Receptor biology and signaling – Schulte Lab

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.


About us

Two illustrations of membran
Illustration from Kowalski-Jahn & Schihada et al. 2021 Photo: N/A
An illustration from the text Kozielewicz et al. 2021; Wesslowski & Kozielewicz et al. 2020).
A NanoBiT/BRET assay design allowed Pawel Kozielewicz to assess WNT binding to a full length FZD for the first time. This breakthrough allowed pharmacological characterization of WNT-FZD binding (Kozielewicz et al. 2021; Wesslowski & Kozielewicz et al. 2020). Photo: N/A

The class F of G protein-coupled receptors (GPCRs) consists of ten Frizzleds (FZD1-10) and Smoothened (SMO). 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. In the Schulte lab, we investigate how ligands activate FZDs in order to initiate intracellular changes. In this effort, we focus on ligand-receptor interaction, ligand-induced conformational changes in the receptor and aspects of conformational selection determining which downstream signaling pathways are activated. Thereby we hope to provide better insight into WNT-FZD binding mechanisms and selectivity and how intracellular signaling is initiated and specified by the individual FZD paralogues.


An illustration from the text Schihada et al. 2021
Fluorescent sensors based on cpGFP enabled Hannes Schihada in the Schulte lab to visualize WNT-induced conformational changes in several FZD paralogues (Schihada et al. 2021). Photo: N/A

During the recent years, we have developed expertise in the use and design of genetically encoded biosensors that monitor ligand binding to FZDs, FZD conformational dynamics, FZD-effector binding and downstream effector activation. Furthermore, we combine these live cell assessments of the most upstream events of WNT-induced effects with in silico approaches such as molecular dynamics simulations and computational modelling to provide mechanistic insight into receptor activation and receptor complex dynamics on a molecular level.

One of the most important concepts that we have developed and that presents an important contribution to the field is the idea that FZDs are - similar to other GPCR – molecular machines that are defined by a structural flexibility and dynamics. Appreciation of this intrinsic flexibility is the basis for understanding receptor activation, receptor-mediated signal initiation and for targeting FZDs for therapy. Several important contributions from the Schulte lab have contributed to understand this central phenomenon (Wright and Kozielewicz et al. 2019; Kozielewicz et al. 2020; Turku et al. 2021; Kowalski-Jahn and Schihada et al. 2021; Schihada et al. 2021).

Our goal is to understand the complexity of WNT-induced events that determine the kinetics and nature of WNT signaling pathways governing embryonic development and tissue homeostasis. Since deregulated WNT signaling results in devastating diseases exemplified by many different and common forms of tumors (e g breast, intestinal, pancreatic cancer), bone disease, fibrosis and neurological disorders, we are convinced that targeting FZDs pharmacologically will open exciting strategies for the therapy of severe diseases.

Understanding how FZDs mediate WNT signaling to drive proliferation in a tumor or in a fibrotic tissue will allow us to design drugs that interfere with this message for therapeutic use. Our lab has shown for the first time that FZDs can be pharmacologically targeted by small molecule drugs (Kozielewicz et al. 2020) and we are currently developing this strategy to find drug-like compounds for anti-cancer treatment.


The computer simulation shows the interaction between FZD6 (white) and the small drug-like molecule SAG13 (purple).

The recent advances in our understanding of the details of FZD activation have been possible because of the development of biophysical assays that are suitable to dissect mechanistic aspects of signaling in an unprecedented manner. Furthermore, these assays are building the technological basis for drug screening efforts, which will explore the chemical matter on the quest for new drugs to treat cancer and other devastating human disorders.

Wright SC, Kozielewicz P, Kowalski-Jahn M, Petersen J, Bowin CF, Slodkowicz G, Marti-Solano M, Rodríguez D, Hot B, Okashah N, Strakova K, Valnohova J, Babu MM, Lambert NA, Carlsson J, Schulte G. A conserved molecular switch in Class F receptors regulates receptor activation and pathway selection. Nat Commun. 2019 Feb 8;10(1):667. doi: 10.1038/s41467-019-08630-2. PMID: 30737406

Kozielewicz P, Turku A, Bowin CF, Petersen J, Valnohova J, Cañizal MCA, Ono Y, Inoue A, Hoffmann C, Schulte G. Structural insight into small molecule action on Frizzleds. Nat Commun. 2020 Jan 21;11(1):414. doi: 10.1038/s41467-019-14149-3. PMID: 31964872

Wesslowski J, Kozielewicz P, Wang X, Cui H, Schihada H, Kranz D, Karuna M P, Levkin P, Gross JC, Boutros M, Schulte G, Davidson G. eGFP-tagged Wnt-3a enables functional analysis of Wnt trafficking and signaling and kinetic assessment of Wnt binding to full-length Frizzled. J Biol Chem. 2020 Jun 26;295(26):8759-8774. doi: 10.1074/jbc.RA120.012892. Epub 2020 May 7. PMID: 32381507

