Human Genetics 2 - Genome Instability and Cancer

Genome-caretaking mechanisms counteract the deleterious effects of DNA damage and are essential to prevent toxicity, mutations, genome instability, ageing and disease. Inborn defects in genes controlling genome stability underlie inherited cancer predisposition and neurodegeneration whereas somatic loss of genome stability drives sporadic cancer, and is associated with ageing. Tumours with defects in DNA damage repair mechanisms may be candidates for immunotherapy and other molecular therapeutics specifically targeting these defects.

The main aims of our research program are:

• To obtain mechanistic understanding of genome surveillance mechanisms.
• To elucidate how such mechanisms act to prevent pathologies.
• To improve diagnosis of pathologies caused by impaired genome surveillance mechanisms.
• To identify biomarkers of susceptibility to DNA damage to improve personalised cancer therapy.
• To exploit opportunities for prevention and personalized treatment of cancer, with a focus on hereditary and sporadic colorectal, breast and ovarian cancer and head/neck paragangliomas.
• To unveil roles of DNA damage and antibody effector pathways in inflammation.

The program encompasses basic as well as patient-oriented (translational) research and includes the use of various model systems (such as yeast, worms, mice and mammalian cell culture), and state-of-the-art technologies (e.g. next generation sequence technologies, genome- and proteome-wide screens). In addition, functional assays are being used and developed to assess pathogenicity of DNA variants in cancer-associated genes, and/or to predict outcomes of treatment.