Chemical Biology & Therapeutics
Our group focuses on mechanisms of tissue and organ regeneration in response to damage, in particular in the liver and in cutaneous wounds. Both organs consist of a multitude of distinct cell types that contribute to regeneration in an orchestrated manner. It has been proposed that regeneration of the liver is a result of its capability to respond to damage by exerting cellular plasticity. These processes are normally set in place by the concerted action of signaling pathways. Under pathophysiological conditions, however, pathway deregulation leads to compromised regeneration.
We aim to identify the activity of molecular pathways in organs under healthy and disease conditions to identify key cellular signal events that control regeneration. For the study of liver regeneration, we employ primary cell-based assays and in vivo rodent models (damage/regeneration, loss-of-function, and lineage tracing models), and we have access to patient biopsies for molecular profiling applications. State-of-the-art molecular technologies allow genome-wide genetic screens to identify key regulators of regeneration, and their function is interrogated in complex ex vivo cellular systems and animal models. Validation of these regulators will generate novel therapeutic opportunities.
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 Apr 18. doi: 10.1038/ncb3337.
Functional roles of Lgr4 and Lgr5 in embryonic gut, kidney and skin development in mice.
Kinzel B, Pikiolek M, Orsini V, Sprunger J, Isken A, Zietzling S, Desplanches M, Dubost V, Breustedt D, Valdez R, Liu D, Theil D, Müller M, Dietrich B, Bouwmeester T, Ruffner H, Tchorz JS.
Dev Biol. 2014 Jun 15;390(2):181-90.
Protein complex interactor analysis and differential activity of KDM3 subfamily members towards H3K9 methylation.
Brauchle M, Yao Z, Arora R, Thigale S, Clay I, Inverardi B, Fletcher J, Taslimi P, Acker MG, Gerrits B, Voshol J, Bauer A, Schübeler D, Bouwmeester T, Ruffner H.
PLoS One. 2013 Apr 11;8(4):e60549.
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