The PIDDosome in natural polyplodization

Caspases are a class of proteins that can cleave other proteins and are important in controlling tissue homeostasis by regulating the removal of no longer functional cells and by controlling inflammation. More recent studies suggest additional roles in cellular differentiation, including the formation and regeneration of skeletal muscle or the liver. These novel roles are often linked to caspase-dependent modulation of gene expression, such as those orchestrating the response to DNA damage or proliferation. This helps to maintain genome stability, while it can ensures the differentiation of cells that carry extra copies of our genetic information, such as those required for bone remodeling (osteoclasts) or heart contraction (cardiomyocytes). To understand the relevance of Caspase-2 and its interaction partners, as well as target proteins that it can cleave, for the maturation of osteoclasts and cardiomyocytes, we will exploit cell biology, Next Generation Sequencing and genetics to study biological programs initiated by the caspase-2-PIDDosome axis and the consequences of impaired function of this signaling process for bone remodeling and heart function. We believe our line of research has the potential to guide novel and innovative approaches to treat a range of different human pathologies including heart disease or osteoporosis.