Key publications

Michel M#, Benitez-Buelga C, Calvo PA, Hanna BMF, Mortusewicz O, Masuyer G, Davies J, Wallner O, Sanjiv K, Castañeda-Zegarra S, Jemth AS, Visnes T, Sastre-Perona A, Albers JJ, Danda AN, Homan EJ, Marimuthu K, Zhenjun Z, Chi CN, Sarno A, Wiita E, von Nicolai C, Komor A, Rajagopal V, Müller S, Hank EC, Varga M, Scaletti ER, Pandey M, Karsten S, Haslene-Hox H, Loevenich S, Marttila P, Rasti A, Mamonov K, Ortis F, Schömberg F, Loseva O, Stewart J, D’Arcy-Evans N, Koolmeister T, Henriksson M, Michel D, de Ory A, Acero L, Calvete O, Scobie M, Hertweck C, Vilotijevic I, Kalderén C, Osorio A, Perona R, Stolz A, Stenmark P, Warpman Berglund U, de Vega M,  Helleday T#. (2022). Small molecule activation of OGG1 increases base excision repair by gaining a new enzymatic function. Science. 376(6600):1471-1476.

 

Bonagas N, Gustafsson NMS, Henriksson M, Marttila P, Gustafsson R, Wiita E, Borhade S, Green AC, Vallin K, Sarno A, Svensson R, Göktürk C, Pham T, Jemth A-S, Loseva O, Cookson V, Kiweler N, Sandberg L, Rasti A, Unterlass JE, Haraldsson M, Andersson Y, Scaletti ER, Bengtsson C, Paulin CBJ, Sanjiv K, Abdurakhmanov E, Pudelko L, Kunz B, Desroses M, Iliev P, Färnegårdh K, Krämer A, Garg N, Michel M, Sahlberg SH, Jarvius M, Kalderén C, Bögedahl Jensen A, Almlöf I, Karsten S, Zhang SM, Häggblad M, Eriksson A, Liu J, Glinghammar B, Nekhotiaeva N, Klingegård F, Koolmeister T, Martens U, Llona-Minguez S, Moulson R, Nordström H, Parrow V, Dahllund L, Sjöberg B, Vargas IL, Vo DD, Wannberg J, Knapp S, Krokan HE, Arvidsson PI, Scobie M, Meiser J, Stenmark P, Warpman Berglund U, Homan EJ, Helleday T#. (2022). Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress. Nature Cancer. 3(2):156-172

 

Zhang SM, Desroses M, Hagenkort A, Valerie NCK, Rehling D, Carter M, Wallner O, Koolmeister T, Throup A, Jemth AS, Almlöf I, Loseva O, Lundbäck T, Axelsson H, Regmi S, Sarno A, Krämer A, Pudelko L, Bräutigam L, Rasti A, Göttmann M, Wiita E, Kutzner J, Schaller T, Kalderén C, Cázares-Körner A, Page BDG, Krimpenfort R, Eshtad S, Altun M, Rudd SG, Knapp S, Scobie M, Homan EJ, Berglund UW, Stenmark P, Helleday T#. (2020). Development of a chemical probe against NUDT15. Nat Chem Biol. 16(10):1120-1128

 

Warpman-Berglund U, Sanjiv K, Gad H, Kalderén C, Koolmeister T, Pham T, Gokturk C, Jafari R, Maddalo G, Seashore-Ludlow B, Chernobrovkin A, Manoilov A, Pateras IS, Rasti A, Jemth AS, Almlöf 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, Breutigham L, Lindqvist A, Filppula A, Lee T-C, Artursson P, Nilsson JA, Gorgoulis VG, Lehtiö J, Zubarov RA, Scobie M, Helleday T#. (2016). Validation and development of MTH1 inhibitors for the treatment of cancer. Ann.Oncol. 27(12):2275-2283

 

Tarish FL, Schultz N, Tanoglidi A, Hamberg H, Letocha H, Karaszi K, Hamdy FC, Granfors T, Helleday T#. (2015). Castration radiosensitizes prostate cancer tissue by impairing DNA double-strand break repair. Sci Transl Med.7(312):312re11

 

