Academic interests
The group performs research on the proteins tankyrase 1 and tankyrase 2 (TNKS1/2), members of the PARP family of enzymes that control protein activities, interactions and turn-over through mono- or poly-ADP-ribosylation as well as downstream cell signaling events. TNKS1/2 regulate a number of target proteins, including AXIN1 and AXIN2 (AXIN1/2) in the β-catenin destruction complex resulting in WNT/β-catenin signaling pathway inhibition, and AMOT proteins in the Hippo signaling pathway resulting in YAP signaling inhibition.
The group has the following main research objectives:
- We have established a tankyrase inhibitor (TNKSi) drug development program and have discovered highly potent small-molecule tankyrase inhibitors that block cancer -promoting WNT/β-catenin and YAP signaling activities. Comprehensive evaluation of effect in animal models as well as pharmacokinetics/ ADME testing and safety profiling is ongoing for our preclinical candidate-stage drugs aiming for early-stage clinical testing.
- To evaluate the effect and mechanism of action for TNKSi monotherapy and combination therapies in the regulation of signaling pathways in cancer using cell culture and mouse models.
- WNT/β-catenin signaling can play a central regulatory role in immune cell homeostasis, development and function as well as in peripheral T cell activation, differentiation and tumor cell -immune cell interplay. The objective is to assess the effect of and mechanism of action behind TNKSi/immune checkpoint inhibitor anti-cancer combination therapy as well as the involvement of the adaptive and innate immune system using isogenic mouse models.