Gunnar Schulte

Gunnar Schulte

Professor | Docent
Telephone: +46852487933
Visiting address: Solnavägen 9, Biomedicum, 17165 Solna
Postal address: C3 Fysiologi och farmakologi, C3 FyFa Receptorbiologi, 171 77 Stockholm
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About me

  • Gunnar Schulte is Professor in receptor pharmacology and research group leader for the section Receptor Biology and Signaling at the Department of Physiology and Pharmacology. He has a background in biochemistry from the Free University in Berlin/Germany and a PhD in molecular pharmacology (supervisor: Bertil B Fredholm) from Karolinska Institutet. As postdoc he trained first with Ernest Arenas (Karolinska Institutet, Molecular Neurobiology) and later with Roger J Summers (Monash University, Melbourna Australia, GPCR pharmacology) before starting his independent research team "Receptor Biology & Signalling". Gunnar Schulte is also the scientific secretary of the Swedish Society for Medical Research (SSMF) and member on the editorial board/editorial advisory board of Molecular Pharmacology, Pharmacological Reviews, and The Journal of Biological Chemistry.

    Education
    Diploma (biochemistry) - Free University of Berlin, Germany (1992-1998)
    PhD (Molecular Pharmacology) - Karolinska Institutet (1998-2002)
    Postdoc (Molecular Neurobiology) - Karolinska Institutet (2003-2005)
    Postdoc (Molecular Pharmacology - Monash University, Melbourna, Australia (2006)
    Junior Researcher (Receptor Biology & Signaling) - Karolinska Institutet (2007-2014)
    Senior Researcher (Receptor Biology & Signaling) - Karolinska Institutet (2015-2016)
    Professor (Receptor Pharmacology - Karolinska Institutet (2017-)

Research

  • General Research Interest: Frizzled signaling and pharmacology and the role of WNT/Frizzled signaling in biology, physiology and disease. Most importantly my research team tries to understand underlying mechanisms of WNT-receptor interaction, relevance of receptor dynamics and receptor complex composition and specification of downstream signaling. The ultimate aim is to use the new knowlegde to find and create Frizzled-targeting drugs to improve future therapies of human disease.

