Jo Waaler

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

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

  • Kierulf-Vieira, Kirsten Strømme; Sandberg, Cecilie; Waaler, Jo; Lund, Kaja; Skaga, Erlend; Saberniak, Birthe Mikkelsen; Panagopoulos, Ioannis; Brandal, Petter; Krauss, Stefan; Langmoen, Iver Arne & Vik-Mo, Einar O. (2020). A small-molecule tankyrase inhibitor reduces glioma stem cell proliferation and sphere formation. Cancers.  ISSN 2072-6694.  12(6), s 1- 16 . doi: 10.3390/cancers12061630 Full text in Research Archive.
  • Waaler, Jo; Leenders, Ruben G G; Sowa, Sven T.; Mahmuda, Shoshy; Lycke, Eric Maximilian; Nieczypor, Piotr; Aertssen, Sjoerd; Murthy, Sudarshan; Galera-Prat, Albert; Damen, Eddy; Wegert, Anita; Nazaré, Marc; Lehtiö, Lari & Krauss, Stefan (2020). Preclinical lead optimization of a 1,2,4-triazole based tankyrase inhibitor. Journal of Medicinal Chemistry.  ISSN 0022-2623.  63(13), s 6834- 6846 . doi: 10.1021/acs.jmedchem.0c00208 Full text in Research Archive.
  • Waaler, Jo; Mygland, Line; Tveita, Anders Aune; Strand, Martin Frank; Solberg, Nina; Olsen, Petter Angell; Aizenshtadt, Aleksandra; Fauskanger, Marte; Lund, Kaja; Mahmuda, Shoshy (Brinch, Shoshy Alam); Lycke, Eric Maximilian; Dybing, Elisabeth; Nygaard, Vegard; Bøe, Sigurd; Heintz, Karen Marie; Hovig, Eivind; Hammarström, Clara Louise; Corthay, Alexandre & Krauss, Stefan (2020). Tankyrase inhibition sensitizes melanoma to PD-1 immune checkpoint blockade in syngeneic mouse models. Communications Biology.  ISSN 2399-3642.  3 . doi: 10.1038/s42003-020-0916-2 Full text in Research Archive.
  • Wang, Hong; Kuusela, Sara; Rinnankoski-Tuikka, Rita; Dumont, Vincent; Bouslama, Rim; Ramadan, Usama Abo; Waaler, Jo; Linden, Anni-Maija; Chi, Nai-Wen; Krauss, Stefan; Pirinen, Eija & Lehtonen, Sanna (2020). Tankyrase inhibition ameliorates lipid disorder via suppression of PGC-1α PARylation in db/db mice. International Journal of Obesity.  ISSN 0307-0565.  44(8), s 1691- 1702 . doi: 10.1038/s41366-020-0573-z
  • Lien, Vegard Torp; Kristiansen, Margrethe Konstanse; Pettersen, Solveig; Haugen, Mads Haugland; Olberg, Dag Erlend; Waaler, Jo & Klaveness, Jo (2019). Towards dual inhibitors of the MET kinase and WNT signaling pathway; design, synthesis and biological evaluation. RSC Advances.  ISSN 2046-2069.  9(63), s 37092- 37100 . doi: 10.1039/c9ra08954c
  • Norum, Jens Henrik; Skarpen, Ellen; Brech, Andreas; Kuiper, Raoul; Waaler, Jo; Krauss, Stefan & Sørlie, Therese (2018). The tankyrase inhibitor G007-LK inhibits small intestine LGR5+ stem cell proliferation without altering tissue morphology. Biological Research (Print).  ISSN 0716-9760.  51(1) . doi: 10.1186/s40659-017-0151-6 Full text in Research Archive.
  • Solberg, Nina Therese; Waaler, Jo; Iversen, Kaja Lund; Mygland, Line; Olsen, Peter Angell & Krauss, Stefan (2018). TANKYRASE Inhibition Enhances the Antiproliferative Effect of PI3K and EGFR Inhibition, Mutually Affecting β-CATENIN and AKT Signaling in Colorectal Cancer. Molecular Cancer Research.  ISSN 1541-7786.  16(3), s 1541 . doi: 10.1158/1541-7786.MCR-17-0362
  • Anumala, Upendra Rao; Waaler, Jo; Nkizinkiko, Yves; Ignatev, Alexander; Lazarow, Katina; Lindemann, Peter; Olsen, Petter Angell; Murthy, Sudarshan; Obaji, Ezeogo; Majouga, Alexander G; Leonov, Sergey; von Kries, Jens Peter; Lehtiö, Lari; Krauss, Stefan & Nazare, Marc (2017). Discovery of a Novel Series of Tankyrase Inhibitors by a Hybridization Approach. Journal of Medicinal Chemistry.  ISSN 0022-2623.  60(24), s 10013- 10025 . doi: 10.1021/acs.jmedchem.7b00883
  • Solberg, Nina T.; Waaler, Jo; Lund, Kaja; Mygland, Line; Olsen, Petter A. & Krauss, Stefan (2017). TANKYRASE inhibition enhances the antiproliferative effect of PI3K and EGFR inhibition, mutually affecting β-CATENIN and AKT signaling in colorectal cancer. Molecular Cancer Research.  ISSN 1541-7786.  16(3), s 543- 553 . doi: 10.1158/1541-7786.MCR-17-0362
