The Krauss group
The Krauss group focuses on applying developmental biology and chemical biology to organ-on-a-chip technology.
The Krauss group has established a program for phenocopying spatial and temporal processes in the development of the embryonic liver, and in collaboration with Hanne Scholz for the embryonic pancreas in vitro. Using such processes, we aim to develop more structured organoids than hitherto possible and at the same time achieve better subsequent maturation and functionality. This is fundamental for a viable personalized drug testing platform. In parallel, we work towards standardizing adult human tissue for organ-on-a-chip integration and benchmarking. For testing the biological structures by various analytical and imaging platforms, we have established collaborations with the research groups of Hanne Scholz, Molly Stevens, Steven Wilson, Espen Mellum, Ørjan Martinsen and Philipp Häflinger. For components of the immune system, a collaboration with Aleksandre Corthay has been initiated.
The Krauss group together with Petter A. Olsen is also working on lineage reporters in iPS cells. The reporters provide tools for determining the activity of developmental signaling pathways in vitro, the differentiation status of organoids and the environmental signals such as sheer stress and oxygen levels. A focus is on WNT and hippo signaling reporters.
In the chemical biology program, the group has further advanced its Tankyrase inhibitor program with the lead compound OM-153 that has reached preclinical candidate status and is currently undergoing extensive toxicology tests. This program has led to a published patent (WO2019/243822), two articles that are currently in press in Communications Biology and one article that is under revision in the Journal of Medicinal Chemistry. The chemical biology program, which has received several supporting innovation grants, is closely coordinated with project leader Jo Waaler.
- 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. J Med Chem. 2017 Nov 20. doi: 10.1021/acs.jmedchem.7b00883. PMID: 29155568
- Zhong L, Ding Y, Bandyopadhyay G, Waaler J, Borgeson E, Smith S, Zhang M, Phillips S, Mahooti S, Mahata S, Shao S, Krauss S, Chi NW (2015) The PARsylation activity of tankyrase in adipose tissue modulates systemic glucose metabolism in mice. Diabetologia. 2016 Mar;59(3):582-91. doi: 10.1007/s00125-015-3815-1. Epub 2015 Dec 2. PMID: 26631215
- 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 J Med Chem, 56 (7), 3012-23. PMID: 23473363
- 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 (2013) A novel tankyrase small-molecule inhibitor suppresses APC mutation-driven colorectal tumor growth. Cancer Res, 73 (10), 3132-44. PMID: 23539443
- 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. PMID: 22440753