Professor Thomas Helleday

Professor of Translational Oncology, Director of the Weston Park Cancer Centre T Helleday
Department of Oncology & Metabolism
The Medical School
Beech Hill Road
SHEFFIELD
S10 2RX


For admin assistance please contact

Personal Assistant: Lisa Graham

Telephone: (0)114 215 9248
Email: lisa.graham@sheffield.ac.uk

Email: t.helleday@sheffield.ac.uk
Telephone: +44 (0)114 215 9677 (Internal Ext: 59677)

Biography

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.

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

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.

Key publications

1. Visnes T, Cazares-Korner A, Hao W, Wallner O, Masuyer G, Loseva O, Mortusewicz O, Wiita E, Sarno A, Manoilov A, Astorga-Wells J, Jemth AS, Pan L, Sanjiv K, Karsten S, Gokturk C, Grube M, Homan EJ, Hanna BMF, Paulin CBJ, Pham T, Rasti A, Berglund UW, von Nicolai C, Benitez-Buelga C, Koolmeister T, Ivanic D, Iliev P, Scobie M, Krokan HE, Baranczewski P, Artursson P, Altun M, Jensen AJ, Kalderen C, Ba X, Zubarev RA, Stenmark P, Boldogh I, Helleday T. Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation. Science. 2018;362(6416):834-9.

2. Page BDG, Valerie NCK, Wright RHG, Wallner O, Isaksson R, Carter M, Rudd SG, Loseva O, Jemth AS, Almlof I, Font-Mateu J, Llona-Minguez S, Baranczewski P, Jeppsson F, Homan E, Almqvist H, Axelsson H, Regmi S, Gustavsson AL, Lundback T, Scobie M, Stromberg K, Stenmark P, Beato M, Helleday T. Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells. Nat Commun. 2018;9(1):250.

3. Gustafsson NMS, Farnegardh K, Bonagas N, Ninou AH, Groth P, Wiita E, Jonsson M, Hallberg K, Lehto J, Pennisi R, Martinsson J, Norstrom C, Hollers J, Schultz J, Andersson M, Markova N, Marttila P, Kim B, Norin M, Olin T, Helleday T. Targeting PFKFB3 radiosensitizes cancer cells and suppresses homologous recombination. Nat Commun. 2018;9(1):3872.

4. Vladimer GI, Snijder B, Krall N, Bigenzahn JW, Huber KVM, Lardeau CH, Sanjiv K, Ringler A, Berglund UW, Sabler M, de la Fuente OL, Knobl P, Kubicek S, Helleday T, Jager U, Superti-Furga G. Global survey of the immunomodulatory potential of common drugs. Nat Chem Biol. 2017;13(6):681-+.

5. Herold N, Rudd SG, Ljungblad L, Sanjiv K, Myrberg IH, Paulin CB, Heshmati Y, Hagenkort A, Kutzner J, Page BD, Calderon-Montano JM, Loseva O, Jemth AS, Bulli L, Axelsson H, Tesi B, Valerie NC, Hoglund A, Bladh J, Wiita E, Sundin M, Uhlin M, Rassidakis G, Heyman M, Tamm KP, Warpman-Berglund U, Walfridsson J, Lehmann S, Grander D, Lundback T, Kogner P, Henter JI, Helleday T, Schaller T. Targeting SAMHD1 with the Vpx protein to improve cytarabine therapy for hematological malignancies. Nat Med. 2017;23(2):256-63.

6. Carreras-Puigvert J, Zitnik M, Jemth AS, Carter M, Unterlass JE, Hallstrom B, Loseva O, Karem Z, Calderon-Montano JM, Lindskog C, Edqvist PH, Matuszewski DJ, Blal HA, Berntsson RPA, Haggblad M, Martens U, Studham M, Lundgren B, Wahlby C, Sonnhammer ELL, Lundberg E, Stenmark P, Zupan B, Helleday T. A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family. Nature Communications. 2017;8.

7. Asim M, Tarish F, Zecchini HI, Sanjiv K, Gelali E, Massie CE, Baridi A, Warren AY, Zhao WF, Ogris C, McDuffus LA, Mascalchi P, Shaw G, Dev H, Wadhwa K, Wijnhoven P, Forment JV, Lyons SR, Lynch AG, O'Neill C, Zecchini VR, Rennie PS, Baniahmad A, Tavare S, Mills IG, Galanty Y, Crosetto N, Schultz N, Neal D, Helleday T. Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer. Nature Communications. 2017;8.

8. Sanjiv K, Hagenkort A, Calderon-Montano JM, Koolmeister T, Reaper PM, Mortusewicz O, Jacques SA, Kuiper RV, Schultz N, Scobie M, Charlton PA, Pollard JR, Berglund UW, Altun M, Helleday T. Cancer-Specific Synthetic Lethality between ATR and CHK1 Kinase Activities. Cell Rep. 2016;14(2):298-309.

