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Cell Biology I: Wouter Moolenaar

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Wouter Moolenaar, Ph.D. professorGroup leader, professor

About Wouter Moolenaar

Lipid Growth Factor Signaling

The Autotaxin-LPA Signaling Axis
LPA is an extracellular signaling molecule that acts through multiple G protein-coupled receptors present in numerous cell types.LPA receptor signaling is implicated in a wide variety of physiological and pathological processes, ranging from vascular development to metastasis. The classical LPA receptors stimulate cell migration and proliferation, and are implicated in cell transformation and metastasis. Newly identified LPA receptors can mediate inhibitory responses, which renders the global LPA signaling picture increasingly complex. One challenge is to understand how distinct LPA receptors cooperate, to predict the biological outcome of LPA stimulation in a given cell type.
 
Autotaxin
Autotaxin (ATX) is the major LPA-producing enzyme in plasma and tissues. We are analyzing the function of autotaxin using multiple approaches, including structural studies and the development of mouse models and small-molecule inhibitors. The knockout mouse revealed an unexpected function for ATX in vascular development. Furthermore, the structure of ATX revealed novel features, notably the presence of a deep lipid-binding pocket and a nearby open tunnel, which we are now further investigating (collaboration A. Perrakis). Our studies have provided new insights into the mode of action of ATX, and how it delivers LPA to target cells. Targeting the ATX-LPA signaling axis may prove a valuable strategy for inhibiting tumor cell growth and metastasis.

Co-workers

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Elisabetta Argenzio

Postdoctoral fellow

Experience

I received my PhD at the European School of Molecular Medicine in Milan (Italy), particularly focusing on molecular oncology. Since 2009, I have been working as a postdoctoral fellow at the NKI.

The Moolenaar lab recently discovered that LPA-induced RhoA activation leads to a rapid and reversible recruitment of the Chloride Intracellular Channel 4 (CLIC4) protein to the plasma membrane. My goal is to elucidate the biological function of CLIC4 as a novel player in Rho signaling and intracellular trafficking. I am addressing this issue by using biochemical assays and imaging techniques.

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Elisa Matas Rico

Postdoctoral fellow

Experience

I received my PhD from the University of Málaga (Spain),  where I characterized the neurophysiological abnormalities in LPA1 receptor knockout mice. Since 2010, I am working as a postdoctoral fellow in the Moolenaar lab at the NKI.

My project focuses on the role of a transmembrane exo-phosphodiesterase, termed GDE2, in the morphological differentiation of neuroblastoma cells. We discovered that GDE2 expression leads to altered neuronal morphology and attenuates LPA signaling. My goal is to elucidate how GDE2 expression intersects with LPA signaling to promote neuroblastoma differentiation.     

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Michiel van Veen

Ph.D. student

Experience

I studied Medical Pharmaceutical Science at Groningen University and started my PhD studies at the NKI in 2011. I was trained in pharmacodynamics and kinetics, but wanted to learn more about cell signaling and cancer cell biology. I worked as an udergraduate in the Moolenaar lab during my final internship, and then continued as a PhD student.

My project focuses on elucidating the role of a transmembrane exo-phospholipase in the differentiation of neuroblastoma cells. To this end, I use a great variety of techniques including protein purification and crystallization, fluorescence microscopy (FRET/FLIM), lipid analysis and enzyme activity assays.

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Key publications View All Publications

  • Structural basis of substrate discrimination and integrin binding by autotaxin

    Nat Struct Mol Biol. 2011; 18: 198-204

    Hausmann J, Kamtekar S, Christodoulou E, Day JE, Wu T, Fulkerson Z, Albers HM, van Meeteren LA, Houben AJ, van Zeijl L, Jansen S, Andries et al.

    Link to PubMed
  • Autotaxin: structure-function and signaling.

    J Lipid Res. 2014 Feb 18;55(6):1010-1018. [Epub ahead of print]

    Perrakis A, Moolenaar WH.

    Link to PubMed
 
 

Recent publications View All Publications

  • Neuronal differentiation through GPI-anchor cleavage.

    Cell Cycle. 2017 Mar 4;16(5):388-389

    Matas-Rico E, van Veen M, Moolenaar WH.

    Link to Pubmed
  • GDE2/GDPD5 in neuroblastoma.

    Oncotarget. 2017 Jan 24;8(4):5672-5673.

    Matas-Rico E, van Veen M, Moolenaar WH.

    Link to PubMed
 

Contact

  • Office manager

    Mariet van den Berg

  • E-mail

    ma.vd.berg@nki.nl

  • Telephone Number

    +31 20 512 9184

Van den Berg, Mariet

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