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New FFG-Project launched by Florian Grebien

Jessica Ebner will taget WDR5

Seeking to exploit some of his recent discoveries Florian Grebien now launched a new project in cooperation with CeMM and the Structural Genomics Consortium, Toronto, Canada. With the financial support of the FFG "Industrianahe Dissertationen" PhD student Jessica Ebner will aim to target the epigenetic regulator WDR5 with an innovative approach.

Dysfunctional epigenetic pathways contribute to many pathologies and also during tumorigenesis they are often mutated or de-regulated. In particular, leukaemias were shown to require the MLL complex. Various cancers exhibit strong dependence on the protein WDR5 and forced down-regulation of WDR5 is sufficient to block tumour growth. To pharmacologically interfere with WDR5 function, we have recently characterized the first-in-class small molecule WDR5 antagonist. It disrupts the interaction of WDR5 with MLL, thereby inactivating this protein complex. This result in strong anti-proliferative effects and restored differentiation potential in leukaemia cells. Hence, we could provide a proof-of-concept for small-molecule-mediated targeting of WDR5, which might represent an attractive therapeutic strategy to target leukaemia cells.

Within the FFG project entitled "Pharmacological WDR5 degradation" PhD student Jessica Ebner will explore innovative approaches to inactivate WDR5 by targeting it specifically for degradation.