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Investigating the effects of arginine methylation inhibitors on microdissected brain tumour biopsies maintained in a miniaturised perfusion system

Barry, Antonia; Samuel, Sabrina F.; Hosni, Ines; Moursi, Amr; Feugere, Lauric; Sennett, Christopher J.; Deepak, Srihari; Achawal, Shailendra; Rajaraman, Chittoor; Iles, Alexander; Wollenberg Valero, Katharina C.; Scott, Ian S.; Green, Vicky; Stead, Lucy F.; Greenman, John; Wade, Mark A.; Beltran-Alvarez, Pedro


Antonia Barry

Sabrina F. Samuel

Ines Hosni

Amr Moursi

Lauric Feugere

Christopher J. Sennett

Srihari Deepak

Shailendra Achawal

Chittoor Rajaraman

Alexander Iles

Katharina C. Wollenberg Valero

Ian S. Scott

Lucy F. Stead

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Dr Mark Wade
Senior Lecturer in Molecular Genetics

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Dr Pedro Beltran-Alvarez
Senior Lecturer in Health and Climate Change and Programme co-Director of the MSc Health and Climate Change


Arginine methylation is a post-translational modification that consists of the transfer of one or two methyl (CH3) groups to arginine residues in proteins. Several types of arginine methylation occur, namely monomethylation, symmetric dimethylation and asymmetric dimethylation, which are catalysed by different protein arginine methyltransferases (PRMTs). Inhibitors of PRMTs have recently entered clinical trials to target several types of cancer, including gliomas (NCT04089449). People with glioblastoma (GBM), the most aggressive form of brain tumour, are among those with the poorest quality of life and likelihood of survival of anyone diagnosed with cancer. There is currently a lack of (pre)clinical research on the possible application of PRMT inhibitors to target brain tumours. Here, we set out to investigate the effects of clinically-relevant PRMT inhibitors on GBM biopsies. We present a new, low-cost, easy to fabricate perfusion device that can maintain GBM tissue in a viable condition for at least eight days post-surgical resection. The miniaturised perfusion device enables the treatment of GBM tissue with PRMT inhibitors ex vivo, and we observed a two-fold increase in apoptosis in treated samples compared to parallel control experiments. Mechanistically, we show thousands of differentially expressed genes after treatment, and changes in the type of arginine methylation of the RNA binding protein FUS that are consistent with hundreds of differential gene splicing events. This is the first time that cross-talk between different types of arginine methylation has been observed in clinical samples after treatment with PRMT inhibitors.


Barry, A., Samuel, S. F., Hosni, I., Moursi, A., Feugere, L., Sennett, C. J., …Beltran-Alvarez, P. (2023). Investigating the effects of arginine methylation inhibitors on microdissected brain tumour biopsies maintained in a miniaturised perfusion system. Lab on a chip, 23(11), 2664-2682.

Journal Article Type Article
Acceptance Date May 3, 2023
Online Publication Date May 3, 2023
Publication Date Jun 7, 2023
Deposit Date May 3, 2023
Publicly Available Date Jun 2, 2023
Journal Lab on a Chip
Print ISSN 1473-0197
Electronic ISSN 1473-0189
Publisher Royal Society of Chemistry
Peer Reviewed Peer Reviewed
Volume 23
Issue 11
Pages 2664-2682
Public URL


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