Roy G. H. P. van Heesbeen

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Wnt proteins are lipid-modified glycoproteins that play a central role in development, adult tissue homeostasis and disease. Secretion of Wnt proteins is mediated by the Wnt-binding protein Wntless (Wls), which transports Wnt from the Golgi network to the cell surface for release. It has recently been shown that recycling of Wls through a retromer-dependent(More)
The microtubule motor protein kinesin-5 (Eg5) provides an outward force on centrosomes, which drives bipolar spindle assembly. Acute inhibition of Eg5 blocks centrosome separation and causes mitotic arrest in human cells, making Eg5 an attractive target for anti-cancer therapy. Using in vitro directed evolution, we show that human cells treated with Eg5(More)
Eg5 (kinesin-5) is a highly conserved microtubule motor protein, essential for centrosome separation and bipolar spindle assembly in human cells. Using an "in vitro" evolution approach, we generated human cancer cells that can grow in the complete absence of Eg5 activity. Characterization of these Eg5-independent cells (EICs) led to the identification of a(More)
Bipolar spindle assembly requires force to organize the microtubule network. Here, we show that three motor proteins, namely Eg5, Kif15, and dynein, act together to produce the right force balance in the spindle. Excessive inward force results in monopolar spindle formation, while excessive outward force generation results in unstable spindles with splayed(More)
A missense mutation in mouse Nek8, which encodes a ciliary kinase, produces the juvenile cystic kidneys (jck) model of polycystic kidney disease, but the functions of Nek8 are incompletely understood. Here, we generated a Nek8-null allele and found that homozygous mutant mice die at birth and exhibit randomization of left-right asymmetry, cardiac anomalies,(More)
Inhibition of the microtubule (MT) motor protein Eg5 results in a mitotic arrest due to the formation of monopolar spindles, making Eg5 an attractive target for anti-cancer therapies. However, Eg5-independent pathways for bipolar spindle formation exist, which might promote resistance to treatment with Eg5 inhibitors. To identify essential components for(More)
High-content screening (HCS) can generate large multidimensional datasets and when aligned with the appropriate data mining tools, it can yield valuable insights into the mechanism of action of bioactive molecules. However, easy-to-use data mining tools are not widely available, with the result that these datasets are frequently underutilized. Here, we(More)
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