Articles

All other publications

Grants

  • Swedish Research Council
    1 January 2025 - 31 December 2028
    Diverse signaling systems are attractive targets for anti-cancer therapy, one of which is the WNT/Frizzled signaling system, where secreted WNT proteins activate Frizzled receptors driving cancer cell proliferation, migration and invasion. The WNT/Frizzled signaling systems is of particular interest in pancreatic cancer carrying a mutation in the gene RNF43, which directly amplifies FZD signaling. This opens the opportunity for a precision medicine approach and our recent work on the first small molecules inhibiting Frizzleds validates this hypothesis.My research team has investigated Frizzled transduction mechanisms for more than fifteen years and our recent progress in pharmacology and structural biology (cryogenic electron microscopy, CryoEM), enables us now to understand molecular details of FZD activation, how they contribute to oncogenesis and how they can be targeted pharmacologically. In a combined biochemical, pharmacological and biophysical approach, we will further detail mechanisms of receptor activation, pathway initiation and signal specification to engage in a mechanism-based and structure-guided drug discovery process. The combination of receptor pharmacology, novel genetically encoded biosensors, in silico ligand docking, molecular dynamics simulations and a structure-based approach aiming to obtain high resolution information of Frizzleds in complex with ligands or intracellular binding proteins will provide novel insights into FZDs as a drug target.
  • Swedish Cancer Society
    1 January 2024
    Some tumors are dependent on an overactive signaling pathway where WNT proteins activate Frizzled surface receptors in the tumor cells. The WNT/Frizzled signaling cascade controls survival and cell division in tumor cells and thus contributes to tumor growth. Among other things, rectal, pancreatic, skin and breast tumors show increased activity of WNT/Frizzled signals. Based on our new research findings that it is actually possible to develop small molecule drugs that directly affect Frizzled, we here propose various pharmacological approaches to slow down WNT/Frizzled dependent cell division and metastasis and thus create new treatment options for cancer. With newly developed methodology, we will study how Frizzled surface receptors are activated in tumors. By better understanding the activation mechanisms, we will be able to fight back and reduce FZD activation with specific drugs. We combine basic research into receptor activation with drug development. The new substances that are identified will be tested in various relevant, preclinical cancer models and further developed towards possible clinical use. The idea is to create new drugs through a mechanism-based and structure-driven process that reduces overactive Frizzled signaling in tumors such as FZD5 in pancreatic cancer and FZD7 in colon cancer. With the proposed experiments, we will increase the understanding of the regulation of tumor-causing WNT and Frizzled signals in different tumor forms. A better understanding will also open up new points of attack for therapy. In addition, we now have the opportunity to create drugs that directly affect Frizzled receptors. Such substances have been sought after for decades but the methodology to produce them was lacking. This first step in the development of substances that affect Frizzleds will enable a new therapeutic strategy for cancer therapy. The substances will both be important for cancer treatment as well as for advanced preclinical research around Frizzleds.
  • Deutsche Forschungsgemeinschaft
    1 January 2023 - 31 December 2025
  • Frizzleds – from an impossible drug target to pathway selective inhibition
    Novo Nordisk Foundation
    1 October 2022 - 30 September 2025
  • Deutsche Forschungsgemeinschaft
    1 January 2022 - 31 December 2024
  • Secreted lypoglycoproteins of the WNT family interact with Frizzleds to signal - how does that work and is this system druggable?
    Novo Nordisk Foundation
    1 October 2021 - 30 September 2022
  • Deutsche Forschungsgemeinschaft
    1 January 2021 - 31 December 2023
  • Swedish Cancer Society
    1 January 2021
    Some tumors are dependent on an overactive signaling pathway where WNT proteins activate Frizzled surface receptors in the tumor cells. The WNT/Frizzled signaling cascade controls survival and cell division in tumor cells and thus contributes to tumor growth. Among other things, rectal, pancreatic, skin and breast tumors show increased activity of WNT/Frizzled signals. Based on our new research findings that it is actually possible to develop small molecule drugs that directly affect Frizzled, we here propose different pharmacological approaches to slow down WNT/Frizzled dependent cell division and metastasis and thus create new treatment options for cancer. With newly developed methodology, we will study in detail how Frizzled surface receptors are activated. By better understanding the activation mechanisms, we will be able to fight back and reduce FZD activation with specific drugs. We combine basic research into receptor activation with drug development. The new substances that are identified will be tested in various relevant, preclinical cancer models and further developed towards possible clinical use. The idea is to create new drugs through a mechanism-based and structure-driven process that reduces overactive Frizzled signaling in tumors such as FZD5 in pancreatic cancer. With the proposed experiments, we will increase the understanding of the regulation of tumor-causing WNT and Frizzled signals in different tumor forms. A better understanding will also open up new points of attack for therapy. In addition, we now have the opportunity to create drugs that directly affect Frizzled receptors. Such substances have been sought after for decades but the methodology to produce them was lacking. This first step in the development of substances that affect Frizzleds will enable a new therapeutic strategy for cancer therapy. The substances will both be important for cancer treatment as well as for advanced preclinical research around Frizzleds.