Schihada H, Kowalski-Jahn M, Turku A, Schulte G. Deconvolution of WNT-induced Frizzled conformational dynamics with fluorescent biosensors. Biosens Bioelectron. 2021 Apr 1;177:112948. doi: 10.1016/j.bios.2020.112948. Epub 2020 Dec 30. PMID: 33486136

Kozielewicz P, Shekhani R, Moser S, Bowin CF, Wesslowski J, Davidson G, Schulte G. Quantitative Profiling of WNT-3A Binding to All Human Frizzled Paralogues in HEK293 Cells by NanoBiT/BRET Assessments. ACS Pharmacol Transl Sci. 2021 May 11;4(3):1235-1245. doi: 10.1021/acsptsci.1c00084. eCollection 2021 Jun 11. PMID: 34151213

Turku A, Schihada H, Kozielewicz P, Bowin CF, Schulte G. Residue 6.43 defines receptor function in class F GPCRs. Nat Commun. 2021 Jun 24;12(1):3919. doi: 10.1038/s41467-021-24004-z. PMID: 34168128

Xu L, Chen B, Schihada H, Wright SC, Turku A, Wu Y, Han GW, Kowalski-Jahn M, Kozielewicz P, Bowin CF, Zhang X, Li C, Bouvier M, Schulte G, Xu F. Cryo-EM structure of constitutively active human Frizzled 7 in complex with heterotrimeric Gs. Cell Res. 2021 Jul 8. doi: 10.1038/s41422-021-00525-6. Online ahead of print. PMID: 34239071

Kowalski-Jahn M, Schihada H, Turku A, Huber T, Sakmar TP, Schulte G. Frizzled BRET sensors based on bioorthogonal labeling of unnatural amino acids reveal WNT-induced dynamics of the cysteine-rich domain. Sci Adv. 2021 Nov 12;7(46):eabj7917. doi: 10.1126/sciadv.abj7917. Epub 2021 Nov 10. PMID: 34757789



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


Selected publications

Review articles

Molecular Pharmacology of Class F Receptor Activation.
Kozielewicz P, Turku A, Schulte G
Mol Pharmacol 2020 02;97(2):62-71

Structural insight into Class F receptors - What have we learnt regarding agonist-induced activation?
Schulte G, Kozielewicz P
Basic Clin. Pharmacol. Toxicol. 2019 Mar

Frizzleds as GPCRs - More Conventional Than We Thought!
Schulte G, Wright SC
Trends Pharmacol. Sci. 2018 09;39(9):828-842

Frizzleds and WNT/β-catenin signaling--The black box of ligand-receptor selectivity, complex stoichiometry and activation kinetics.
Schulte G
Eur. J. Pharmacol. 2015 Sep;763(Pt B):191-5

WNT/Frizzled signalling: receptor-ligand selectivity with focus on FZD-G protein signalling and its physiological relevance: IUPHAR Review 3.
Dijksterhuis JP, Petersen J, Schulte G
Br. J. Pharmacol. 2014 Mar;171(5):1195-209

International Union of Basic and Clinical Pharmacology. LXXX. The class Frizzled receptors.
Schulte G
Pharmacol. Rev. 2010 Dec;62(4):632-67

beta-Arrestins - scaffolds and signalling elements essential for WNT/Frizzled signalling pathways?
Schulte G, Schambony A, Bryja V
Br. J. Pharmacol. 2010 Mar;159(5):1051-8

The Frizzled family of unconventional G-protein-coupled receptors.
Schulte G, Bryja V
Trends Pharmacol. Sci. 2007 Oct;28(10):518-25


The Dr. GPCR podcast #46: Gunnar Schulte interviewed by Dr Yamina Berchiche.

Listen here

Full publication list

Full list of publications - PubMed

Staff and contact

Group leader

All members of the group


  • Maria Kowalski-Jahn, postdoc
  • Ainoleena Turku, postdoc
  • Shane Wright, postdoc
  • 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
  • Carl Fredrik Bowin (PhD student)
  • Hannes Schihada, postdoc

Team - Molecular pharmacology of GPCRs

illustration of molecules and a magnefying glass
Molecular Pharmacology of G protein-coupled receptors Photo: N/A

We are interested in understanding the role of GPCRs in health and disease, with a focus on cancer and obesity. Of particular interest to us are understudied orphan GPCRs. These receptors bear untapped therapeutic potential and a lof of them are highly expressed or mutated in these diseases. To shed light on the functions of orphan GPCRs in these conditions, we aim to employ an integrative approach. We will study these proteins in different systems, ranging from HEK293 cells to patients' samples, and investigate phenomena at different levels: from receptor conformational changes to impact on cell phenotype.

Our methodologies include but are not limited to:

  • Bioluminescence resonance energy transfer (BRET)
  • CRISPR-Cas9 genome editing
  • Molecular modelling with ligand docking and molecular dynamics simulations
  • Proximal labelling techniques
  • Analysis of large genomic datasets


  • Analysis of the role of orphan GPCRs in cancer
  • Investigations into orphan GPCRs as regulators of metabolism
  • Understandng the pharmacology of Smoothened

Team leader

Profile image

Paweł Kozielewicz

Assistant Professor


Choi Tsang

Research Assistant

Alexander De Rosa

Affiliated to Research

Conference contribution


Gunnar Schulte is an invited speaker at the 11th MPGPCR (Molecular Pharmacology of GPCRs) meeting in Melbourne held the 15th-17th of Nov 2023.