Gad H, Koolmeister T, Jemth A-S, Eshtad S, Jacques SA, Ström CE, Svensson LM, Einarsdottir B, Schultz N, Lundbäck T, Saleh A, Gokturk C, Baranczewski P, Svensson R, Strömberg K, Bräutigam L, Jacques-Cordonnier M-C, Desroses M, Gustavsson A-L, Berntsson RPA, Gustafsson R, Olofsson R, Vikingsson S, Johansson F, Loseva O, Sanjiv K, Johansson L, Höglund A, Hagenkort A, Pham T, Altun M, Gaugaz FZ, Evers B, Henriksson M, Vallin K, Wallner O,  Hammarström LGJ, Wiita E, Almlöf I, Axelsson H, Häggblad M, Jeppsson F, Martens U, Lundin C, Lundgren B, Granelli I, Jenmalm Jensen A, Artursson P, Nilsson JA, Stenmark P, Scobie M, Warpman Berglund U, Helleday T#. (2014). MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool. Nature. 508(7495):215-21

 

Petermann E, Orta L, Issaeva N, Schultz N and Helleday T#. (2010) Hydroxyurea-stalled replication forks become progressively inactivated and require two different RAD51- mediated pathways for restart and repair, Molecular Cell, 37, 492-502

 

Visnes T, Cázares-Körner 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, Kalderén C, Ba X, Zubarev RA, Stenmark P, Boldogh I, Helleday T#. (2018). Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation. Science. 362(6416):834-839

 

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

 

Sørensen CS, Hansen LT, Dziegielewski J, Syljuåsen RG, Lundin C, Bartek J#, Helleday T#. (2005). The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair. Nature Cell Biology.7(2); 195-201

Thomas Helleday

Research interests

The Helleday laboratory focuses on understanding the basic processes of DNA repair and nucleotide metabolism, translating original findings into novel treatments of cancer inflammation and virus infections. The strategy has for a long time been to have a multidisciplinary translational research group where basic scientists work alongside medicinal chemists, pharmacologists, drug developers as well as clinical trials experts. Staff working in the Helleday labs are all involved in the process from the early target discovery discussions all the way to phase II trials in patients. Our philosophy is that the people in the team is the main asset and that the input from all expertise contributes to sharpening the projects to increase the likelihood of success in our ultimate goal: to battle human diseases and improve lives.

The Helleday lab has been pioneering the DNA damage response (DDR) area over the last decades and demonstrated that homologous recombination defective cancers (HRD, e.g., BRCA mutant) are sensitive to PARP inhibitors (Bryant et al., 2005 Nature 434, 913-7), which was the first example of a synthetic lethal approach for treatment of cancer. This is rapidly becoming standard treatment for HRD positive cancer such as e.g., ovarian, breast, pancreatic, and prostate cancers. Several novel treatments are also emerging from the Helleday lab such as MTH1 inhibitors in cancer (Gad et al., 2014 Nature 508, 215-21) and OGG1 inhibitors in inflammation (Visnes et al., 2018 Science 362, 834-839) amongst others.

The Helleday lab has also been involved in pioneering several basic science discoveries such as oncogene-induced replication stress (Bartkova et al., 2006 Nature 444, 633-7) and uncovering repair and restart pathways at stalled replication forks (see for instance Sørensen et al., 2005 Nature Cell Biol 7, 195-201 or Petermann et al., 2010 Mol Cell 37, 492-502).

Research team

Research team Thomas Helleday – DNA repair and nucleotide metabolism

The research aims to i) purify and target proteins in DNA repair and metabolism, ii) use probes and genetic tools to increase basic knowledge around target proteins, and iii) translate basic research findings into new treatments tested in the clinic.

Group members

  • Ann-Sofie Jemth, Principal researcher and Team Leader Biochemistry and In Vitro Pharmacology
  • Athina Pliakou, Research coordinator
  • Elisee Wiita, Research engineer
  • Evert Homan, Senior research specialist
  • Helge Gad, Senior researcher
  • Ingrid Almlöf, Research engineer
  • Jianyu Shen, PhD student
  • Kumar Sanjiv, Principal researcher and Team Leader In Vivo Pharmacology
  • Maeve Long, postdoc
  • Mari Kullman Magnusson, Lab manager
  • Martin Henriksson, Research engineer
  • Martin Scobie, Research engineer
  • Maurice Michel, Assistant Professor and Lead Enzyme Catalysis
  • Niklas Schultz, Senior researcher
  • Oliver Mortusewicz, Principal researcher and Team Leader Basic Science
  • Olov Wallner, Research engineer and Team Leader Medicinal chemistry
  • Thomas Helleday, Professor, PI
  • Therese Pham, Research engineer
  • Viktoriia Tsuber, Research specialist

Contact

thomas.helleday@scilifelab.se

Last updated: 2024-01-15

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