Research topic 1: The oncogenic function of MYC
Almost all human tumors express significantly more MYC protein than healthy tissue, and mouse models have shown a clear relationship between MYC activity and the development of cancer. Thus, although MYC is a crucial oncogene, for many years MYC was not considered a promising therapeutic target because the MYC protein is also essential for healthy cells. With the motivation to find out whether and how the oncogenic function of MYC differs from its physiological mode of action, I have intensively investigated the mechanism of MYC-mediated gene regulation in recent years and been able to make two fundamental observations.
First, we were able to show that MYC is a universal transcription factor that binds to the promoters of all expressed genes and can regulate them (Walz et al, Nature, 2014). Secondly, we found that the target genes differ significantly in their affinity for MYC (Lorenzin et al, eLife, 2016). High affinity target genes are regulated at low MYC concentrations, as is the case in healthy cells, and are important for cell growth and proliferation. At very high MYC levels, as found in tumor cells, MYC also binds to low affinity promoters and this binding leads to the regulation of genes that mediate tumor-specific processes (Vo*, Wolf*, et al, Cancer Cell, 2016). In the future, we want to identify the target genes of MYC that mediate its oncogenic properties and attack them pharmaceutically.