Cancers do not easily develop because cells command powerful mechanisms of tumor suppression. In the center of many of these mechanisms lies the p53 tumor suppressor protein. P53 is normally present in all somatic cells in small quantities. Numerous forms of stress, including lesions such as DNA damage and unwanted oncogene expression that might help transform a normal cell into a tumor cell, lead to a rise in p53 protein levels and an activation of p53 as a transcriptional regulator of genes and interaction partner of mitochondrial apoptosis-regulating proteins. As a result, damaged cells are forced to stop proliferating or die through apoptosis, depending on cell context, before becoming a tumor cell. Unfortunately, the p53 genes like all other genes can be subject to mutation, and mutated p53 may no longer be able to fullfil its task as a guardian of proper cell function. This opens up avenues for transformation, and indeed, there are hardly any known cancers with all p53-pathways fully intact. Moreover, the precise nature of the defects within the p53-pathways may be relevant for the response of a cancer to chemotherapy. My colleagues and I are primarily interested in the molecular mechanisms that i) underly gene regulation by p53, in particular in the context of the novel p53-interacting protein NIR co-discovered by us, ii) regulate the pro-apoptotic function of p53 at the mitochondria, and iii) lead to chemotherapy resistance upon mutation of p53. We have also been focusing on the mechanisms of genomic instability in cancers caused by the SCP1 cancer/testis antigen, the oncogenicity of the Np9 and Rec proteins encoded by human endogenous retrovirus (HERV) sequences, and the genetic variations in the human population that may predispose people to cancer and chronic inflammatory diseases.