During his PhD studies, Huijie Yuan investigated O-GlcNAc, a unique and dynamic protein modification essential for life and tightly linked to numerous diseases, from neurodegeneration to cancer. Too little O-GlcNAc is observed in Alzheimer’s and Parkinson’s disease, while too much is seen in diabetes and many cancers, making it a compelling but underexplored therapeutic target. 

In his PhD, he developed the first high-throughput, cell-based platform to screen OGT variants associated with intellectual disability (OGT-CDG), revealing that disruption of O-GlcNAc homeostasis is a common feature among pathogenic variants. Using this system, he repurposed lovastatin, a widely prescribed cholesterol-lowering drug, as a modulator that elevates O-GlcNAc levels, suggesting potential therapeutic applications for diseases linked to O-GlcNAc deficiency. To further probe O-GlcNAc regulation, he engineered a multiplexed, triple-fluorescent cell system that enables simultaneous high-throughput quantification of OGT, OGA, and O-GlcNAc levels within single cells. This platform was further adapted for genome-wide CRISPR screening to uncover key genetic regulators of O-GlcNAc homeostasis. 

Together, this work provides powerful new tools for dissecting O-GlcNAc biology and establishes a framework for developing diagnostic and therapeutic strategies targeting this critical cellular pathway, advancing our understanding of both normal and pathogenic O-GlcNAc homeostasis.

The PhD degree will be awarded by the University of Dundee, and the defence will take place at the Department of Molecular Biology and Genetics, Aarhus University.

Time: Thursday, 18 December 2025 at 13:00
Place: Building 1871, room 120, Lecture Theatre Nucleus, Department of Molecular Biology and Genetics, Aarhus University, Universitetsbyen 81, 8000 Aarhus C
Title of PhD thesis: Dissecting normal and pathogenic O-GlcNAc homeostasis

Members of the assessment committee:

• Dr. Greg Findlay, University of Dundee, UK

• Dr. Stephanie Olivier-van Stichelen, Medical College of Wisconsin, USA

• Acting chair: Professor Daan van Aalten, Department of Molecular Biology and Genetics, Aarhus University, Denmark

Main supervisor: Professor Daan van Aalten, Department of Molecular Biology and Genetics, Aarhus University, Denmark

Language: The PhD dissertation will be defended in English.

The defence is public.

Because the degree is issued by the University of Dundee, the PhD thesis is not available through GSNS.