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.

Our translational research aims to achieve the following objectives:

Main objectives:

1. Identify TNKS-dependent diseases with high unmet medical needs, assess the effectiveness of TNKS inhibition, explore potential therapeutic applications, and investigate the underlying mechanisms of its treatment effects.
2. Develop treatments for human use by advancing our preclinical drug candidate toward clinical trials, supported by the company Odin Therapeutics, and progressing toward clinical testing.

Sub-objectives:

1. Investigate the effects and mechanisms of TNKS inhibition, both as a monotherapy and in combination therapies, on signaling pathways in cancer using cell culture and animal models.
2. Examine how TNKS inhibition enhances sensitivity to metastatic melanoma immunotherapy in immune-competent mouse models.
3. Assess the anti-fibrotic effects of TNKS inhibition in lung fibrosis using advanced methodologies, including cell culture, patient-derived samples, and animal models.
4. Explore the impact of TNKS inhibition on anti-viral responses in mouse models and cell cultures.

The research group is also associated with the RCN Centre of Excellence (SFF) - Hybrid Technology Hub - Centre for Organ on a Chip-Technology: https://www.med.uio.no/hth/english/.