Hein Te Riele

Throughout my career I have been intrigued by mechanisms underlying genetic variation and its benefits and detriments such as evolutionary adaptation and development of cancer. Research in my team is a perpetuated interaction between two topics: how do cells manage to incorporate or avoid changes in their genetic code and how can we use this knowledge to improve protocols for genetic engineering, an indispensable tool in molecular biology. In 1988 I joined the group of Anton Berns at the NKI after a solid training in bacterial genetics that turned out to be highly profitable for studying mechanisms of spontaneous or intended genetic variability in mammalian cells. Simply by adapting basic principles governing genetic exchange in bacteria, we rapidly managed to dramatically raise the efficiency of gene targeting in mouse embryonic stem cells (ESCs). Awarded with the AVL-Prize 1992 and appointed as junior PI at the NKI in 1993, I decided to focus on the mechanism that suppresses genetic exchange in ES cells: DNA mismatch repair (MMR). A lucky shot as that same year it was discovered that inherited defects in DNA MMR underlie the intestinal and endometrial cancer predisposition Lynch syndrome (LS). This interest indirectly laid the foundation for a new gene editing method we developed: oligonucleotide-mediated base substitution. A second research line of my team addresses an entirely different gene family, the retinoblastoma (Rb) genes. This brought us to another form of genomic instability: DNA breakage as a consequence of replication stress. Our current work is slowly turning towards clinical application of our insights in the different forms of genomic instability we encountered, which includes application of our gene modification technique in diagnostic oncology. To this aim we closely collaborate with clinical geneticists and gastroenterologists within and outside the NKI-AVL.

The Dutch Cancer Society (KWF) has been the main sponsor of my research, but also other sources of support, such as the Netherlands Organization for Scientific Research, have been instrumental, in particular to set up and develop fruitful collaborations within and outside the Netherlands. Throughout the years, I served as division head and member of the scientific advisory board and research council of the NKI-AVL. I am member of the Health Council of the Netherlands (since 2001), professor of Genetic instability and carcinogenesis at the VU University Amsterdam (since 2004) and dean of the Oncology Graduate School Amsterdam (as of 2014).