© Raphael Schleutker

Research Topic

Our research goal is to understand how cells interpret multifactorial instructions within the context of a tissue and organ. Intriguingly these cues, including physical, biochemical, and nutritional factors, must be integrated according to the current status of the cell, such as cell cycle or differentiation state. Ultimately how cells read multiple signals within their current context to change identity or state remains incompletely understood. To address this objective, we use hair follicle stem cell niche development and homeostasis in which multiple cell types interface as a paradigm to dissect how signal integration mediates cell fate acquisition as well as tissue morphogenesis and homeostasis. In particular we aim to understand the cellular, molecular, and physical basis of signal integration. To analyse and perturb signaling factors and pathways, we utilize in vivo models as well as in vitro 2D, 3D organoid, and bioengineered modalities together with next generation sequencing, quantitative confocal live imaging, 2-photon intravital imaging, and classical developmental biology and histological techniques. Given the universality of signal integration in the regulation of stem cell niche development, these long-standing questions have application to other organ systems.

Selected Publications

  • Kim CS, Ding X, Allmeroth K, Biggs LC, Kolenc OI, L'Hoest N, Chacón-Martínez CA, Edlich-Muth C, Giavalisco P, Quinn KP, Denzel MS, Eming SA, Wickström SA. (2020). Glutamine Metabolism Controls Stem Cell Fate Reversibility and Long-Term Maintenance in the Hair Follicle. Cell Metabolism, 32(4):629-642.e8. doi: 10.1016/j.cmet.2020.08.011.
  • Nava MM, Miroshnikova YA, Biggs LC, Whitefield DB, Metge F, Boucas J, Vihinen H, Jokitalo E, Li X, García Arcos JM, Hoffmann B, Merkel R, Niessen CM, Dahl KN, Wickström SA. (2020). Heterochromatin-Driven Nuclear Softening Protects the Genome against Mechanical Stress-Induced Damage. Cell,181(4):800-817.e22. doi: 10.1016/j.cell.2020.03.052.
  • Binder M, Biggs LC, Kronenberg MS, Schneider P, Thesleff I, Balic A. (2020). Novel strategies for expansion of tooth epithelial stem cells and ameloblast generation. Scientific Reports, 10(1):4963. doi: 10.1038/s41598-020-60708-w.
  • Binder M, Chmielarz P, Mckinnon PJ, Biggs LC, Thesleff I, Balic A. (2019). Functionally Distinctive Ptch Receptors Establish Multimodal Hedgehog Signaling in the Tooth Epithelial Stem Cell Niche. Stem Cells, 37(9):1238-1248. doi: 10.1002/stem.3042.