Zixuan Wang

Chemistry

Zixuan Wang is a final-year PhD student in the Yusuf Hamied Department of Chemistry at the University of Cambridge, supervised by Prof. Sir Shankar Balasubramanian. Before Cambridge, she completed undergraduate training at Peking University, earning a BSc in Chemistry and a BA in Biomedical English. Her PhD research focuses on chromatin, the way DNA is packaged and regulated inside the nucleus, and on developing chemical tools to intervene in gene regulation with greater precision. This matters for cancer because many tumours rely on altered chromatin control and DNA maintenance pathways to sustain cancer-driving transcriptional programmes and to survive the stresses of rapid proliferation. Yet many chromatin-targeting drugs act broadly across the genome, which can make mechanism hard to interpret and can limit selectivity. A central theme of her thesis is to make “where a molecule acts in the genome” measurable and engineerable, so that chromatin pharmacology can be understood and potentially optimised, in a locus-aware way for disease-relevant contexts.

A major part of her thesis is the G4L-PROTAC project, which explores a new strategy to remove proteins in cancer cells by using the genome itself as a guide. These
bifunctional molecules are designed to recognise G-quadruplexes (G4s)—unusual DNA structures that are enriched in regulatory regions and frequently linked to cancer-associated gene control—and then recruit the cell’s own protein disposal machinery to degrade proteins located nearby. Instead of requiring a bespoke inhibitor for every protein target, the approach aims to localise an effector to a specific nuclear “neighbourhood” and trigger an event (protein removal) where it is most likely to matter for gene regulation. Alongside this, her thesis develops complementary genome-wide mapping approaches to measure where small molecules engage chromatin in living cells, helping to connect chemical design to mechanism and to guide future optimisation of chromatin-addressed therapies in cancer.