WEHI PhD Completion Seminar hosted by Professor David Komander and Dr Bekky Feltham

Philipp Schenk

PhD Student – Komander Laboratory, Ubiquitin Signalling division, WEHI

Targeting USP9X: Profiling Cancer Cell Responses to Deubiquitinase Inhibition

 

Davis Auditorium

Join via SLIDO enter code #WEHIphdcompletion

Including Q&A session

Followed by refreshments in Tapestry Lounge

The ubiquitin-proteasome system plays a central role in maintaining cellular homeostasis. Ubiquitin, a small protein modifier, is conjugated to substrate proteins, modulating a wide range of cellular processes, most notably by tagging proteins for degradation. This process is reversible through the action of deubiquitinases (DUBs), making DUB inhibition a promising strategy for targeting disease-associated substrates.

During my PhD, I studied USP9X, a DUB implicated in promoting oncogenesis across various cancer types. Despite its biological relevance, the therapeutic potential of USP9X remains underexplored, largely due to the limited availability of selective inhibitors suitable for preclinical or clinical evaluation.

My research addresses this gap through the identification and characterisation of WEHI-092, a novel small molecule inhibitor that potently and selectively inhibits USP9X over other DUBs. Using a broad range of biochemical and cell biology techniques, I have (i) investigated the binding mechanism of WEHI-092 to understand its selectivity, (ii) profiled cancer cell responses across more than 50 cell lines, (iii) gained detailed insights into USP9X biology through proteomics and ubiquitinomics approaches, and (iv) demonstrated that USP9X inhibition arrests cancer cells in metaphase.

Overall, my work advances our understanding of the cellular responses to USP9X inhibition in cancer and lays the groundwork for further exploration of USP9X as a potential clinical target.

All welcome!