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Two researchers, Dr Pauline Franz and Dr Xinyuan Wu, have been awarded Marie Skłodowska-Curie Actions Postdoctoral Fellowships in the Tate research group

Dr Pauline Franz will work on developing new antibody-drug conjugates (ADCs). ADCs are an emerging class of therapeutic agents that deliver potent cytotoxic drugs to cancer cells via engineered antibodies that selectively bind cell-surface antigens. Most clinically approved ADCs use protease-cleavable linkers between the antibody and the drug, so the drug remains inactive until its cleavage by tumour-associated proteases (TAPs), enabling targeted cancer-cell killing while avoiding systemic toxicity.

Despite recent progress, the lack of specificity in current ADC linkers can cause unwanted payload release in healthy tissue, leading to toxicity, intolerable dosing, and high clinical attrition rates. Particularly for colorectal cancer (CRC), one of the leading causes of cancer-related deaths worldwide, no CRC-specific ADC has yet been approved. Pauline proposes to develop ADC(s) bearing novel TAP-selective linkers that release the drug in the tumour microenvironment of CRC. Pauline will undertake de novo discovery of novel TAP substrates directly from human patient tissue, and use these to inform the design of innovative ADC linker(s). The ADC(s) will be constructed and validated as a proof-of-concept in CRC-relevant disease models. Novel linkers developed in this proposal will provide much-needed innovation in ADC linker technology and help ensure ADCs reach their therapeutic potential in CRC. 

Dr Xinyuan Wu will work on protein degradation systems. Targeted protein degradation (TPD) via the ubiquitin-proteasome system (UPS) has emerged as a powerful therapeutic strategy. However, expanding the E3 ligase repertoire and developing novel degraders remain critical frontiers for future development.

Xinyuan will focus on developing degraders from novel E3 ligase covalent ligands discovered through platforms integrating covalent DNA-encoded library (CoDEL) selection with proteomics, molecular biology assays, and other advanced technologies, aiming to tackle targets challenging to degrade through CRBN- or VHL- based degraders. These platforms will also be able to be extended to other chemically induced proximity (CIP) applications.

Congratulations to both for these prestigious funding awards!