Thomas Helleday


Thomas Helleday
Translational Medicine and Chemical Biology
Karolinska Institutet

Research interests

Many DNA damaging anti-cancer drugs cause replication-associated DNA damage that kill cancer cells. This is an effective way of treating cancer, but the problem is that also normal cells are damaged. Our strategy is to exploit the high level of DNA damage in cancer cells and prevent the repair of these lesions. Using DNA repair inhibitors, we can selectively introduce toxic DNA damage to cancer cells.

Our idea is based on three strategies:

1) Basic science understanding on DNA replication repair.
Basically all potentially curative anti-cancer treatments work by causing DNA damage. This damage is normally not lethal but is converted into lethal lesions upon DNA replication. Cancer cells have numerous co-ordinated DNA repair pathways operating in replicating cells and our strategy is to gain in depth knowledge into these processes, giving us insights into how genome stability is maintained and also identifying putative targets for anti-cancer treatment.

2) DNA repair pathways operating in cancer patients.
It is critical that we work closely with patients and investigate if DNA repair pathways identified in basic science are operating in cancer specimen and what their roles are in this context. Therefore, we conduct our experiments in collaboration with cancer patients, to see which DNA repair pathways are relevant in their individual cancers.

3) Small molecule inhibitors to selectively kill cancer cells.
Once we gain understanding of repair processes in cancer we purify putative DNA repair proteins and identify small molecule inhibitors. These are further improved to effectively and selectively inhibit the protein in cells. Ultimately, we progress these small molecules and test in cancer patients in clinical trials to determine if we are able to improve current anti-cancer treatments.

Group members

Adam Throup PostDoc
Amanda Jensen Student
Ann-Sofie Jemth Scientist
Armando Cazares-Körner PostDoc
Azita Rasti Scientist
Bishoy Hanna Student
Brent Page PostDoc
Camilla Gokturk Scientist
Camilla Sjögren Administrator
Christina Kalderén Scientist
Cindy Körner PostDoc
Cynthia Paulin PostDoc
Daniel Solvie Master student
Elisee Wiita Scientist
Evert Homan Scientist
Firas Al-Ubaidi Scientist
Flor Pineiro Lab Assistant
Helge Gad Scientist
Ingrid Almlöf Scientist
Judith Unterlass Postdoc
Karl Vallin Scientist
Kristina Edfeldt Research Manager
Kumar Sanjiv Scientist
Lars Bräutigam Scientist
Linda Pudelko PhD Student
Marianna Tampere PhD Student
Marjo Puumalainen PostDoc
Martin Henriksson Scientist
Martin Scobie Scientist
Matthieu Desroses Scientist
Mingqiu Hu Visiting researcher
Molly Lightowler Student
Nadilly Bonagas Student
Nicholas Valerie PhD Student
Niklas Schultz Scientist
Nina Gustavsson Sheppard PostDoc
Nuno Amaral PostDoc
Olga Loseva Scientist
Oliver Mortusewicz Scientist
Olov Wallner Scientist
Patrick Herr PostDoc
Pawel Baranczewski Scientist
Prasad Wakchaure postDoc
Roland Fiskesund PostDoc
Rosa Pennisi Student
Ruth Moulson Chemistry student
Sabin Llona-Minguez Scientist
Sabina Eriksson Lab Manager
Saeed Eshtad PhD Student
Sanjay Borhade postDoc
Sean Rudd PostDoc
Sofia Henriksson PostDoc
Stella Karsten PhD Student
Sun Lee Master student
Teresa Sandvall Scientist
Therese Pham Scientist
Thomas Helleday Professor
Tobias Koolmeister Scientist
Torkild Visnes PostDoc
Tove Bekkhus Master student
Ulrika Warpman Berglund Scientist
Vibhu Vibhu PostDoc
XiangWei Hua Visiting researcher

 

Key publications

  • 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) Targeting MTH1 nucleotide triphosphatase prevents sanitation of oxidised dNTP pools and kills cancer cells Nature. in press.
  • 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 IP, Swanton C. (2013) Replication stress links structural and numerical cancer chromosomal instability. Nature 494(7438):492-6.
  • Petermann E, Woodcock M, Helleday T (2010) Chk1 promotes replication fork progression by controlling replication initiation. Proc Natl Acad Sci USA, 107:16090-5.
  • 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.
  • Moskwa P, Buffa FM, Pan Y, Panchakshari R, Vischioni B, Parker A, Pezzella F,   Gottipati P, Abdelmohsen K, Camps C, Ragoussis J, Kulshrestha R, Weinstock DM,  Sharma RA, Gorospe M, Harris AL, Helleday T* and Chowdhury D* (2011)  miR-182-mediated down-regulation of BRCA1 impacts on the DNA damage response and breast cancer therapy. Molecular Cell, 41:210-20. * co-corresponding author

External homepage

www.helleday.org

Contact

thomas.helleday@scilifelab.se

More contact information

http://ki.se/en/people/thohel