Understanding malignant tumors and developing efficient therapeutics. Normal cells regulate their life cycle and growth carefully, subordinating the Darwinian tendency to reproduce in favor of maintaining the homeostasis of the multicellular organism they inhabit. During evolution some cells in the human body undergo changes in their genetic material and become growth and survival dominant over the neighboring cells. More than 150 defined diseases known as malignant tumors develop as a consequence. This program breeds new ideas into the molecular understanding of different malignant tumors and the development of modern and more efficient therapeutics against these diseases.
The program focuses on the following topics:
- Ubiquitin and cancer – The program co-ordinated by Ivan Đikić will study signal transduction mediated by ubiquitin and Ub-like modifiers in tumor development.
- Ubiquitylation is an emerging mechanism implicated in a variety of non-proteolytic cellular functions. Ubiquitin (Ub) is a highly conserved protein of 8 kDa that becomes covalently attached to lysine residues of target proteins. Evidently, the types of Ub modifications that can form are diverse. The attachment of a single ubiquitin (Ub) or poly-Ub chains to proteins control gene transcription, DNA repair and replication, intracellular trafficking and virus budding. In these processes, protein ubiquitylation exhibits inducibility, reversibility and recognition by specialized domains, features similar to protein phosphorylation, which enable Ub to act as a signaling device.
- How different Ub and Ubl modifications, in particular monoUb, UbLys63 chains and SUMO, establish networks of protein-protein interactions and regulate cellular functions will be studied. Special focus will be on the molecular characterization of these processes during tumor development. Based on the accrued knowledge we plan to develop novel detection and therapeutic methods specific for different tumor types.