Research in the Lansdorp lab is aimed at understanding the role of stem cells in relation to ageing. The focus is on the role of telomeres and telomerase in stem cell renewal, the role of specific helicases and specific DNA sequences in stem cell function and, more generally, on the molecular mechanisms that regulate stem cell self-renewal and differentiation. Key questions are related to the role of (epi-)genetic instability in ageing, chromatin differences between mortal and immortal stem cells and the role guanine quadruplex structures in nuclear organization and chromosome instability.
Scientific Director, Group Leader of the Laboratory of Genetic Instability, Ageing and Cancer
Stem cells, telomere biology, genome stability and cancer
We have developed novel techniques including single cell DNA (strand) sequencing techniques that allow accurate identification of numerical chromosomal abnormalities and specific sister chromatids in individual cells. For studies of telomere attrition and numerical chromosomal abnormalities in aging specific cells are analysed by flow cytometry and sorted as single cells. Such cells include cells from participants in the LifeLines project in Groningen (160,000 individuals). Studies of human cells are complemented using cells from patients and studies in suitable mouse models. We are specifically interested to measure telomere dysfunction and aneuploidy in stem cells and more differentiated cell types, to identify genetic and other factors regulating human leukocyte telomere length and to study the role of genetic instability and chromosomal abnormalities in cells in relation to normal human ageing and specific diseases.
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