O-GlcNAcylation and Its Role in Cancer-Associated Inflammation

Apr 1, 2022·
Muzi Ouyang (Mia)
Muzi Ouyang (Mia)
,
Changmeng Yu
,
Xiaolian Deng
,
Yingyi Zhang
,
Xudong Zhang
,
Fangfang Duan
· 0 min read
DOI
Abstract
Cancer cells, as well as surrounding stromal and inflammatory cells, form an inflammatory tumor microenvironment (TME) to promote all stages of carcinogenesis. As an emerging post- translational modification (PTM) of serine and threonine residues of proteins, O-linked-N- Acetylglucosaminylation (O-GlcNAcylation) regulates diverse cancer-relevant processes, such as signal transduction, transcription, cell division, metabolism and cytoskeletal regulation. Recent studies suggest that O-GlcNAcylation regulates the development, maturation and functions of immune cells. However, the role of protein O-GlcNAcylation in cancer-associated inflammation has been less explored. This review summarizes the current understanding of the influence of protein O-GlcNAcylation on cancer-associated inflammation and the mechanisms whereby O-GlcNAc-mediated inflammation regulates tumor progression. This will provide a theoretical basis for further development of anti-cancer therapies.
Type
Publication
Frontiers in Immunology, 13, 861559
Status
Peer-reviewed Open access
publications
Muzi Ouyang (Mia)
Authors
PhD Candidate

I am Muzi Ouyang (欧阳木子) — I go by Mia. I am a PhD candidate in Chemistry at Tsinghua University, advised by Prof. Ying Tan (谭英) at the Institute of Biopharmaceutical and Health Engineering (iBHE) in Shenzhen. I work on targeted protein degradation: designing bioPROTACs that recruit E3 ligases to destroy proteins small molecules struggle to drug — and working out why that degradation sometimes fails.

My dissertation has two halves. The first is a dual-target bioPROTAC that co-degrades ERα and PI3K p85α, re-sensitizing tamoxifen-resistant breast cancer cells to endocrine therapy. The second is a KRAS-targeting degrader, where I found a resistance mutation in the hypervariable region that lets KRAS escape a multimerization-dependent platform, and used all-atom molecular dynamics to trace the conformational mechanism behind the escape.

Alongside the wet lab I work in computational protein design — Rosetta, ProteinMPNN and AlphaFold2 — including an end-to-end reproduction of the CLAIRE de novo binder-design pipeline, published openly with its debugging narrative. My training spans animal science, basic medicine and chemistry, which is why I move between wet-lab mechanism and computational design rather than choosing between them.

I expect to defend in June 2027 and am seeking postdoctoral positions starting in late 2027. If my work overlaps with your group’s, I’d be glad to hear from you — I’ll gladly send my CV. Write to me at mumumia.1009@gmail.com, or oymzmia@163.com if you are corresponding from within China.