Maja Köhn

New integrative approaches to study the roles of phosphatases in health and disease

Within intracellular signaling networks, protein phosphatases are counter players of kinases and play crucial roles in health and disease. In spite of their well-described involvement in diseases such as cancer, in general phosphatases are not being targeted directly in drug discovery efforts and in the clinic.

With the aim to understand phosphatase biology and to deliver new routes to make them targetable in therapy, my group works on different protein phosphatases with a role in disease. We develop chemical tools, mainly based on phosphatase substrates and interactors, to study the roles and molecular mechanisms of phosphatases. The tools are produced by peptide-, phosphoinositide and small molecule (solid phase) organic synthesis. We also investigate biological pathways and roles of specific phosphatases, namely the metastasis-promoting phosphatase PRL-3 and the ubiquitous phosphatase PP1, using biochemical and molecular cell biology approaches. Moreover, we have developed a fully searchable open access database on human active phosphatases and their protein and non-protein substrates (www.depod.org). Here, I will present an overview of our work with a focus on tool development and application for PP1 and PRL-3.