Mapping and Targeting of Oncoprotein Signaling Networks

Oncogenic signaling networks display a remarkable degree of plasticity. Despite only a limited number of alterations in oncogenes and tumor suppressor genes in most tumours, the majority of targeted anti-cancer therapeutics does not strongly improve the survival of cancer patients and suffers from the rapid development of resistance.

Work in my lab focuses on providing a detailed molecular understanding of how key oncoproteins reprogram cellular signaling networks and how targeted inhibitors perturb them. We use structural biology and protein biochemistry to understand the structure and regulation of key kinase oncoproteins at the molecular level, as well as state-of-the-are quantitative proteomics methods to map their cellular protein interaction- and phosphoproteome networks.

Our aim is to identify innovative and unconventional ways to selectively interfere with oncoprotein signaling with engineered proteins or small molecule inhibitors. Over the past years, we have established the use of small engineered antibody mimics, termed monobodies, to potently and selectively target intracellular protein-protein interactions of central oncoproteins. We are developing methods to deliver monobody proteins into tumor cells and to establish them as novel intracellular protein-based therapeutics.