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Multicellular Signaling Dynamics
We study how the dynamics of cell signaling regulates the variety of complex cell fate decisions in the formation of multicellular organisms. Our focus is the Notch signaling pathway which is essential in the development and tissue homeostasis and whose dysfunction leads to various pathologies including many human cancers. We apply multidisciplinary techniques and follow, quantify, and spatiotemporally link physiological signaling events alongside the activation cascade from the membrane to the nucleus in single cells as well as different organoid model systems.
Research topics
- Spatiotemporal dynamics of Notch signaling activation
- Determination of molecule numbers involved in signaling transduction
- Identification of context dependent differences of signaling activation
- Characterization of signaling dysregulation in pathogenesis
Model systems
- Endogenous and overexpression systems in mammalian cells
- hiPS cell derived organoid models and organ-on-chip
- Cell-cell co-cultures
- Reconstituted membrane system
Methods
- Gene engineering (knock-in and knock-out using CRISRP/Cas9)
- Organoid differentiation
- Microfluidics controlled cell-cell pairing
- Live cell microscopy
- Proteomics
Selected Publications
Cao R, Gozlan O, Airich A, Tveriakhina L, Zhou H, Jiang H, Cole PA, Aster JC, Klein T, Sprinzak D, Blacklow SC. Structural requirements for activity of Mind bomb1 in Notch signaling. Structure. 2024 Oct 3;32(10):1667-1676.e5. pdf
Tveriakhina L, Scanavachi G, Egan ED, Da Cunha Correia RB, Martin AP, Rogers JM, Yodh JS, Aster JC, Kirchhausen T, Blacklow SC. Temporal dynamics and stoichiometry in human Notch signaling from Notch synaptic complex formation to nuclear entry of the Notch intracellular domain. Dev Cell. 2024 Jun 3;59(11):1425-1438.e8. pdf
Martin AP, Bradshaw GA, Eisert RJ, Egan ED, Tveriakhina L, Rogers JM, Dates AN, Scanavachi G, Aster JC, Kirchhausen T, Kalocsay M, Blacklow SC. A spatiotemporal Notch interaction map from plasma membrane to nucleus. Sci Signal. 2023 Aug;16(796):eadg6474. pdf
Tveriakhina L, Schuster-Gossler K, Jarrett SM, Andrawes MB, Rohrbach M, Blacklow SC, Gossler A. The ectodomains determine ligand function in vivo and selectivity of DLL1 and DLL4 toward NOTCH1 and NOTCH2 in vitro. Elife. 2018 Oct 5;7:e40045. pdf
Preuße K, Tveriakhina L, Schuster-Gossler K, Gaspar C, Rosa AI, Henrique D, Gossler A, Stauber M. Context-Dependent Functional Divergence of the Notch Ligands DLL1 and DLL4 In Vivo. PLoS Genet. 2015 Jun 26;11(6):e1005328. pdf