Gunnar Schulte contributes to the Nordic Symposium at the 19th World Congress of Basic & Clinical Pharmacology 2023 (WCP2023) with a talk on the 5th of July 2023.

The Schulte lab will be well-represented at the Gordon Research Conference (GRC) and Gordon Research Seminar (GRS)in Molecular Pharmacology in June 11-16 2023. Gunnar Schulte and Lukas Graetz are invited speakers.


4GPCRnet – International Symposium Sept 26-29, 2022 (Leipzig, Germany) – Gunnar Schulte is invited speaker

25th Jubilee Meeting on Signal Transduction Nov 2 - 4, 2022 (Weimar, Germany) – Gunnar Schulte is invited speaker (Hot Topics in Signal Transduction)


G protein-coupled receptors - from physiology to drugs

8th International meeting.
9-11 October 2019, Montpellier, France.

EB2019 New Opportunities in Targeting WNT Signaling

The ASPET Annual Meeting is where pharmacology meets experimental biology in ONE community.
8 April 2019, Orlando, Florida, USA.

Pharmacology 2019

Organised by The Swedish Society for Pharmacology, Clinical Pharmacology and Therapeutics, the Swedish Society of Medicine.
2-3 April 2019 at Karolinska Institutet, Sweden.

GRC Molecular Pharmacology (Gordon Ressearch Conference - "How Form, Function, Content and Context Shape GPCR Signaling"

The 2019 Gordon Research Conference on Molecular Pharmacology will highlight the latest advances in understanding G protein-coupled receptors (GPCRs) and how they mediate regulation of physiological processes. GPCRs are well established effective therapeutic targets and presentations will focus on how we can further improve therapeutic development across diverse disease states, including cancer, metabolic disorders, cardiovascular disease, and pain.

10-15 February 2019, Ventura Beach Marriott, Ventura, CA, US


GPCR Pharmacology: The Next Generation

The Royal Danish Academy of Sciences and Letters
31 October - 2 November 2018,
Copenhagen, Denmark


GPCR workshop 2017

Workshop organised by ConfometRX Research Foundation and Monash Institute of Pharmaceutical Sciences, Melbourne, Australia. Key themes for the 2017 Workshop were advances in structural understanding of GPCRs, novel signaling paradigms, the intersection of computational advances and chemical biology, biologics, and preclinical and clinical translation.
5-9 December 2017, Sheraton Kona, Hawaï


6th BPS Focused Meeting on Cell Signalling

Organised by the British Pharmacological Society.
18-19 April 2016, University of Leicester, Stamford Court, United Kingdom


GRS Molecular Pharmacology (Gordon Research Seminar, GRS) - "New Fronties in GPCR Signaling: From Biased Agonism to Disease Progression"

The Gordon Research Seminar on Molecular Pharmacology is a unique forum for graduate students, post-docs, and other scientists with comparable levels of experience and education to present and exchange new data and cutting edge ideas.
31 January - 1 February, 2015, Ventura Beach Marriott, USA

Master's and PhD projects

Carl Frerik-Bowin thesis cover 2021
Carl Frerik-Bowin thesis cover 2021 Photo: N/A


Doctoral thesis Carl- Fredrik Bowin (2021-11-12)

“WNT/Frizzled signaling – Illuminating the road towards pathway selectivity”

doctoral thesis covers
Shane C. Wright


Doctoral thesis Shane C. Wright (2019-01-25)

"Activation mechanisms of Class F receptors"


doctoral thesis covers
Jana Valnohova


Doctoral thesis Jana Valnohova (2018-11-09)

"Novel insights into dishevelled and frizzled function"

doctoral thesis covers
Belma Hot


Doctoral thesis Belma Hot (2017-04-28)

"Molecular aspects of WNT/Frizzled signalling in brain angiogenesis"

doctoral thesis covers
Elisa Arthofer
doctoral thesis covers
Katerina Straková
doctoral thesis covers
Julian Petersen


Doctoral thesis Julian Petersen (2016-01-29)

"Structural and functional analysis of WNT receptors : with emphasis on FZD6"

doctoral thesis covers
Jacomijn Dijksterhuis


Doctoral thesis Jacomijn Dijksterhuis (2015-03-06)

"WNT/FZD signaling : an odyssey from molecular pharmacology to brain (patho)physiology"

doctoral thesis covers
Michaela Kilander
doctoral thesis covers
Carina Halleskog

Doctoral thesis Carina Halleskog (2013-06-14)

"WNT signaling in microglia : WNTs as novel regulators of microglia"

doctoral thesis covers
Frand Brand
doctoral thesis covers
Gunnar Schulte

Vacant positions

I would be happy to assist with applications for external support in form of postdoctoral or PhD student fellowships.

I strongly encourage fellows eligible for postdoctoral application to Hjärnfonden and SSMF to contact me with a letter of interest, CV and letters of recommendation.