Spatio-Temporal Regulation of Cell Signaling – Scaffolds & Phosphoinositides

At a glance

Our aim is to identify novel mechanisms of cellular signaling important in cancer and to propose innovative diagnostic and therapeutic approaches.

We are investigating novel pathways controlling cell signaling and cell-cell communication and exploring their potential benefit for the cancer field. We concentrate our studies on scaffold proteins (heparan sulfate proteoglycans and PDZ proteins) and signaling lipids (phosphoinositides) that are important molecules for the spatio-temporal organisation of cell signaling.

In particular we study their effect on the half-life of signaling receptors, their role in cell-cell communication and their impact on nuclear processes. We thereby hope to pave the way for innovative therapeutic approaches.



Main research fields and interests

Cell signalling, scaffold proteins, signalling lipids, membrane compartmentalization, nuclear processes, cell biology, biochemistry, model organisms, cancer, drug discovery.


Specific research projects

Living cells display complex signal processing behaviors mediated by networks of proteins specialized for signal transduction. The wiring of the signaling pathways, or the input-ouput relationship, is coordinated by scaffold proteins. These proteins contain multiple interaction domains and act as organizing platforms that recruit specific signalling components and their upstream/downstream partners to the same complex.

We focus on two classes of scaffold proteins, namely syndecan heparan sulfate proteoglycans and PDZ proteins and on one class of lipids, namely phosphoinositides. Syndecans are extracellular scaffolds and work as co-receptors for a plethora of growth factors (like FGF, Wnt, BMP) and adhesion molecules (like fibronectin, collagens). PDZ proteins are intracellular scaffolds crucial for cell polarity. PDZ domains function as protein-interaction modules that recognize short sequences at the C-terminal end of transmembrane receptors. Importantly, we found that PDZ domains can also interact with phosphoinositides, lipids that control subcellular compartmentalization and signaling events at the membrane and in the nucleus. We currently conduct 3 lines of research (i) establishing the function of syntenin-syndecan pathways in endocytosis, exocytosis, development and cancer (ii) clarifying the functional role of PDZ-lipid interaction in particular in the nucleus and (iii) unraveling how PDZ proteins integrate protein and lipid signaling at the molecular level. We thereby expect to (i) identify novel mechanisms important for development and acquired diseases, in particular cancer (ii) unravel novel aspects of the biology of PDZ proteins and contribute to a better understanding of nuclear-phosphoinositide signaling and (iii) propose novel pharmacological approaches.

Technological approaches

We combine structural, biophysical, cell biological and model organisms’ approaches. We have a quite broad expertise in standard approaches of molecular biology, cell biology (in particular fluorescence confocal and live imaging), biochemistry (in particular surface plasmon resonance/Biacore) and animal models (zebrafish and mouse). We have ongoing collaborations for NMR, crystallization, drug discovery, and cancer studies.

Figure 1

The syntenin-syndecan trafficking pathway allows a plethora of cell signaling receptor systems to escape degradation. It boosts signaling in cis (receptor recycling) and in trans (cell-cell communication via exosomes).
We are currently investigating the impact of the deregulation of this pathway in cancer signaling.
We are also trying to identify druggable compounds inhibiting this pathway.

Offre de post doctorat sur les vésicules extracellulaires

2 postes de Post-doctorants à pourvoir à partir du premier trimestre 2019: biologie moléculaire et cellulaire des vésicules extracellulaires.

Nous recrutons 2 jeunes post-doctorants intéressés par les mécanismes contrôlant la diversité moléculaire et fonctionnelle des vésicules extracellulaires. Un poste est à Paris (groupe Eric Rubinstein) et l'autre à Marseille (groupe Pascale Zimmermann). Le consortium comprend également le groupe de Clotilde Théry (Paris).

Un soutien financier est prévu pour une période maximale de 3 ans et les candidats retenus sont encouragés à obtenir une bourse indépendante (Marie-Curie, EMBO ou des organismes de financement nationaux) pendant cette période.

Une expertise en biologie cellulaire et moléculaire est indispensable, une expérience en cytométrie en flux et en microscopie à haute résolution est un atout majeur.

Les candidats motivés sont invités à postuler par courrier électronique (poste post-doc Sujet SynTEV) à et / ou

Veuillez soumettre un CV complet, un bref résumé des travaux de recherche et de l'expertise technique, ainsi que les coordonnées de deux personnes.

About the team leader

Pascale Zimmermann


  • 1995 PhD in Pharmacy, I.C.P. and Christian de Duve Institute, U.C.L., Belgium
  • 1999-2005 Post-Doctoral Fellow of the Science Foundation Flanders, Belgium
  • 2001-2002 Post-Doc, Austrian Academy of Science, Salzburg, Austria.
  • 2002-2006 V.I.B. Project leader, Belgium
  • 2006-     Research Professor K.U.Leuven, Belgium, Head Laboratory for Signal Integration in Cell Fate Decision.
  • 2011-     Directeur de Recherche Inserm, France

Scientific Awards

  • Academic Award for Fundamental Research in Medicine Period 2003-2006 (Belgium)
  • European Molecular Biology Organization (EMBO) Young Investigator Program (YIP)

Main achievements

  • Identification of the PDZ scaffold protein syntenin
  • Discovery of PDZ-lipid interactions
  • Documenting the role of vesicular trafficking in the function of heparan sulfate proteoglycans
  • Discovery of the interaction of PDZ domains with nuclear lipids