Chemical Biology & Therapeutics
Despite tremendous progress in developmental biology research over the past decade, it is still not well understood how developmental pathways orchestrate tissue regeneration from epithelial stem cells. Our group is focused on identifying signaling pathways, mechanisms and molecules regulating tissue stem cell activation and differentiation. The liver is well known for its unique potential to regenerate. We therefore study liver regeneration in mice and man to identify global players of regeneration and translate our findings into other tissues and eventually into therapeutic concepts. Our group utilizes a variety of genetic, biochemical, and high-throughput technologies to identify molecules and mechanisms that regulate this process in mammals. Tissue stem cell lineage tracing allows tracing of cells during regeneration and the identification of novel stem cell markers. Gain- and loss-of-function mutants are analysed to get mechanistic insights into tissue stem cell regulation and differentiation. Organoid-based ex vivo assays and other cellular models are used to study developmental pathways in vitro. Collaborations with our high-throughput technology group enable us to perform large-scale pathway genetic screens that reveal novel targets within individual pathways. Academic collaborations with the University Hospital Basel further allow the study of developmental pathways in patient samples and validation of our findings in man. Ultimately, we aim to identify molecules and biologics with therapeutic potential in regenerative medicine to treat diseases with high unmet medical need.
AXIN2+ Pericentral Hepatocytes Have Limited Contributions to Liver Homeostasis and Regeneration.
Sun T, Pikiolek M, Orsini V, Bergling S, Holwerda S, Morelli L, Hoppe PS, Planas-Paz L, Yang Y, Ruffner H, Bouwmeester T, Lohmann F, Terracciano LM, Roma G, Cong F, Tchorz JS.
Cell Stem Cell. 2020 Jan 2;26(1):97-107
YAP, but Not RSPO-LGR4/5, Signaling in Biliary Epithelial Cells Promotes a Ductular Reaction in Response to Liver Injury.
Planas-Paz L, Sun T, Pikiolek M, Cochran NR, Bergling S, Orsini V, Yang Z, Sigoillot F, Jetzer J, Syed M, Neri M, Schuierer S, Morelli L, Hoppe PS, Schwarzer W, Cobos CM, Alford JL, Zhang L, Cuttat R, Waldt A, Carballido-Perrig N, Nigsch F, Kinzel B, Nicholson TB, Yang Y, Mao X, Terracciano LM, Russ C, Reece-Hoyes JS, Gubser Keller C, Sailer AW, Bouwmeester T, Greenbaum LE, Lugus JJ, Cong F, McAllister G, Hoffman GR, Roma G, Tchorz JS.
Cell Stem Cell. 2019 Jul 3;25(1):39-53
The RSPO–LGR4/5–ZNRF3/RNF43 module controls liver zonation and size.
Planas-Paz L, Orsini V, Boulter L, Calabrese D, Pikiolek M, Nigsch F, Xie Y, Roma G, Donovan A, Marti P, Beckmann N, Dill MT, Carbone W, Bergling S, Isken A, Mueller M, Kinzel B, Yang Y, Mao X, Nicholson TB, Zamponi R, Capodieci P, Valdez R, Rivera D, Loew A, Ukomadu C, Terracciano LM, Bouwmeester T, Cong F, Heim MH, Forbes SJ, Ruffner H, Tchorz JS.
Nat Cell Biol. 2016 May;18(5):467-79.
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