Peter ten Dijke Group

Chemical Signaling

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Our Focus

Our research efforts are focussed on:  

(1) Elucidating the molecular and cellular mechanisms that control tumour cell behaviour. We continue to uncover pivotal determinants by which the cytokine TGF-b switches non-invasive cancer cells into aggressive therapy-resistant cancer cells  

(2) Targeting tumour-promoting signalling pathways to develop more effective cancer therapies. For example, we are developing bifunctional antibodies to inhibit TGF-b-induced pro-tumorigenic responses in a cell type-specific manner. In addition, we are developing bifunctional small molecules that recruit cancer-inducing proteins to the proteasome for degradation.  

(3) Investigating the role of tumour-derived extracellular vesicles (EVs) in inter-cellular communication and their use as cancer biomarkers. We have been able to detect and isolate tumour-derived EVs using an agent that specifically binds an oncofoetal-specific protein modification.  

  

Two main questions that are being addressed:  

(1) How can we selectively block TGF-β-induced tumour-promoting responses while preserving its essential role in maintaining tissue homeostasis  

(2) Can tumour-derived EVs be used for early cancer detection and monitoring, and how do they promote cancer progression?   

About Peter ten Dijke

My Research

Peter ten Dijke received his Ph.D. degree in 1991 from Wageningen University, The Netherlands based on his research on the identification of the third isoform of TGFβ performed at Oncogene Science, Inc., New York, USA. He did his postgraduate studies with Kohei Miyazono and Carl-Henrik Heldin at the Ludwig Institute for Cancer Research (LICR), Uppsala, Sweden. In 1994, he became group leader at LICR and moved in 1999 to the Netherlands Cancer Institute, Amsterdam, The Netherlands. In 2005, he became a professor of molecular cell biology at Leiden University Medical Center.

The overall aim of our work is to obtain a fundamental understanding on how cells communicate with each other, how this contributes to cancer progression when it goes awry ,and how we can manipulate it for therapeutic benefit. We use innovative integrated biological, genetic and chemical approaches to monitor and manipulate dynamic signal transduction processes. In particular, our research is focussed on elucidating the molecular mechanisms by which the multifunctional TGF-b family cytokines maintain tissue homeostasis and promote cancer progression.

Breakthrough discoveries were the identification and functional characterization of TGF-b family cell surface receptors and their downstream SMAD effector proteins. Moreover, we identified pivotal (druggable) regulators of TGF-b-induced epithelial of cancer cell plasticity and metastasis. Our research on how TGF-β controls tumor angiogenesis have led to new targeting agents that are being tested clinically. More recently, new insights were obtained into how ubiquitin modifications of TGF-β receptors and SMADs control their function and stability. The E3 ubiquitin ligases and deubiquitinating enzymes that were identified are novel targets for (immune) oncology drugs.

Awards
  • 2022: Marshall RUrist lecture Award

  • 2021: Member of Academy of Europe

  • 2018: Member of Royal Netherlands Academy of Arts and Sciences

  • 2016: EMBO member

  • 2015: Noreen Cunningham lecture award

  • 2015: FEBS national lecture award

  • 2015: Chang Jiang Scholar award from the Chinese Ministry of Education

  • 2010: LUMC Education prize for best Frontiers in Science course for master students biomedical sciences

  • 2006: VICI grant Netherlands Organization for Scientific Research

  • 2005: Honorary Doctor of Medicine Uppsala University, Sweden

  • 1998: Small Fernström prize for promising scientist in Sweden

  • 1992-1993: Long-term EMBO Fellowship

Key Publications
  1. Zhang J, van der Zon G, Ma J, Mei H, Cabukusta B, ... & Ten Dijke P. ST3GAL5 catalysed gangliosides inhibit TGF-β-induced epithelial-mesenchymal transition via TβRI degradation. EMBO J., in press.

  2. Xie F, Zhou X, Li H, Su P, Liu S, ... & Ten Dijke P*, Zhou F*, Zhang L*. USP8 promotes cancer progression and extracellular vesicle-mediated CD8+ T cell exhaustion by deubiquitinating the TGF-β receptor TβRII. EMBO J. 2022 41:e108791. (*corresponding author)

  3. Liu S, González-Prieto R, Zhang M, Geurink PP, Kooij R, ... & Ten Dijke P. Deubiquitinase activity profiling identifies UCHL1 as a candidate oncoprotein that promotes TGFβ-Induced breast cancer metastasis. Clin Cancer Res. 2020 26:1460-1473.

  4. Zhang L, Zhou F, de Vinuesa A G, de Kruijf E M, Mesker W E, ... & Ten Dijke P (2013). TRAF4 promotes TGF-β receptor signaling and drives breast cancer metastasis. Molecular Cell, 51, 559-572.

  5. Nakao A, Afrakhte M, Morn A, Nakayama T, Christian J L, ... & Ten Dijke P. (1997). Identification of Smad7, a TGFβ-inducible antagonist of TGF-β signalling. Nature, 389, 631-635.

Members

Peter ten Dijke
Group leader
Agustin Enciso Martinez    
PostDoc
Chao Li    
PhD student
Chuannan Fan    
PhD student
David Baker    
Associate professor
Dima Almandawi    
Technician
Emma Boerrigter    
PhD student
Gerardus van der Zon    
Technician
Jiying Zhang    
Phd student
Jun Yang Ong    
Postdoc
Kun Fan    
Phd student
Maarten van Dinther    
Technician
Marius Wits    
PostDoc
Midory Thorikay    
Analyst
Qian Wang    
Post Doc
Shaima Abdalla    
Phd student
Weixin Liao    
Phd student