, Becker M, Sanjiv K, Berglund UW, Kaufmann S, Weroha SJ, Helleday T & Hendrickson AW (2016) INVESTIGATING THE ROLE OF MTH1 INHIBITION IN THE TREATMENT OF OVARIAN CANCER. INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol. 26 (pp 727-727) RIS download Bibtex download
  • Coskun E, Jaruga P, Jemth A, Loseva O, Leona SD, Tona A, Lowenthal MS, Reddy PT, Helleday T & Dizdaroglu M (2016) Introducing a new method for absolute quantification of DNA repair proteins in relation to drug development: LC–MS/MS with isotope dilution. Toxicology Letters, Vol. 258 (pp S57-S57) RIS download Bibtex download
  • Asim M, Zecchini H, Tarish F, Massie C, Baridi A, Warren A, Zhao W, McDuffus L-A, Mascalchi P, Shaw G , Dev H et al (2016) Abstract LB-176: The human androgen receptor regulates DNA damage response (DDR) in prostate cancer. Tumor Biology RIS download Bibtex download
  • Sanjiv K, Gad H, Rudd S, Hurley R, Herr P, Montaño JMC, Mortusewicz O, Koolmeister T, Jaques S, Morón EB , Hoglund A et al (2016) Abstract 1260: Polymerase kappa determines the sensitivity of MTH1 inhibitors to cisplatin-resistant cell. Experimental and Molecular Therapeutics RIS download Bibtex download
  • Lallo A, Berglund UW, Frese K, Potter D, Helleday T & Dive C (2016) Ex vivo culture of circulating tumour cell derived explants to facilitate rapid therapy testing in small cell lung cancer. EUROPEAN JOURNAL OF CANCER, Vol. 61 (pp S120-S120) RIS download Bibtex download
  • Pompsch M, Brokmeier U, Riffkin H, Kranz P, Baumann M, Goepelt K, Classen F, Wolf A, Berglund U, Helleday T & Metzen E (2016) Inhibition of the nucleotide pool sanitizing enzyme MTH1 augments genotoxic effects of ionizing radiation and hypoxia on tumor cells. ACTA PHYSIOLOGICA, Vol. 216 RIS download Bibtex download
  • Helleday T (2015) MTH1 inhibitors in cancer treatment. Annals of Oncology, Vol. 26 (pp ii8-ii8) RIS download Bibtex download
  • Orta Vazquez ML, Ruiz-Castizo A, Pastor Carrillo N, Dominguez Garcia I, Vargas Duarte MDP, Burgos-Moron E, Manzano-Lopez J, Manuel Calderon-Montano J, Hoeglund A, Muniz Guinea M , Lopez-Lazaro M et al (2014) 5-aza-2 ' deoxycytidine induces DNA lesions that are repaired via Transcription-Coupled Repair involving Cockayne syndrome protein B. MUTAGENESIS, Vol. 29(6) (pp 533-533) RIS download Bibtex download
  • Sanjiv K, Hagenkort A, Reaper PM, Koolmeister T, Mortusewicz O, Schultz N, Scobie M, Berglund UW, Charlton PA, Pollard JR & Helleday T (2014) 240 The combination of Chk-1 and ATR inhibitor synergistically kills cancer cells. European Journal of Cancer, Vol. 50 (pp 81-81) RIS download Bibtex download
  • Orta Vazquez ML, Hoglund A, Calderon Montano JM, Pastor N, Dominguez I, Strom C, Burgos Moron E, Lopez-Lazaro M & Helleday T (2014) The PARP inhibitor Olaparib disrupts Base Excision Repair of 5-aza-2 '-deoxycytidine lesions. MUTAGENESIS, Vol. 29(6) (pp 541-542) RIS download Bibtex download
  • Orta Vazquez ML, Pastor Carrillo N, Dominguez Garcia I, Burgos-Moron E, Manuel Calderon-Montano J, Bejarano Garcia JA, Garcia-Dominguez I, Ruiz Castizo A, Vargas Duarte MDP, Lopez-Lazaro M , Helleday T et al (2014) Zebularine induces replication-dependent double-strand breaks which are preferentially repaired by Homologous Recombination. MUTAGENESIS, Vol. 29(6) (pp 534-534) RIS download Bibtex download
  • Braeutigam L, Fiskesund R, Warpman-Berglund U & Helleday T (2014) 365: The interplay between the redox environment, MTH1 and cancer. European Journal of Cancer, Vol. 50 (pp S87-S87) RIS download Bibtex download
