The Svedberg Award 2008
Thomas Helleday
Professor at Molecular Genetics at Stockholm University and
Cancer Therapeutics at the University of Oxford (UK).
A committee consisting of members from the SFBM and Swedish National
Committee for Molecular Biosciences boards has decided to propose Thomas
Helleday, to the The Svedberg award
2008 for his “Outstanding contributions to the
understanding of the molecular mechanisms of homologous recombination in
mammalian cells and their use for cancer treatment”. Helleday is affiliated
at the Department of Genetics, Microbiology and Toxicology, Stockholm
University and at the University of Oxford, UK.
The award of SEK 35 000 together with the medal and diploma was presented
at the annual meeting of SFBM 22-23 September 2008 in Göteborg.
Presentation of Helleday's research
My interest for cancer research was born when I, aged 16, work extra as nurse’s
assistant at a hematology unit at Danderyd’s hospital in Sweden. Patients died
like flies and were suffering from horrendous side effects of the cancer drugs.
This was my first encounter with death and I couldn’t bear it – I decided to
find a cure for cancer.
I started my Ph.D. project on genetic recombination in mammalian cells in
spring 1996, following my undergraduate degrees in Molecular Biology and
Business Administration and Economics (civilekonom), both from the Stockholm
University. One of the main findings in my thesis was that commonly used
brominated flame retardands induced gene rearrangements similar to those found
in cancer. This and other reports showing for instance that brominated flame
retardants accumulate in human breast milk resulted in a ban of brominated flame
retardants in Sweden.
Following my dissertation in 1999, I received my own grants that allowed me
to start up a small group in Stockholm. Realizing I needed to do a postdoc, I
joined the lab of Mark Meuth at the Institute for Cancer Studies, University of
Sheffield (UK). As I refused to listen or take orders as a postdoc, Mark Meuth
kindly offered me a lectureship in 2000 to develop my own ideas as a group
leader. From this time, I have split my time between my groups at the Stockholm
University and England.
The focus has been to understand how homologous recombination is used to
repair lesions that occur at stalled replication forks in mammalian cells. A
breakthrough came in 2005, when the group showed that PARP inhibitors
selectively kill BRCA2 defective tumours. The patent was licensed to KuDOS Ltd
(Cambridge) and today, PARP inhibitors are used world wide in clinical trials
for breast and ovarian cancers.
I have previously been awarded several prizes including, European Association
for Cancer Research Young Cancer Researchers Award 2007, The Royal Swedish
Academy of Sciences Hilda and Alfred Eriksson’s Prize 2007, British Association
for Cancer Research - AstraZeneca Young Scientist Frank Rose Award 2006, The
Eppendorf Young European Investigator Award 2005, European Environmental Mutagen
Society Young Scientist Award 2005.
Currently, I am a professor in Molecular Genetics at Stockholm University and
a professor in Cancer Therapeutics at the University of Oxford (UK). The lab in
Stockholm has 15 members and the Oxford lab 7 members.
Current Research
The primary goal of the Helleday labs is to exploit tumour defects for targeted
treatment of cancer. Virtually all cancers have a defect the DNA damage
response, by mutations in tumour suppressor genes. The defect in DNA damage
signalling or repair weakens the ability of the cancer cell to properly
replicate DNA, resulting in genetic instability that drives cancer progression.
In this project we uncover cancer specific signalling and repair pathways that
are targeted for novel anti-cancer treatments. The project involves
identification of DNA lesions formed during replication and characterisation of
DNA damage signalling and repair pathways activated by these lesions. The group
is engaged in understanding basic concepts of DNA damage signalling and repair
as well as conducting pre-clinical trials, to translate our basic discoveries to
the clinic.
Links:
http://www.rob.ox.ac.uk/research/researchgroups/thomas-helleday/
Selected recent references:
Gottipati, P., Cassel,. T.N., Savolainen, L., Helleday, T. (2008)
Transcription-associated recombination is dependent on replication in mammalian
cells. Molecular and Cellular Biology, 28(1):154-64.
Bartkova, J., et al. (2006) Oncogene-induced senescence is an integral part of the tumorigenesis barrier imposed by DNA damage checkpoints, Nature, 444(7119), 633-7.
Renglin Lindh, A., Rafii, S., Schultz, N., Cox, A., Helleday, T. (2006) Mitotic defects in XRCC3 variants T241M and D213N and their relation to cancer susceptibility, Human Molecular Genetics, 15(7), 1217-1224.
Bryant, H.E., Schultz, N, Thomas, H.D., Parker, K.M., Flower, D., Lopez, E., Kyle, S., Meuth, M., Curtin, N.J., Helleday, T. (2005) Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose)polymerase Nature, 434, 913-7.
El-Khamisy, S.F., Saifi, G.M., Weinfeld, M., Johansson, F., Helleday, T., Lupski, J.R., Caldecott, K.W. (2005) Defective DNA Single-Strand Break Repair in Spinocerebellar Ataxia with Axonal Neuropathy-1, Nature, 434, 108-13.
Sørensen, C.S., Hansen, L.T., Dziegielewski, J., Syljuåsen, R.G., 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.
Saleh-Gohari, N., Bryant, H.E., Schultz, N., Parker, K.M., Cassel, T.N., Helleday, T. (2005) Spontaneous homologous recombination is induced by collapsed replication forks that are caused by endogenous DNA single-strand breaks, Molecular and Cellular Biology, 25(16), 7158–7169