Welcome to the homepage of Jo Waaler's research group: Cell Signaling and Drug Discovery

Jo WaalerGroup leader
Jo Waaler
Group leader

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, which is also connected to the centre of excellence - Hybrid Technology Hub (https://www.med.uio.no/hth/english/), has the following main research objectives:

  1. 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.
  2. 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.
  3. 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.