  • Helleday T (2014) 6: Targeting MTH1 prevents sanitation of oxidised dNTP pools and causes cancer-selective DNA damage and cell death. European Journal of Cancer, Vol. 50 (pp S3-S3) RIS download Bibtex download
  • Berglund UW, Gad H, Jemth AS, Koolmeister T, Gokturk C, Pham T, Nilsson J, Eshtad S, Scobie M & Helleday T (2014) Inhibiting MTH1 kills cancer cells by preventing sanitisation of oxidised dNTP pool. EUROPEAN JOURNAL OF CANCER, Vol. 50 (pp S203-S203) RIS download Bibtex download
  • Helleday T (2013) Abstract CN05-04: Novel DNA repair targets for anticancer treatments.. DNA Repair and Modulation RIS download Bibtex download
  • Helleday T (2013) New DNA repair targets in cancer treatment. EUROPEAN JOURNAL OF CANCER, Vol. 49 (pp S38-S39) RIS download Bibtex download
  • Helleday T (2012) DNA repair pathways as target for cancer therapy. Toxicology Letters, Vol. 211 (pp S9-S9) RIS download Bibtex download
  • Petermann E, Jones RM, Orta ML, Issaeva N, Schultz N, Afzal I & Helleday T (2012) Interplay between DNA replication and the DNA damage response. MUTAGENESIS, Vol. 27(1) (pp 108-109) RIS download Bibtex download
  • Helleday T (2011) DNA Damage and Repair in Cancer: From Basic Science to Anti-Cancer Treatments.. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Vol. 52 (pp S13-S13) RIS download Bibtex download
  • Helleday T (2011) Transcription-Associated Recombination at Replication Forks in Mammalian Cells.. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Vol. 52 (pp S25-S25) RIS download Bibtex download
  • Helleday T (2011) 247 INVITED PARP Inhibitors Sensitivity and Resistance. European Journal of Cancer, Vol. 47 (pp S58-S58) RIS download Bibtex download
  • Al-Assar O, Mantoni TS, Lunardi S, Kingham G, Helleday T & Brunner TB (2011) Breast cancer stem-like cells show enhanced homologous recombination due to a larger S-G2 fraction. STRAHLENTHERAPIE UND ONKOLOGIE, Vol. 187 (pp 54-54) RIS download Bibtex download
  • Higgins GS, Prevo R, Lundin C, Helleday T, Buffa FM, Harris AL, Muschel RJ, Bernhard EJ, Hickson ID & McKenna WG (2010) 332 POLQ (DNA polyermase theta) as a novel therapeutic target: preclinical and clinical data. European Journal of Cancer Supplements, Vol. 8(7) (pp 106-106) RIS download Bibtex download
  • Helleday T (2010) THE INCREASING COMPLEXITY OF PARP FAMILY PROTEINS IMPLICATIONS FOR CANCER THERAPY. RADIOTHERAPY AND ONCOLOGY, Vol. 96 (pp S34-S34) RIS download Bibtex download
  • Somaiah N, Yarnold JR, Lagerqvist A, Daley F, Rothkamm K & Helleday T (2010) SENSITIVITY TO RADIOTHERAPY FRACTION SIZE IS MODULATED BY DNA DOUBLE STRAND BREAK (DSB) REPAIR SYSTEMS. RADIOTHERAPY AND ONCOLOGY, Vol. 96 (pp S154-S154) RIS download Bibtex download
  • Chatzakos V, Slätis K, Djureinovic T, Helleday T & Hunt MC (2010) Anti-proliferative effects of taurine conjugated fatty acids. Chemistry and Physics of Lipids, Vol. 163 (pp S36-S36) RIS download Bibtex download
  • Helleday T (2010) 611 Homologous recombination in cancer development, treatment and development of drug resistance. European Journal of Cancer Supplements, Vol. 8(5) (pp 156-156) RIS download Bibtex download
  • Fraser ME, Zhao H, Lundin C, Evans A, Helleday T & Bristow RG (2010) Loss of PTEN sensitizes cells to DNA damaging agents in a RAD51-independent manner. CANCER RESEARCH, Vol. 70 RIS download Bibtex download
