In the past decade mechanistic studies of gene regulation have been revolutionized by technological advances, but also by our improved understanding of epigenetic processes. It is now apparent that a higher order and complicated assembly of DNA, proteins and RNA, which is referred to as the architecture or “landscape” of chromatin is a critical determinant of gene expression. Thus in each cell exists a unique and complex status of “chromatin”.– This governs the accessibility of DNA sequences for transcriptional activators and other regulatory proteins which in turn determines the transcriptional program of each individual cell.
In particular, the ‘monarchs’ at the top of the hierarchy of chromatin remodelling and gene regulation need to be determined. Understanding the dynamics and reconfiguration of chromatin will allow us to compare human diseases with models in genetically engineered mice, in which we can test new therapeutic concepts. It is important to note that this ground breaking work meets ethical standards and 3R principles with respect to analysing patient samples and animal experimentation.
Our research focuses on cells of the immune system and cancer, where JAK/STAT signaling plays essential (patho)physiological roles. The chromatin landscape changes when immune cells differentiate to exert specialized functions, e.g. recognition and elimination of pathogens As chromatin modifiers and JAKs or STATs are dysregulated, i.e. mutated, hyperactivated or lost, in many different cancers, our mission is to discover how these pathological changes drive cancer and immune responses.