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Full NameDr Lisa Crawford
Queen's University Belfast
Multiple Myeloma (MM) is characterised by the clonal proliferation of plasma cells and excess production of non-functional immunoglobulins, making this malignancy particularly vulnerable to interference with protein handling pathways. The ubiquitin proteasome pathway (UPP) is at the core of cellular protein homeostasis and strategies targeting both specific and bulk protein degradation through this pathway, using IMiDs and proteasome inhibitors, form the backbone of MM therapy. While these therapies have contributed to improved survival rates, emergence of resistance to all currently available therapies is a major clinical challenge. The major focus of our lab is to explore the molecular mechanisms involved in dysregulation of the ubiquitin proteasome system in MM, particularly E3 ligases, and apply this knowledge to identify novel therapeutic opportunities to augment the efficacy or overcome resistance to current therapies. Using a combination of genomic and proteomic approaches, we are currently investigating the role of two E3 ligases in promoting increased genomic instability in MM and exploring strategies to therapeutically exploit related vulnerabilities in specific patient subgroups.