  • Molecular insights into WNT-Frizzled signaling allow drugging Frizzleds in a mechanism-based and structure-guided manner
    Novo Nordisk Foundation
    1 October 2020 - 30 September 2021
  • Swedish Research Council
    1 January 2020 - 31 December 2024
  • Drugging Frizzleds with small molecules - it is actually possible!
    Novo Nordisk Foundation
    1 July 2019 - 30 June 2020
  • Deutsche Forschungsgemeinschaft
    1 January 2019 - 31 December 2021
  • WNT / Frizzled signals - a new target for cancer treatment
    Swedish Cancer Society
    1 January 2018
    Some tumors rely on an overactive signaling pathway where WNT proteins activate Frizzled surface receptors in the tumor cells. The WNT / Frizzled signal cascade controls survival and cell division in tumor cells and thus contributes to tumor growth. Among other things, rectal, pancreatic, skin and breast tumors show increased activity of WNT / Frizzled signals. Based on our new research findings on the ability of Frizzled to give rise to various biochemical changes within the cell, we here propose various pharmacological approaches to slow down WNT / Frizzled dependent cell division and thus create new treatment possibilities for cancer. Previously, we have supported specific signaling pathways that are activated by Frizzled receptors on the inside of cells, with the support of the cancer fund. We will use the new research findings to more accurately describe the interaction between different signal cascades in regulation of tumor growth. We will use models for pancreatic, skin and breast cancer in experiments with cell, zebrafish and mouse models. Patient tests serve to confirm our hypothesis in man. In addition, we will use new measurement methods for Frizzled activation that will enable to find molecules that reduce activation of Frizzled and which are therefore candidates for new cancer treatments. With the proposed experiments, we will increase the understanding of the regulation of tumor-causing WNT signals in various tumor forms. A better understanding will also open new approaches for therapy. In addition, we now have the opportunity to create drugs that directly affect Frizzled receptors. Such substances have been coveted for decades but the methodology was lacking to produce them. This first step in the development of substances that affect Frizzleds will begin a new wave of drug development. The substances will both be important for cancer treatment and for the more advanced preclinical research around Frizzleds.
  • WNT/Frizzled communication as a druggable endocrine signalling system
    Novo Nordisk Foundation
    1 October 2017 - 1 October 2020
  • WNT / Frizzled signals - a new target for cancer treatment
    Swedish Cancer Society
    1 January 2017
    Some tumors rely on an overactive signaling pathway where WNT proteins activate Frizzled surface receptors in the tumor cells. The WNT / Frizzled signal cascade controls survival and cell division in tumor cells and thus contributes to tumor growth. Among other things, rectal, pancreatic, skin and breast tumors show increased activity of WNT / Frizzled signals. Based on our new research findings on the ability of Frizzled to give rise to various biochemical changes within the cell, we here propose various pharmacological approaches to slow down WNT / Frizzled dependent cell division and thus create new treatment possibilities for cancer. Previously, we have supported specific signaling pathways that are activated by Frizzled receptors on the inside of cells, with the support of the cancer fund. We will use the new research findings to more accurately describe the interaction between different signal cascades in regulation of tumor growth. We will use models for pancreatic, skin and breast cancer in experiments with cell, zebrafish and mouse models. Patient tests serve to confirm our hypothesis in man. In addition, we will use new measurement methods for Frizzled activation that will enable to find molecules that reduce activation of Frizzled and which are therefore candidates for new cancer treatments. With the proposed experiments, we will increase the understanding of the regulation of tumor-causing WNT signals in various tumor forms. A better understanding will also open new approaches for therapy. In addition, we now have the opportunity to create drugs that directly affect Frizzled receptors. Such substances have been coveted for decades but the methodology was lacking to produce them. This first step in the development of substances that affect Frizzleds will begin a new wave of drug development. The substances will both be important for cancer treatment and for the more advanced preclinical research around Frizzleds.
  • Cell-cell communication in brain tumors is important for tumor induction, maintenance and spreading
    Swedish Cancer Society
    1 January 2016
