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Exploring the consequences of nuclear envolope stress in cancer cells.

Altered nuclear shape is a defining feature of cancer cells, but the relationship with pathology development remains elusive. Recent observations indicate that nuclear dysmorphy correlates with an enhanced propensity of nuclei to rupture. Such ruptures transiently perturb nuclear compartmentalization but also provoke DNA damage. Thus, nuclear dysmorphy and fragility – jointly referred to as nuclear envelope (NE) stress – may contribute to genome instability and thereby represent a novel emerging hallmark of cancer. To better understand the contribution of NE stress to the carcinogenic process, I propose to systematically investigate the short- and long-term molecular consequences. To this end, I intend to analyze the population-level changes in the transcriptome as well as in the genome upon targeted, temporary disruption of nuclear compartmentalisation. This way, I expect to generate a comprehensive view on the impact of NE stress on cell fate. In extensu, this work may also lead to the identification of novel synthetic lethal targets that could be exploited in clinical applications.
Date:1 Jan 2019 →  31 Dec 2021
Disciplines:Cytoskeleton, Intracellular compartments and transport, Genomics, Transcriptomics, Biomedical image processing, Cancer biology