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May 15, 2026
Yuan Zhao, Pharmsci graduate student (Tang Lab), will be defending her PhD research thesis:
Development of Targeted Molecular Platforms for Therapeutic Applications: Extracellular Protein Degradation and Antibody Conjugation
Abstract:
Targeted protein degradation degrade disease-associated proteins by recruiting endogenous degradation pathways. While many current degrader technologies act through the intracellular ubiquitin-proteasome system, extracellular and membrane-associated proteins require alternative strategies that use endocytosis and lysosomal trafficking. This dissertation focuses on the development of molecular platforms for lysosome-based extracellular protein degradation and antibody conjugation. It describes LRP1-recruiting degraders with potential relevance to blood-brain barrier-associated delivery, IGF2R-recruiting platforms designed to improve recruiter selectivity or simplify ligand structure, and a glycosite-specific antibody conjugation strategy for preparing more homogeneous antibody-drug and degrader-antibody conjugates. Together, these studies expand the platform toolkit for extracellular targeted protein degradation and support the design of more defined therapeutic conjugates.