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
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