Epithelial Regeneration & Cancer

Marc Leushacke transferred to the Skin Research Institute of Singapore on the 1 October 2020. 

Using conditional mouse models and organotypic 3D culture methods, we are investigating the regulation of stem cells during development, adult homeostasis, regeneration and cancer with the aim of identifying novel regulatory factors controlling their behavior.

1. The epithelial lining from multiple organs continuously renews, as cells turn over while carrying out their dedicated functions. Adult stem cells residing in specific compartments are responsible for homeostasis in these tissues as well as tissue regeneration in response to injury. Stem cell intrinsic factors as well as extrinsic cues provided by the immediate microenvironment, known as the niche, regulate organ-specific stem cell behaviors that ensure tissue homeostasis. Our goal is to better understand the behavior of stem cells in healthy tissues in order to harness their potential for clinical applications in regenerative medicine. Recently, significant progress has been made regarding the isolation and in vitro propagation of adult tissue from multiple organs as 3D cultures resembling part of the cellular architecture, hierarchy and physiology of the in vivo counterpart. We employ these organotypic 3D culture methods to explore the regenerative medicine potential of human adult stem cells. We further employ this in vitro technology as well as in vivo cancer mouse models to characterize and model genetic and epigenetic mechanisms involved in epithelial tumor formation and progression with the aim to develop novel, more effective therapies.

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2. Wnt signaling mediates key developmental and homeostatic processes in mammals. Deregulation of the Wnt pathway contributes to developmental defects as well as to the initiation and progression of human diseases including cancer. Consequently, Wnt signaling is subjected to stringent positive and negative feedback loops that promote proper development and homeostasis yet avoid aberrant growth. During adulthood the four secreted R-SPONDIN ligands have been recently identified to act via their cognate Leucine-rich repeat-containing G-protein coupled receptors (LGRs) 4/5/6 to amplify WNT signaling in mammals. We aim to investigate the relationship between the individual LGRs and their related R-SPONDIN ligands in different tissues including the Skin, Liver and GI tract during embryogenesis and adulthood.

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