Abstract

One of the most fascinating hallmarks of cancer cells is their ability to evade normal differentiation and aberrantly self-renew. To maintain their aberrant identity, cancer cells strongly depend on transcription factors (TFs) and chromatin regulators that normally shape developmental processes. Pathways and co-factors controlling the dynamic expression, activity, and turnover of oncogenic TFs can provide pharmacological access to these formely “undruggable targets”, but remain poorly defined for most TFs. At the same time, a more definitive understanding of their direct regulatory functions will be crucial for drug screening and development. To meet these challenges, our lab has pioneered a simple and scalable approach combining auxin-inducible degradation (AID) and SLAM -seq that enables an unbiased analysis of direct transcriptional functions independent of mRNA and protein half-lives (Muhar et al., Science 2018). In parallel, to decipher pathways controlling the expression and turnover of TFs, we have developed a time-resolved FACS -based CRISPR screening assay that enables the systematic identification of regulatory factors independent of essential protein functions (de Almeida & Hinterndorfer et al., Nature 2021). In first studies, we have used these new tools to gain insight into the regulation and regulatory function of MYC .

Hybrid Seminar – for those external to the CRUK CI please register in advance if attending in person. Thank you.

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Zoom link: https://zoom.us/j/99749197684?pwd=V2o4VTFELzYvdVIrRlR0RTJiRjdjZz09