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Our Lab studies how changes in gene regulation affect the pathogenesis and therapy response of cancer. The goal of our research is to understand how cancer cells can respond to external stimuli and ultimately resist therapy.

Olaf Klingbeil

VIB Group Leader

Professor at KU Leuven, Department of Cellular and Molecular Medicine

 

Research focus

We investigate how specific alterations in gene regulation, including changes in signaling and transcription, impact the pathogenesis and therapeutic response of cancer. Our research aims to understand the plastic nature of cancer cells and their gene regulatory networks, which affect tumor progression and therapy response. One of the primary objectives of our studies is to identify and target the key regulators of cancer cell adaptation, to reverse or prevent therapy resistance. To achieve this, we utilize functional genomics, including the genome editing tool Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), assessing the functional significance of regulators among epigenetic, transcriptional, and signaling genes. Using CRISPR in combination with High-throughput sequencing-based methods, we can efficiently screen large sets of potential target genes in vitro and in vivo. By combining CRISPR screening with single-cell, spatial genomics, and DNA barcoding, we can track cancer cell adaptations during therapy and pinpoint the key transcriptional regulators of cell state transitions, thereby gaining a deeper understanding of adaptive resistance. These methods will help us to identify new therapeutic targets to prevent or reverse therapy resistance.

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