  • Vehus, Tore; Waaler, Jo; Krauss, Stefan; Lundanes, Elsa & Wilson, Steven Ray Haakon (2017). Combining HIC, SEC, and IEX with Fluorescence Polarization for Drug Target Discovery. LC GC North America.  ISSN 1527-5949.  30(5), s 232- 239 Full text in Research Archive.
  • Haikarainen, Teemu; Waaler, Jo; Ignatev, Alexander; Nkizinkiko, Yves; Venkannagaria, Harikanth; Obaji, Ezeogo; Krauss, Stefan & Lehtiö, Lari (2016). Development and structural analysis of adenosine site binding tankyrase inhibitors. Bioorganic & Medicinal Chemistry Letters.  ISSN 0960-894X.  26(2), s 328- 333 . doi: 10.1016/j.bmcl.2015.12.018
  • Vehus, Tore; Røberg-Larsen, Hanne; Waaler, Jo; Aslaksen, Sigrid; Krauss, Stefan; Wilson, Steven Ray Haakon & Lundanes, Elsa (2016). Versatile, sensitive liquid chromatography mass spectrometry–Implementation of 10 μm OT columns suitable for small molecules, peptides and proteins. Scientific Reports.  ISSN 2045-2322.  6 . doi: 10.1038/srep37507 Full text in Research Archive.
  • Thorvaldsen, Tor Espen; Pedersen, Nina Marie; Wenzel, Eva; Schultz, Sebastian; Brech, Andreas; Liestøl, Knut; Waaler, Jo; Krauss, Stefan & Stenmark, Harald Alfred (2015). Structure, dynamics, and functionality of tankyrase inhibitor-induced degradasomes. Molecular Cancer Research.  ISSN 1541-7786.  13(11), s 1487- 1501 . doi: 10.1158/1541-7786.MCR-15-0125
  • Zhong, Linlin; Ding, Yun; Bandyopadhyay, Gautam; Waaler, Jo; Börgeson, Emma; Smith, Susan; Zhang, Mingchen; Phillips, Susan A.; Mahooti, Sepi; Mahata, Sushil K.; Shao, Jianhua; Krauss, Stefan & Chi, Nai-Wen (2015). The PARsylation activity of tankyrase in adipose tissue modulates systemic glucose metabolism in mice. Diabetologia.  ISSN 0012-186X.  59(3), s 582- 591 . doi: 10.1007/s00125-015-3815-1
  • Stratford, Eva Wessel; Daffinrud, Jeanette L.; Munthe, Else; Castro, Russell; Waaler, Jo; Krauss, Stefan & Myklebost, Ola (2014). The tankyrase-specific inhibitor JW74 affects cell cycle progression and induces apoptosis and differentiation in osteosarcoma cell lines. Cancer Medicine.  ISSN 2045-7634.  3(1), s 36- 46 . doi: 10.1002/cam4.170
  • Lau, Ted; Chan, Emily; Callow, Marinella; Waaler, Jo; Boggs, Jason; Blake, Robert A.; Magnuson, Steven; Sambrone, Amy; Schutten, Melissa; Firestein, Ron; Machon, Ondrej; Korinek, Vladimir; Choo, Edna; Diaz, Dolores; Merchant, Mark; Polakis, Paul; Holsworth, Daniel D.; Krauss, Stefan & Costa, Mike (2013). A Novel Tankyrase Small-Molecule Inhibitor Suppresses APC Mutation-Driven Colorectal Tumor Growth. Cancer Research.  ISSN 0008-5472.  73(10), s 3132- 3144 . doi: 10.1158/0008-5472.CAN-12-4562
  • Voronkov, Andrey; Holsworth, Daniel D.; Waaler, Jo; Wilson, Steven Ray Haakon; Ekblad, Bie; Perdreau, Harmonie; Dinh, Huyen Mong Thi; Drewes, Gerard; Hopf, Carsten; Morth, Jens Preben & Krauss, Stefan (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.  ISSN 0022-2623.  56(7), s 3012- 3023 . doi: 10.1021/jm4000566
  • Waaler, Jo; Machon, Ondrej; Tumova, Lucie; Dinh, Huyen Mong Thi; Korinek, Vladimir; Wilson, Steven Ray Haakon; Paulsen, Jan Erik; Pedersen, Nina Marie; Eide, Tor Jacob; Machonova, Olga; Gradl, Dietmar; Voronkov, Andrey; von Kries, Jens Peter & Krauss, Stefan (2012). A novel tankyrase Inhibitor decreases canonical Wnt signaling in colon carcinoma cells and reduces tumor growth in conditional APC mutant mice. Cancer Research.  ISSN 0008-5472.  72(11), s 2822- 2832 . doi: 10.1158/0008-5472.CAN-11-3336
  • Waaler, Jo; Machon, Ondrej; von Kries, Jens Petter; Wilson, Steven Ray Haakon; Lundanes, Elsa; Wedlich, Doris; Gradl, Dietmar; Paulsen, Jan Erik; Machonova, Olga; Dembinski, Jennifer; Dinh, Huyen Mong Thi & Krauss, Stefan (2011). Novel Synthetic Antagonists of Canonical Wnt Signaling Inhibit Colorectal Cancer Cell Growth. Cancer Research.  ISSN 0008-5472.  71(1), s 197- 205 . doi: 10.1158/0008-5472.CAN-10-1282

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

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