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Schulte lab - About us

Our research aims to increase the understanding of basic pharmacology and underlying mechanisms of signal transduction and signaling specificity mediated by the Class Frizzled (FZD) receptors.

illustrations of projects in Gunnar Schulte lab
DVL2-myc distribution in mammalian cells. See also Bryja et al 2007, J Cell Sci.

In mammals 10 FZDs (FZD1-10) are known. The FZDs are - among other ligands - activated by 19 mammalian WNTs, a group of secreted lipoglycoproteins with an important role in embryonic development, stem cell regulation and human diseases, such as cancer. So far, it remains obscure, which WNTs activate which FZDs and how ligand binding specifies the downstream signaling events.

Our goal is to map WNT-FZD interaction profiles and to characterize basic pharmacological parameters of distinct WNT/FZD pairs. The ultimate goal, of course, is to find mechanisms that could be employed at therepeutic targets to improve current therapy in human disease as diverse as cancer, neurodegenerative diseases, bone disease, etc.

Using biochemical and anatomical as well as live-cell imaging techniques the dynamics of receptor localisation and association of intracellular signalling molecules are investigated in recombinant cell systems and glial cellular models as well as in vivo.

 

Group members

Current members

Alumni

  • Elisa Arthofer, PhD
  • Fredrik Brand, Master's student from the Lausitz University of Applied Sciences, Germany
  • Jenny Dahlström, Med kand, master's student
  • Jacomijn Dijksterhuis, PhD
  • Carina Halleskog, PhD
  • Rober Helbig, PhD, postdoctoral fellow
  • Belma Hot, PhD
  • Michaela Kilander, PhD
  • Natália Assaife Lopes, PhD student, Faculty of Medicine, University of Lisbon, Portugal
  • Tobias Ludwig, Student from the Free University of Berlin, Germany
  • Javier Becerril Ortega, PhD, postdoctoral fellow
  • Julian Petersen, PhD
  • Tilman Polonio, Student from Heidelberg University, Germany
  • Jana Valnohova, PhD
  • Alice Weithäuser, Master's student from the Free University of Berlin, Germany
illustrations of projects in Gunnar Schulte lab
Subcellular distribution of dishevelled (DVL2-myc; red) in transiently transfected Hek293 cells. DVL2-myc is either distributed evenly throughout the cytoplasm, or aggregates in a punctate pattern of variable size (see also Bryja et al, J Cell Sci 2007).

Projects

 

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Graphical abstract from Halleskog et al 2013 (Cellular Signalling)

Frizzled Pharmacology

The general aim of the project is to generate pharmacological information about the Wnt/Frizzled signaling system as well as to clarify some major questions regarding Frizzled-mediated cellular communication. Issues such as WNT-FZD interaction and selectivity, signaling trafficking, FZD coupling to the phosphoprotein Disheveled as well as heterotrimeric G proteins are the focus of our work. To investigate those questions we use protein biochemistry, determination of second messengers, Calcium imaging, confocal microscopy and live cell imaging.

In addition to the pharmacological assessment of FZD function, we try to understand the role of WNT/FZD signaling in the macrophages of the brain, the microglia. Our recent publication (PhD project of Carina Halleskog) shed light on the proinflammatory effects of WNTs on microglia. These cells have also provided exciting insight into the role of heterotrimeric G proteins in WNT signaling in a physiologically relevant cellular environment with natural receptor stoichiometry.

Research support - past and present

- Vetenskapsrådet
- Hjärnfonden
- Cancerfonden
- Karolinska Institutet
- Knut & Alice Wallenberg Stiftelse
- Signhild Engkvists Stiftelse
- Tore Nilson Stiftelse
- Signe & Olof Wallenius Stiftelse
- Max & Edith Follins Stiftelse
- Fernströms Stiftelsen
- Alex & Eva Wallström Stiftelse
- Jeanssons Stiftelse
- Åke Wiberg Stiftelse
- Åhlén Stiftelse
- Stiftelsen Olle Engkvist Byggmästare
- Socialstyrelsen
- STINT
- KI/NIH Joint PhD
- KID
- GACR (Czech Science Foundation)
- FP7 Marie Skłodowska-Curie actions

Contact

Gunnar Schulte