We want to understand the pathobiology of ageing and cancer. Interestingly both processes are caused by DNA damage but with different outcomes. In aged cells, accumulation of DNA double strand breaks results in the activation of proteins that cause a cell cycle arrest thereby preventing the efficient regeneration of damaged tissues. Remarkably these cell cycle-regulating proteins that induce ageing are often mutated in cancer cells. Loss of these so called tumor suppressor genes, such as Retinoblastoma (Rb) or p53, results in uncontrolled cell divisions and tumor formation.  Our research team wants to determine the molecular mechanism that causes ageing and cancer by study the functions of tumor suppressors and their direct downstream effectors, the E2F transcription factors. We use genetic modified mouse models to elucidate the contribution of p53, Rb and E2Fs in ageing and cancer of the liver.

Our long-term goal is to gain mechanistic insights to develop therapeutic strategies delaying ageing and suppressing cancer.  One promising avenue we are currently exploring is whether atypical E2Fs (E2F7 and E2F8) can be used to inhibit liver cancer, because we discovered that these atypical E2Fs function as very potent tumor suppressor proteins. A major obstacle in creating novel anticancer drugs is that many tumor suppressor genes are mutated and therefore cannot be reactivated to block cancer. However atypical E2Fs are very rarely mutated in cancer and therefore represent a novel and promising therapeutic target that be activated in cancer cells to inhibit cell divisions. 

Furthermore we have developed unique expertise in the pathological analysis of genetic modified animals, and established in 2010 the Dutch Molecular Pathology Center (DMPC), which collaborates worldwide with more than 50 different research groups or industry partners to analyze their transgenic animal models of human diseases. In 2016, we created a novel Single Cell Analysis Center (SCAC), which has the unique expertise and innovative equipment to isolate, image, select and analyze single cells for global genomic and transcriptomic alterations. This novel technology platform can be used to identify novel subsets of cell populations in normal or diseased tissues. Moreover it can be used to determine the heterogeneity within tumors or aged tissues.