Contact details:

[email protected]
+44 2032 394843

University of Plymouth
Faculty of Health
Derriford Research Facility
Plymouth, PL6 8BU

Research interests:

Our main research interest is using cancer genomes as a tool to understand tumour evolution and from this devise novel avenues for therapy. We do this using a combination of cancer informatics, comparative genomics and mouse models.

We have previously performed forward genetic screens in mice using insertion mutations that deregulate or disrupt transcripts, eventually giving rise to lymphoid malignancies. From these screens we identified hundreds of loci undergoing selection during lymphomagenesis many of which are also observed in human malignancies.

Early mutations in tumour development are “clonal” i.e. present in the majority of the tumour whereas later mutations are subclonal and may be present in only a small fraction of tumour cells. We have seen that early clonal mutations greatly affect the spectrum of subsequent mutations selected at other loci. Subclonal mutations present in patients at the time of first treatment are frequently responsible for resistance and relapse. As such being able to predict which subclonal mutations are present in tumours has implications for choosing appropriate therapies.

Our current efforts are refining methods for analysing subclonal mutations in tumour cohorts and validating mutated genes as therapeutic targets in primary lymphoma cultures and mouse models.

Selected publications:

Dawes JC. Uren AG
Forward and reverse genetics of B cell malignancies: from insertional mutagenesis to CRISPR-Cas9. (Review)
Frontiers in Immunology 2021 12:670280 DOI

Guerrero A. Guiho R. Herranz N. Uren AG. Withers DJ. Martínez-Barbera JP. Tietze L. Gil J.
Duocarmycin galactose-modified prodrugs as senolytics.
Aging Cell 2020 19(4):e13133 DOI

*Dawes JC. *Webster P. *Iadarola B. *Garcia-Diaz C. Dore M. Bolt BJ. Dewchand H. Dharmalingam G. McLatchie AP. Kaczor J. Caceres JJ. Paccanaro A. Laurence L. Parrinello S. Uren AG.
LUMI-PCR: an Illumina platform ligation-mediated PCR protocol for integration site cloning, provides molecular quantitation of integration sites.
Mobile DNA 2020 11(7) DOI

Guerrero A. Herranz N. Sun B. Wagner V. Gallage S. Guiho R. Wolter K. Pombo J. Irvine E. Innes AJ. Birch J. Glegola J. Manshaei S. Heide D. Dharmalingam G. Harbig J. Olona A. Behmoaras J. Dauch D. Uren AG. Zender L. Vernia S. Martínez-Barbera JP. Heikenwalder M. Withers DJ. Gil J.
Cardiac glycosides are broad-spectrum senolytics.
Nature Metabolism 2019 1:1074–1088 DOI

*Webster P. *Dawes JC. Dewchand H. Takacs K. Iadarola B. Bolt BJ. Caceres JJ. Kaczor J. Game L. Adejumo T. Elliott J. Naresh K. Karimi M. Rekopoulou K. Tan G. Dharmalingam G. Paccanaro A. Uren AG.
Subclonal mutation selection in mouse lymphomagenesis identifies known cancer loci and suggests novel candidates.
Nature Communications 2018 9(1):2649. DOI