9. Berglund UW, Sanjiv K, Gad H, Kalderen C, Koolmeister T, Pham T, Gokturk C, Jafari R, Maddalo G, Seashore-Ludlow B, Chernobrovkin A, Manoilov A, Pateras IS, Rasti A, Jemth AS, Almlof I, Loseva O, Visnes T, Einarsdottir BO, Gaugaz FZ, Saleh A, Platzack B, Wallner OA, Vallin KSA, Henriksson M, Wakchaure P, Borhade S, Herr P, Kallberg Y, Baranczewski P, Homan EJ, Wiita E, Nagpal V, Meijer T, Schipper N, Rudd SG, Brautigam L, Lindqvist A, Filppula A, Lee TC, Artursson P, Nilsson JA, Gorgoulis VG, Lehtio J, Zubarev RA, Scobie M, Helleday T. Validation and development of MTH1 inhibitors for treatment of cancer. Ann Oncol. 2016;27(12):2275-83.

10. Xie S, Mortusewicz O, Ma HT, Herr P, Poon RRY, Helleday T, Qian CM. Timeless Interacts with PARP-1 to Promote Homologous Recombination Repair. Mol Cell. 2015;60(1):163-76.

11. Tarish FL, Schultz N, Tanoglidi A, Hamberg H, Letocha H, Karaszi K, Hamdy FC, Granfors T, Helleday T. Castration radiosensitizes prostate cancer tissue by impairing DNA double-strand break repair. Sci Transl Med. 2015;7(312).

12. Carter M, Jemth AS, Hagenkort A, Page BD, Gustafsson R, Griese JJ, Gad H, Valerie NC, Desroses M, Bostrom J, Warpman Berglund U, Helleday T, Stenmark P. Crystal structure, biochemical and cellular activities demonstrate separate functions of MTH1 and MTH2. Nat Commun. 2015;6:7871.

13. Huber KVM, Salah E, Radic B, Gridling M, Elkins JM, Stukalov A, Jemth AS, Gokturk C, Sanjiv K, Stromberg K, Pham T, Berglund UW, Colinge J, Bennett KL, Loizou JI, Helleday T, Knapp S, Superti-Furga G. Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy. Nature. 2014;508(7495):222-+.

14. Gad H, Koolmeister T, Jemth AS, Eshtad S, Jacques SA, Strom CE, Svensson LM, Schultz N, Lundback T, Einarsdottir BO, Saleh A, Gokturk C, Baranczewski P, Svensson R, Berntsson RPA, Gustafsson R, Stromberg K, Sanjiv K, Jacques-Cordonnier MC, Desroses M, Gustavsson AL, Olofsson R, Johansson F, Homan EJ, Loseva O, Brautigam L, Johansson L, Hoglund A, Hagenkort A, Pham T, Altun M, Gaugaz FZ, Vikingsson S, Evers B, Henriksson M, Vallin KSA, Wallner OA, Hammarstrom LGJ, Wiita E, Almlof I, Kalderen C, Axelsson H, Djureinovic T, Puigvert JC, Haggblad M, Jeppsson F, Martens U, Lundin C, Lundgren B, Granelli I, Jensen AJ, Artursson P, Nilsson JA, Stenmark P, Scobie M, Berglund UW, Helleday T. MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool. Nature. 2014;508(7495):215-+.

15. Costantino L, Sotiriou SK, Rantala JK, Magin S, Mladenov E, Helleday T, Haber JE, Iliakis G, Kallioniemi OP, Halazonetis TD. Break-Induced Replication Repair of Damaged Forks Induces Genomic Duplications in Human Cells. Science. 2014;343(6166):88-91.

16. Burrell RA, McClelland SE, Endesfelder D, Groth P, Weller MC, Shaikh N, Domingo E, Kanu N, Dewhurst SM, Gronroos E, Chew SK, Rowan AJ, Schenk A, Sheffer M, Howell M, Kschischo M, Behrens A, Helleday T, Bartek J, Tomlinson IR, Swanton C. Replication stress links structural and numerical cancer chromosomal instability. Nature. 2013;494(7438):492-6.

17. Moskwa P, Buffa FM, Pan YF, Panchakshari R, Gottipati P, Muschel RJ, Beech J, Kulshrestha R, Abdelmohsen K, Weinstock DM, Gorospe M, Harris AL, Helleday T, Chowdhury D. miR-182-Mediated Downregulation of BRCA1 Impacts DNA Repair and Sensitivity to PARP Inhibitors. Mol Cell. 2011;41(2):210-20.

18. Petermann E, Orta ML, Issaeva N, Schultz N, Helleday T. Hydroxyurea-Stalled Replication Forks Become Progressively Inactivated and Require Two Different RAD51-Mediated Pathways for Restart and Repair. Mol Cell. 2010;37(4):492-502.

19. Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, Kyle S, Meuth M, Curtin NJ, Helleday T. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434(7035):913-7.

For a full list of publications please visit myPublications