Hosted by Cardiff University's School of Medicine
We have made the unexpected discovery that bystander cells release citrullinated chromatin to the extracellular space, in a process akin to Neutrophil Extracellular Traps. Blocking of extracellular chromatin components reduces reprogramming, as does pharmacological interference with extracellular DNA- and histone-sensing, innate immunity signalling pathways. Our data suggest that cells that “fail” to reprogramme in fact have an active role in supporting the establishment of pluripotency. Additionally, they open a new research avenue into the study of extracellular chromatin as a cell communication mechanism that mediates cell fate transitions and present an opportunity to exploit this mechanism to enhance reprogramming and regeneration while minimizing genetic manipulation.
- Non-cell-autonomous mechanisms in cell reprograming and tissue regeneration
- The role of the protein PADI4
- Extracellular chromatin as a cell communication mechanism
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Dr Maria Christophorou is a group leader within the Babraham Institute. Her research uses biochemistry, cell and molecular biology and mouse model systems to understand the mechanisms that modulate the function of epigenetic regulators, how these mechanisms are perturbed in disease and how they may be targeted for therapeutic effect. Maria’s research on post-translational modifications investigates how these fine-tune protein function by determining when, where and how proteins work, focussing on the largely unexplored protein modification of citrullination. Abnormal citrullination is a feature of autoimmune diseases, neurodegeneration, atherosclerosis and cancer.
She did her PhD at the University of California, San Francisco, where she dissected the relative contributions of different p53 activating signals towards tumour suppression using mouse models of conditional p53 perturbation. After a fruitful decade in the US, she returned to Europe to work at the Gurdon Institute, University of Cambridge. Her work there uncovered a novel role for the peptidylarginine deiminase PADI4 in the regulation of pluripotency and a molecular mechanism by which PADI4 regulates chromatin condensation.
Maria started her independent research career at the MRC Human Genetics Unit, University of Edinburgh in 2015 as a Chancellor’s fellow. She has been a Sir Henry Dale fellow, funded by the Wellcome Trust and Royal Society, since 2015. She was awarded the Wellcome-Beit Prize in December 2014.