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Signaling complexes in membranes
The Piehler group aims to uncover the mechanistic principles governing class I/II cytokine receptor signaling. These receptors have key functions in hematopoiesis, immunity and inflammation and their dysregulation has been implicated in various diseases such as leukemias. The group develops quantitative techniques for resolving the spatiotemporal organization and activation of class I/II cytokine receptor signaling complexes in cellular membranes down to single molecule level.
Research topics
- Spatiotemporal dynamics of cytokine receptor assembly
- Activation mechanism of Janus family tyrosine kinases (JAKs)
- Regulation of cytokine signaling by the subcellular membrane environment
- Dysregulation of signal activation by oncogenic mutations
- Manipulation of cellular signaling via functionalized nanomaterials
Model systems
- Endogenous and transfected receptors in mammalian cells
- Reconstituted membrane systems
- Isolated proteins and protein complexes
Methods
- Single molecule fluorescence imaging & single molecule FRET
- Protein expression and purification
- Solid-supported membrane model systems
- Surface functionalization & patterning
- Nanoparticle biofunctionalization
Selected publications
Wilmes S, Hafer M, Vuorio J, Tucker JA, Winkelmann H, Löchte S, Stanly TA, Pulgar Prieto KD, Poojari C, Sharma V, Richter CP, Kurre R, Hubbard SR, Garcia KC, Moraga I, Vattulainen I, Hitchcock IS, & Piehler J (2020) Mechanism of homodimeric cytokine receptor activation and dysregulation by oncogenic mutations. Science 367(6478):643-652, doi: 10.1126/science.aaw3242. pdf
Richter D, Moraga I, Winkelmann H, Birkholz O, Wilmes S, Schulte M, Kraich M, Kenneweg H, Beutel O, Selenschik P, Paterok D, Gavutis M, Schmidt T, Garcia KC, Muller TD, & Piehler J (2017) Ligand-induced type II interleukin-4 receptor dimers are sustained by rapid re-association within plasma membrane microcompartments. Nat Commun 8:15976, doi: 10.1038/ncomms15976. pdf
Wilmes S, Beutel O, Li Z, Francois-Newton V, Richter CP, Janning D, Kroll C, Hanhart P, Hotte K, You C, Uze G, Pellegrini S, & Piehler J (2015) Receptor dimerization dynamics as a regulatory valve for plasticity of type I interferon signaling. J Cell Biol 209(4):579-593, doi: 10.1083/jcb.201412049. pdf
