Research in our laboratory is focused on:
a. The impact of genome instability on pathways associated with longevity, aging and age-related pathology: We aim to identify common genome-wide expression patterns between a number of TCR-defective, progeroid mice and mice that carry (tissue-specific) constitutive defects in transcription. We are using a number of advanced molecular, genomics and imaging approaches to investigate the role of transcriptional instability in progeria and age-related pathology.
b. The impact of progeroid mutations on tumour development: we aim at investigating the fine balance between cancer protection and accelerated aging. This approach might provide us both with mechanistic insight into the complex process of tumorigenesis as well as gene targets for its experimental modulation in the future.
c. Genome instability and tissue-specific progeria: we are focusing at investigating age-related processes driven by genome instability in a tissue-specific manner using the loxP/ Cre recombinase technology to restrict DNA repair deficiency in a single type of tissue while leaving the remaining part of the organism intact.
d. Development of advanced bioinformatics approaches to integrate functional genomics data with and biological endpoints in cancer and aging.

Selected Publications

Garinis GA, Uittenboogaard LM, van IJcken W, Breit TM, van Steeg H, Mullenders LHF, van der Horst GTJ, Hoeijmakers JHJ and Schumacher B (2009) Persistent transcription-blocking DNA lesions trigger somatic growth attenuation associated with longevity. Nature Cell Biology 11: 604-15.

Garinis GA, Gijsbertus van der Horst, Hoeijmakers JH (2008) DNA damage and aging: new-age ideas for an age-old problem. Nature Cell Biology 10: 1241-7.

Schumacher B, van der Pluijm I, Moorhouse MJ, Rasile Robinson A, Suh Y, Breit TM, van Steeg H, Niedernhofer LJ, van Ijcken W, Bartke A, Spindler SR, Hoeijmakers JHJ, van der Horst GTJ and Garinis GA (2008) Delayed and accelerated aging share common longevity assurance mechanisms. PLoS Genet 15: 1000161.

van der Pluijm I, Garinis GA, Brandt RMC, Gorgels TGMF, Wijnhoven SW, Diderich KEM, Mitchell JR, van Oostrom C, Beems R, Niedernhofer LJ, Velasco S, Friedberg EC, Tanaka K, van Steeg H, Hoeijmakers JHJ and van der Horst GTJ (2006) Impaired Genome Maintenance Suppresses the GH/IGF1 Axis in Cockayne Syndrome Mice. PLoS Biol 12;5(1):e2.

Niedernhofer LJ, Garinis GA, Raams A, Appeldoorn E, Lalai AS, Odijk H, Oostendorp R, Ahmad A, Robinson AR, Nair P, Calder R. Brent, van Leeuwen W, Theil AF, Vermeulen W, van der Horst GTJ, Meinecke P, Kleijer WJ, Vijg J, Jaspers NGJ, Hoeijmakers JHJ (2006) A New Progeria Links the DNA Damage Response with Life Span Regulators. Nature 444: 1038-43.