Piet Borst
(Group leader)

Multidrug resistance of cancer cells

We are interested in the mechanisms that underlie drug resistance in cancer cells and focus on resistance caused by increased ATP-dependent transport of drug out of the cell, mediated by ATP-binding cassette (ABC) transporters. We have isolated genes for these transporters and are characterizing their substrate specificity and sensitivity to inhibitors in transfected cells. We are also studying resistance mechanisms in spontaneous tumors arising in genetically modified mice.

DNA base J

A second focus is DNA base J. This work is an offshoot of our long-standing interest in the mechanisms of antigenic variation in African trypanosomes. DNA base J (or β-glucosyl-hydroxymethyluracil) is a base present in all kinetoplastid flagellates including the pathogenic ones, such as trypanosomes and Leishmania species. Base J replaces 1% of thymine in DNA and is predominantly located in repetitive sequences, such as telomeric repeats. Removing J from these locations results in massive readthrough of RNA polymerase II transcription, which is likely to kill the Leishmania.

For further information check out our research pages.

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