Seminar

Targeted protein degradation: genetic determinants and drug discovery opportunities

Cristina Mayor-Ruiz

Targeted protein degradation is a new therapeutic modality based on drugs that destabilize proteins by inducing their proximity to E3 ubiquitin ligases. Of particular interest are "molecular glue degraders": compounds that can degrade otherwise undruggable proteins by orchestrating direct interactions between protein target and E3. However, their discovery has been serendipitous, thus hampering broad translational efforts. I will present a scalable target-agnostic strategy toward glue degrader discovery. This approach is based on differential chemical screening coupled to a multi-omics target deconvolution campaign. Collectively, our data outline a versatile and broadly applicable strategy to identify degraders and thus empower future drug discovery efforts Biosketch Cristina Mayor-Ruiz obtained her PhD in 2017 at the CNIO (Madrid) under the supervision of Óscar Fernández-Capetillo. There, she explored mechanisms of resistance to anticancer therapies. In 2018, she joined the group of Georg Winter at CeMM (Vienna) supported by EMBO and Marie Curie postdoctoral fellowships, where her interests focused on different aspects of chemical biology and drug screening. Since January 2021, she leads the “Targeted Protein Degradation & Drug discovery” lab at IRB Barcelona. Her research focuses on: (1) Developing screening strategies for early drug discovery. In particular, to develop monovalent degraders and other proximity-inducing drugs with therapeutic interest. (2) Tackling exciting biological questions that either benefit from the high kinetic resolution provided by targeted protein degradation, or that involve E3 (dys)regulation dynamics