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Hoeijmakers Group

Jan Hoeijmakers

Jan Hoeijmakers did his PhD (University of Amsterdam) on the very peculiar fishnet-like kinetoplast DNA of trypanosomes, which cause African sleeping sickness. In ‘spare’ time he discovered unexpected DNA rearrangements underlying antigenic variation which allows this parasite to evade immune destruction. Subsequently he started the molecular analysis of DNA repair in mammals at the Dept. of Molecular Genetics (Erasmus University Rotterdam) in 1981. He cloned the first and subsequently many other human DNA repair genes, allowing elucidation of DNA repair mechanisms and of the basis of human repair syndromes, such as the cancer-prone disorder xeroderma pigmentosum and the severe neurodevelopmental conditions Cockayne syndrome and trichothiodystrophy. His team pioneered DNA repair dynamics in living cells exploring novel imaging technologies, generated numerous mouse repair mutants, discovered a strong connection between accumulation of DNA damage and (accelerated) aging and a trade-off between cancer and aging. Importantly, the mouse mutants appeared superior models for Alzheimer’s disease addressing a tremendous unmet medical need. Accumulation of unrepaired DNA damage causing premature cell death and senescence also triggered an anti-aging ‘survival response’ which enhances maintenance at the expense of growth resembling the longevity response by dietary restriction. Remarkably, subjecting repair-deficient progeroid mice to actual dietary restriction tripled(!) their lifespan, drastically retarding DNA damage accumulation and accelerated aging most impressively neurodegeneration. These findings open perspectives for preventive interventions for healthy aging, reducing cancer and many aging-related diseases including neurodegeneration, and for therapy of human genome instability syndromes. For his work Jan Hoeijmakers received many prizes and awards, including the very prestigious 'Louis Jeantet' Prize for Medical Research in Europe for the entire work on DNA repair in 1995; the ‘Spinoza’ Prize, most recognized prize of the Dutch Science Organization in 1999; First awardee of the ‘Josephine Nefkens Prize’ for cancer research in 2001; ERC Advanced Grant DamAge in 2008 and a second ERC Advanced Grant Dam2Age in 2017; Royal distinction Knight in the Order of the Dutch Lion for important scientific achievements in the area of cancer and aging research in 2013; Invited for the Nobel-Forum lecture at the Karolinska Istitutet in 2016; and recipient of the very prestigious International Olav Thon Foundation personal Award in 2017.

Research

Damage to our genome occurs continuously in every cell at a massive scale. DNA damage leads to mutations that drive carcinogenesis or triggers cell death and senescence causing functional decline and aging. Our main research focus is the interplay between DNA damage accumulation and repair in cancer (therapy) and (accelerated) aging. By studying molecular mechanisms upto patients we intend to obtain an integral understanding and derive rational-based effective strategies, including nutritional and pharmacological interventions which promote overall healthy aging and reduce severe long term side effects and improve quality of life in children cured from cancer.

Key publications


1. Hoeijmakers, J.H.J. Genome maintenance mechanisms for preventing cancer. Nature 411, 366-374 (2001) (most cited paper in molec. sciences from Dutch scientist in 2000-2010).
2. de Boer, J., Andressoo, J.O., de Wit, J., Huijmans, J., Beems, R.B., van Steeg, H., Weeda, G., van der Horst, G.T.J., van Leeuwen, W., Themmen, A.P.N., Meradji, M. and Hoeijmakers, J.H.J. Premature aging in mice deficient in DNA repair and transcription. Science (research article), 296, 1276-1279 (2002). (see also Comments in Science, 296, 1250-1251, and in DNA Repair 2, 437-439).
3. Niedernhofer, L.J., Garinis, G.A., Raams, A., Lalai, S.A., Robinson, R.A., Appeldoorn, E., Odijk, H., Oostendorp, R., Ahmad, A., van Leeuwen, W., Theil, A., Vermeulen, W., van der Horst, G.T., Meinecke, P., Kleijer, W., Vijg, J., Jaspers, N.G.J., Hoeijmakers, J.H.J. A new progeriod syndrome reveals that genotoxic stress suppresses the somatotroph axis. Nature (research article) 444, 1038-1043 (2006). (see also accompanying ‘News and Views’ Nature by Kirkwood).
4. Marteijn, J.A., Lans, H., Vermeulen, W. and Hoeijmakers J.H.J. Understanding nucleotide excision repair and its roles in cancer and ageing. Nature Rev Mol Cell Biol: 15, 465-481 (2014).
5. Vermeij W.P., Dollé M.E.T., Reiling E., Jaarsma D., Payan-Gomez C, Bombardieri C.R., Wu H., Roks A.J.M., Botter S.M., van der Eerden B.C., Youssef S.A., Kuiper R.V., Nagarajah B., van Oostrom C.T., Brandt R.M.C., Barnhoorn S., Imholz S., Pennings J.L.A., de Bruin A., Gyenis Á., Pothof J, Vijg J, van Steeg H., and Hoeijmakers J.H.J. Restricted diet delays accelerated aging and genomic stress in DNA repair deficient mice. Nature (August, 24, 2016; p427-431, see also accompanying Nature ‘News and Views’ of Oshima and Martin, p316-317).

Group members

Jan Hoeijmakers (j.hoeijmakers@erasmusmc.nl), PI
Wilbert Vermeij (w.p.vermeij@prinsesmaximacentrum.nl), Post-doc
Willianne Vonk, Post-doc
Yvonne Rijksen, Technician
Winnie van den Boogaard, PhD-student

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