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Oncode Investigators Elzo de Wit and Ruben van Boxtel receive ERC Grant

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Oncode Institute is proud to announce that Oncode Investigators Elzo de Wit (Netherlands Cancer Institute) and Ruben van Boxtel (Princess Máxima Center) both receive the ERC Consolidator Grant. The ERC Consolidator Grants are awarded to outstanding researchers with at least seven and up to twelve years of experience after PhD, and a scientific track record showing great promise.

Oncode Institute is proud to announce that Oncode Investigators Elzo de Wit (Netherlands Cancer Institute) and Ruben van Boxtel (Princess Máxima Center) both receive the ERC Consolidator Grant. The ERC Consolidator Grants are awarded to outstanding researchers with at least seven and up to twelve years of experience after PhD, and a scientific track record showing great promise.

We asked both Investigators to comment on this news.

Ruben van Boxtel says: “The survival of children with cancer has increased tremendously during the last decades thanks to more intensive chemo- and radiotherapy treatment. For example, the survival of children with B-ALL, the most frequent childhood cancer, is currently over 90%. However, due to their lifesaving therapy, childhood cancer survivors can suffer from various health issues later in life, such as early aging, frailty and a high incidence of second novel cancers. In fact, second cancers are one of the major causes for long-term mortality in childhood cancer survivors. With the ERC grant, my team will investigate the molecular mechanisms underlying the initiation of therapy-related cancers. The goals of this research are to establish the damaging effects of chemotherapy in noncancerous normal tissues, to determine which components of the chemotherapy are most mutagenic and causative for the DNA mutations that drive the second cancer, and finally to identify predictive markers to distinguish children with an increased risk for developing a second cancer. Ultimately, this knowledge can be used to prevent the development of therapy-related second cancers in children who survived a first cancer.”

Ruben van Boxtel, photography by Marloes Verweij

Elzo de Wit says: “When stretched out, our genome measures over two meters, however it has to fit into a space, the cell nucleus, that is one-tenth the width of a human hair in diameter. This represents a tremendous storage challenge. My group studies the folding of the genome inside the nucleus. How the genome is folded is of crucial importance for a number of processes inside the nucleus, one of which is gene transcription. Different cells in our body transcribe different genes, this is what makes a liver cell a liver cell and a brain cell a brain cell. How exactly the folding of the genome contributes to the proper activation and silencing of genes is unknown.

With the ERC grant, we will induce rapid changes in the folding of the genome and measure how this influences transcription. This will enable us to better understand what drives changes in gene expression. A better understanding of the role of genome folding in gene expression will lead help to understand a range of diseases such as Cornelia de Lange syndrome, but also cancer in which genomic rearrangements influence the folding of the genome.

The Oncode base fund allows me to explore ‘untrodden paths’. This enables me to address fundamental research questions, some of which ended up in the ERC grant application. For instance, we developed cell lines, in which we can rapidly inactivate proteins. Because of the highly dynamic nature of genome organization, this is crucial for our research purposes. Before developing these tools it was not entirely certain which direction this research will go, however, they are crucial for furthering our understanding of gene regulation.”

Elzo de Wit, ©Netherlands Cancer Institute
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