Waaler lab, Department of Immunology, Oslo University Hospital
The Cell Signaling and Drug Discovery research group is located at the Department of Immunology (IMM) at Oslo University Hospital – Rikshospitalet and is led by Group Leader Jo Waaler www.ous-research.no/waaler. The group will consist of 2-3 postdocs and 2-3 technicians along with Master's students. The research group is also associated with the RCN Centre of Excellence (SFF) - Hybrid Technology Hub - Centre for Organ on a Chip-Technology: www.med.uio.no/hth/english. Jo Waaler has functioned as a supervisor for 11 Master’s students.
Background
The research group focuses on tankyrase 1 and tankyrase 2 (TNKS1/2), enzymes from the PARP family that regulate protein activity, interactions, and degradation through mono- or poly-ADP-ribosylation and downstream cell signaling. TNKS1/2 proteins are key players in the regulation of WNT/β-catenin and Hippo signaling pathways, which are implicated in various diseases, including cancer, immune evasion and fibrosis. Consequently, significant efforts have been dedicated to developing selective TNKS1/2 inhibitors.
Oslo University Hospital has established itself as a leading center for chemical biology and has developed a small-molecule TNKS inhibitor program. These inhibitors modulate several target proteins, such as AXIN1 and AXIN2 in the β-catenin destruction complex, thereby inhibiting WNT/β-catenin signaling, and AMOT proteins in the Hippo signaling pathway, leading to YAP signaling inhibition.
40-65% of melanoma patients do not respond to immune checkpoint inhibitor (ICPi) therapy. Resistance mechanisms are currently being mapped, and cellular signaling pathways, such as YAP and WNT/β-catenin signaling, emerge as promising targets for therapeutical intervention. β-catenin is the key transcriptional regulator of WNT/β-catenin signaling, and β-catenin-induced immune evasion is found in