    Brain tumors such as glioma belong to the most angry cancers with very short survival after diagnosis. In this project, we focus on the communication between tumor cells in the brain and the brain's immune cells using a signaling system called WNT / Frizzled. The signaling system is important in several types of cancer and is found to be of importance also for glioma. Unfortunately, the signal transmission through WNT / Frizzled is so complex that we do not understand how communication works at the molecular level. Because of this, there are currently no drugs that are able to selectively attack WNT / Frizzled communication. During the project, we want to increase our understanding of the WNT / Frizzled signaling in particular between glioma cells and the brain's immune cells. We want to characterize the significance of the WNT / Frizzled signals to the emergence, maintenance and spread of the glioma cells in the brain. The interaction between astrocytes and glioma cells is in focus as we believe it benefits the tumor spread. In addition, the WNT signals appear to be important for a localized reduction of the immune system in the tumor, which in turn favors tumor survival. Thus, we have identified two important goals for a mechanism-based glioma treatment. To be able to, with pharmacological agents, interfere with cellular interaction between the glioma cells and the brain's immune cells for improved treatment, we will use the newly acquired knowledge of WNT / Frizzled signals to find and create drugs that block tumor-supporting WNT / Frizzled signals in glioma. It is hoped that our research will help to develop drugs that work directly at Frizzleds. These tumor-inhibiting substances could be used as a supplement to more conventional therapy to improve patients' situation. Such substances are also attractive for the treatment of other cancers and diseases.
  • Swedish Research Council
    1 January 2016 - 31 December 2019
  • Deutsche Forschungsgemeinschaft
    1 January 2016 - 31 December 2020
  • Cell-cell communication in brain tumors is important for tumor induction, maintenance and spreading
    Swedish Cancer Society
    1 January 2015
    Brain tumors such as glioma belong to the most angry cancers with very short survival after diagnosis. In this project, we focus on the communication between tumor cells in the brain and the brain's immune cells using a signaling system called WNT / Frizzled. The signaling system is important in several types of cancer and is found to be of importance also for glioma. Unfortunately, the signal transmission through WNT / Frizzled is so complex that we do not understand how communication works at the molecular level. Because of this, there are currently no drugs that are able to selectively attack WNT / Frizzled communication. During the project, we want to increase our understanding of the WNT / Frizzled signaling in particular between glioma cells and the brain's immune cells. We want to characterize the significance of the WNT / Frizzled signals to the emergence, maintenance and spread of the glioma cells in the brain. The interaction between astrocytes and glioma cells is in focus as we believe it benefits the tumor spread. In addition, the WNT signals appear to be important for a localized reduction of the immune system in the tumor, which in turn favors tumor survival. Thus, we have identified two important goals for a mechanism-based glioma treatment. To be able to, with pharmacological agents, interfere with cellular interaction between the glioma cells and the brain's immune cells for improved treatment, we will use the newly acquired knowledge of WNT / Frizzled signals to find and create drugs that block tumor-supporting WNT / Frizzled signals in glioma. It is hoped that our research will help to develop drugs that work directly at Frizzleds. These tumor-inhibiting substances could be used as a supplement to more conventional therapy to improve patients' situation. Such substances are also attractive for the treatment of other cancers and diseases.
  • Cell-cell communication in brain tumors is important for tumor induction, maintenance and spreading
    Swedish Cancer Society
    1 January 2014
    Brain tumors such as glioma belong to the most angry cancers with very short survival after diagnosis. In this project, we focus on the communication between tumor cells in the brain and the brain's immune cells using a signaling system called WNT / Frizzled. The signaling system is important in several types of cancer and is found to be of importance also for glioma. Unfortunately, the signal transmission through WNT / Frizzled is so complex that we do not understand how communication works at the molecular level. Because of this, there are currently no drugs that are able to selectively attack WNT / Frizzled communication. During the project, we want to increase our understanding of the WNT / Frizzled signaling in particular between glioma cells and the brain's immune cells. We want to characterize the significance of the WNT / Frizzled signals to the emergence, maintenance and spread of the glioma cells in the brain. The interaction between astrocytes and glioma cells is in focus as we believe it benefits the tumor spread. In addition, the WNT signals appear to be important for a localized reduction of the immune system in the tumor, which in turn favors tumor survival. Thus, we have identified two important goals for a mechanism-based glioma treatment. To be able to, with pharmacological agents, interfere with cellular interaction between the glioma cells and the brain's immune cells for improved treatment, we will use the newly acquired knowledge of WNT / Frizzled signals to find and create drugs that block tumor-supporting WNT / Frizzled signals in glioma. It is hoped that our research will help to develop drugs that work directly at Frizzleds. These tumor-inhibiting substances could be used as a supplement to more conventional therapy to improve patients' situation. Such substances are also attractive for the treatment of other cancers and diseases.
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Employments

  • Professor, Receptor Pharmacology, Department of Physiology and Pharmacology, Karolinska Institutet, 2017-

Degrees and Education

  • Docent, Karolinska Institutet, 2008
  • Doctor Of Philosophy, Department of Physiology and Pharmacology, Karolinska Institutet, 2002

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