Zhu Liang
DPhil student in Clinical Medicine
Role of ubiquitination in regulating the NLRP3 inflammosome
The inflammasome is an essential protein complex within the innate immune system. It drives the production of the pro-inflammatory cytokine interleukin-1β (IL-1β) through caspase-1 dependent signalling pathway. The NOD-, LRR-, and Pyrin domain-containing 3 (NLRP3) inflammasome can detect a wide range of microbial or non-microbial stimuli, including PAMPs and DAMPs, and it has been associated with neurodegenerative disease (1). Understanding the regulation of the NLRP3 inflammasome is therefore emerging as a major therapeutic strategy for preventing neurodegeneration, memory loss and disease (2).
The main objective of my DPhil Project is to use chemoproteomics and ubiquitomics tools to identify key components of the ubiquitination system that regulate neuroinflammation. This will initially focus on a proteomics approach using mass spectrometry and ubiquitin-based active site probes to discover deubiquitylating enzymes (DUBs) involved in formation of the ‘inflammasome’. Once these proteins have been identified, genetic and functional studies will be performed in collaboration with the Oxford Drug Discovery Institute. This will utilize primary rodent cells and human cellular models derived from induced pluripotent stem cells (iPSC) to understand the role of these proteins in regulating microglial activation and neuro-inflammation.
References:
1. Swanson, Karen V., Meng Deng, and Jenny P-Y. Ting. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nature Reviews Immunology, 2019
2. Heneka, MT., Róisín M. McManus, and Eicke Latz. Inflammasome signalling in brain function and neurodegenerative disease. Nature Reviews Neuroscience, 2018
Recent publications
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Inflammasome activation controlled by the interplay between post-translational modifications: emerging drug target opportunities
Journal article
Liang Z. et al, (2021), Cell Communication and Signaling, 19
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Herbal decoctosome is a novel form of medicine
Journal article
Li X. et al, (2019), Science China Life Sciences, 62, 333 - 348
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Large-scale analysis of small RNAs derived from traditional Chinese herbs in human tissues
Journal article
Huang F. et al, (2019), Science China Life Sciences, 62, 321 - 332
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Plant-derived phosphocholine facilitates cellular uptake of anti-pulmonary fibrotic HJT-sRNA-m7
Journal article
Du J. et al, (2019), Science China Life Sciences, 62, 309 - 320
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Neuraminidase of Influenza A Virus Binds Lysosome-Associated Membrane Proteins Directly and Induces Lysosome Rupture
Journal article
Ju X. et al, (2015), Journal of Virology, 89, 10347 - 10358
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Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections
Journal article
Zou Z. et al, (2014), Nature Communications, 5
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Autophagy in tumorigenesis and cancer therapy: Dr. Jekyll or Mr. Hyde?
Journal article
Zhou S. et al, (2012), Cancer letters, 323, 115 - 127