  • Fraser ME, Zhao H, Lundin C, Evans A, Helleday T & Bristow RG (2010) Abstract 3932: Loss of PTEN sensitizes cells to DNA damaging agents in a RAD51-independent manner. Cellular and Molecular Biology RIS download Bibtex download
  • Somaiah N, Yarnold J, Daley F, Pearson A, Rothkamm K & Helleday T (2010) Radiotherapy fraction size sensitivity is modulated by DNA repair systems. Breast Cancer Research, Vol. 12(S1) RIS download Bibtex download
  • Chan N, Pires IM, Bencokova Z, Coackley C, Bhogal N, Lakshman M, Gottipati P, Oliver FJ, Helleday T, Hammond EM & Bristow RG (2009) Abstract A115: Contextual synthetic lethality: Repair‐deficient hypoxic tumor cells are sensitized to poly(ADP‐ribose) polymerase (PARP) inhibition. DNA Repair and Modulation RIS download Bibtex download
  • Helleday T (2009) 156 Exploiting cancer defects in targeted therapy. European Journal of Cancer Supplements, Vol. 7(2) (pp 39-39) RIS download Bibtex download
  • Issaeva N, Thomas HD, Pedley N, Djurenovic T, Lundin C, Gubanova E, Sleeth K, Stoimenov I, Chatzakos V, Zdzienicka MZ , Curtin NJ et al (2009) Exploiting Homologous Recombination Repair Defects in Cancer Cells. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Vol. 50(7) (pp 544-544) RIS download Bibtex download
  • Chatzakos V, Djureinovic T, Helleday T & Hunt M (2009) Anti-proliferative effects of glycine conjugated fatty acids. Chemistry and Physics of Lipids, Vol. 160 (pp S23-S23) RIS download Bibtex download
  • Helleday T (2009) Replication as origin for chromosome fragility - mechanistic insights.. CHROMOSOME RESEARCH, Vol. 17 (pp 16-16) RIS download Bibtex download
  • Hawtin R, Stockett D, Lundin C, Helleday T & Fox J (2009) Voreloxin is active in breast cancer biopsies and potency is enhanced in a BRCA2 mutant background. CANCER RESEARCH, Vol. 69 RIS download Bibtex download
  • Helleday T (2009) Recombination repair in bypass of replication blocks in mammalian cells. MUTAGENESIS, Vol. 24(1) (pp 100-100) RIS download Bibtex download
  • Helleday T (2008) EXPLOITING DNA REPAIR AS TARGET FOR IMPROVING RADIOTHERAPY. RADIOTHERAPY AND ONCOLOGY, Vol. 88 (pp S15-S15) RIS download Bibtex download
  • Petermann E & Helleday T (2007) DNA replication-associated lesions: importance in early tumorigenesis and cancer therapy. Biochemical Society Transactions, Vol. 35(5) (pp 1352-1354) RIS download Bibtex download
  • Helleday T (2007) 119 EACR award DNA replication repair: molecular insights towards new approaches to targeted anti-cancer therapy. European Journal of Cancer Supplements, Vol. 5(4) (pp 33-33) RIS download Bibtex download
  • Loseva O, Johansson A & Helleday T (2007) Identification of proteins relocated to the chromatin following DNA damage. FEBS JOURNAL, Vol. 274 (pp 79-79) RIS download Bibtex download
Teaching interests

I have supervised a total of 35 PhD students of which 27 have graduated so far (21 main supervisor, 6 co-supervisor). In addition I have supervised 31 postdocs as main supervisor and >70 final year degree workers.

At the University of Sheffield I am currently teaching on the Translational Oncology MSc course.

Professional activities

I am a member of several prestigious national and international committees and editorial boards (selected list):

- Member of the European Molecular Biology Organisation (EMBO)
- Fellow of the European Academy of Cancer Sciences
- Associated Editor and Member of Editorial Board, Annals of Oncology
- Member of Editorial Board, Cancer Research
- Member of Editorial Board, Molecular Oncology
- Member of Editorial Board, Molecular Cancer Research