Jo Waaler

Group Leader
Image of Jo Waaler
Mobile phone 95148669
Room Domus Medica IV
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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:

  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. 

 

Publications

  1. Jo Waaler et al. Tankyrase inhibition sensitizes melanoma to PD-1 immune checkpoint blockade in syngeneic mouse models. Preprint BioRxiv doi:https://doi.org/10.1101/526343 (under revision 2018)
  2. Anumala UR, Waaler J, Nkizinkiko Y, Ignatev A, Lazarow K, Lindemann P, Olsen PA, Murthy S, Obaji E, Majouga AG, Leonov SV, von Kries JP, Lehtiö L, Krauss S*, Nazaré M*. (*Shared last authorship) (2017) Discovery of a Novel Series of Tankyrase Inhibitors by a Hybridization Approach. Journal of Medicinal Chemistry. 2017 Nov 20.
  3. Solberg, NT, Waaler J, Lund K, Mygland L, Olsen PA, Krauss S. Tankyrase Inhibition Enhances the Antiproliferative Effect of PI3K and EGFR Inhibition, Mutually Affecting b-Catenin and Akt Signaling in Colorectal Cancer. Molecular Cancer Research 16, no. 3 (2018): 543-553.
  4. Voronkov A*, Holsworth DD*, Waaler J*, Wilson SR, Ekblad B, Perdreau-Dahl H, Dinh H, Drewes G, Hopf C, Morth JP, Krauss S (2013) Structural basis and SAR for G007-LK, a lead stage 1,2,4-triazole based specific Tankyrase 1/2 inhibitor. Journal of Medicinal Chemistry, (2013) 56 (7), 3012-23. *Shared first authorship.
  5. Lau T, Chan E, Callow M, Waaler J, Boggs J, Blake RA, Magnuson S, Sambrone A, Schutten M, Firestein R, Machon O, Korinek V, Choo E, Diaz D, Merchant M, Polakis P, Holsworth DD, Krauss S, Costa M . A novel tankyrase small-molecule inhibitor suppresses APC mutation-driven colorectal tumor growth Cancer Research, (2013), 73 (10), 3132-44.
  6. Waaler J, Machon O, Tumova L, Dinh H, Korinek V, Wilson SR, Paulsen JE, Pedersen NM, Eide TJ, Machonova O, Gradl D, Voronkov A, von Kries JP, Krauss S (2012) A novel tankyrase inhibitor decreases canonical Wnt signaling in colon carcinoma cells and reduces tumor growth in conditional APC mutant mice. Cancer Res, 72 (11), 2822-32

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Published Mar. 22, 2019 2:54 PM - Last modified May 3, 2021 11:25 AM

Research groups