Dr Anthony Uren
Profiles

Dr Anthony Uren

Lecturer in Biomedical Sciences (Blood Science)

School of Biomedical Sciences (Faculty of Health)

Research

Research

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.

Publications

Publications

Journals

Van de Pette M. Dimond A. Galvão AM. Millership SJ. To W. Prodani C. McNamara G, Bruno L. Sardini A. Webster Z. McGinty J. French, PMW. Uren AG. Castillo-Fernandez J. Watkinson W. Ferguson-Smith AC. Merkenschlager M. John RM. Kelsey G. Fisher AG. (2022) Epigenetic changes induced by in utero dietary challenge result in phenotypic variability in successive generations of mice.
Nature Communications 13(1) 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

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

*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)

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

*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.

Van de Pette M. Abbas A. Feytout A. McNamara G. Bruno L. To WK. Dimond A. Sardini A. Webster Z. McGinty J. Paul EJ. Ungless MA. French PM. Withers DJ. Uren A. Ferguson-Smith AC. Merkenschlager M. John RM. Fisher AG.
Visualizing Changes in Cdkn1c Expression Links Early-Life Adversity to Imprint Mis-regulation in Adults.
Cell Reports 2017 18(5):1090-1099.

Curry E. Green I. Chapman-Rothe N. Shamsaei E. Kandil S. Cherblanc FL. Payne L. Bell E. Ganesh T. Srimongkolpithak N. Caron J. Li F. Uren AG. Snyder JP. Vedadi M. Fuchter MJ. Brown R.
Dual EZH2 and EHMT2 histone methyltransferase inhibition increases biological efficacy in breast cancer cells.
Clinical Epigenetics 2015 7(1): 84.

de Ridder J. Kool J. Uren AG. Bot J. de Jong J. Rust AG. Berns A. van Lohuizen M. Adams DJ. Wessels L. Reinders M.
Mutational Genomics for Cancer Pathway Discovery
Lecture Notes in Computer Science 2013 7986:35-46

Westerman BA. Blom M. Tanger E. van der Valk M Song JY. van Santen M. Gadiot J. Cornelissen-Steijger P. Zevenhoven J. Prosser HM. Uren A. Aronica E. van Lohuizen M.
GFAP-Cre-mediated transgenic activation of Bmi1 results in pituitary tumors.
PLoS One 2012 7(5):e35943

March HN. Rust AG. Wright NA. ten Hoeve J. de Ridder J. Eldridge M. van der Weyden L. Berns A. Gadiot J. Uren A. Kemp R. Arends MJ. Wessels LF. Winton DJ. Adams DJ.
Insertional mutagenesis identifies multiple networks of cooperating genes driving intestinal tumorigenesis.
Nature Genetics 2011 43(12):1202-1209

Vassiliou GS. Cooper JL. Rad R. Li J. Rice S. Uren A. Rad L. Ellis P. Andrews R. Banerjee R. Grove C. Wang W. Liu P. Wright P. Arends M. Bradley A.
Mutant nucleophosmin and cooperating pathways drive leukemia initiation and progression in mice.
Nature Genetics 2011 43(5):470-475

*Kool J. *Uren AG. Martins CP. Sie D. de Ridder J. Turner G. van Uitert M. Matentzoglu K. Lagcher W. Krimpenfort P. Gadiot J. Pritchard C. Lenz J. Lund AH. Jonkers J. Rogers J. Adams DJ. Wessels L Berns A van Lohuizen M.
Insertional mutagenesis in mice deficient for p15Ink4b p16Ink4a p21Cip1 and p27Kip1 reveals cancer gene interactions and correlations with tumor phenotypes.
Cancer Research 2010 70(2):520-531

Mattison J. Kool J. Uren AG. de Ridder J. Wessels L. Jonkers J. Bignell GR. Butler A. Rust AG. Brosch M. Wilson CH. van der Weyden L. Largaespada DA. Stratton MR. Futreal PA. van Lohuizen M. Berns A. Collier LS. Hubbard T. Adams DJ.
Novel candidate cancer genes identified by a large-scale cross-species comparative oncogenomics approach.
Cancer Research 2010 70(3):883-895

Uren AG. Berns A.
Jump-starting cancer gene discovery (News & Views article)
Nature Biotechnology 2009 27(3):251-252

*Uren AG. *Mikkers H. Kool J. van der Weyden L. Lund A.H. Wilson CH. Rance R. Jonkers J. van Lohuizen M. Berns A. Adams DJ.
A high-throughput splinkerette-PCR method for the isolation and sequencing of retroviral insertion sites.
Nature Protocols 2009 4(5):789-798

Csikós T. Reijmers RM. Uren AG. Spaargaren M. Pals ST.
Instant conditional transgenesis in the mouse hematopoietic compartment.
J Immunol Methods 2008 339(2):259-263

*Uren AG. *Kool J. Matentzoglu K. de Ridder J. Mattison J. van Uitert M. Lagcher W. Sie D. Tanger E. Cox T. Reinders M. Hubbard TJ. Rogers J. Jonkers J. Wessels L. Adams D.J. van Lohuizen M. Berns A.
Large scale mutagenesis in p19ARF and p53 deficient mice identifies cancer genes and their collaborative networks.
Cell 2008 133(4):727-41

De Ridder J. Kool J. Uren A. Bot J. Wessels L. Reinders M.
Co-occurrence analysis of insertional mutagenesis data reveals cooperating oncogenes.
Bioinformatics 2007 23(13):i133-41

De Ridder J. Uren A. Kool J. Reinders M. Wessels L.
Detecting statistically significant common insertion sites in retroviral insertional mutagenesis screens.
Plos Computational Biology 2006 2(12): e166

*Uren AG. *Kool J. Berns A. van Lohuizen M.
Retroviral insertional mutagenesis: past present and future. (Review)
Oncogene 2005 24(52):7656-7672

Uren AG. O'Rourke K. Aravind L. Pisabarro MT. Seshagiri S. Koonin EV. Dixit VM.
Identification of Paracaspases and Metacaspases: Two ancient families of caspase-like proteins one of which plays a key role in MALT lymphoma.
Molecular Cell 2000 6(4):961-967

*Uren AG. *Wong L. Pakusch M. Fowler K. Burrows FJ. Vaux DL. Choo KHA.
Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype
Current Biology 2000 10(21):1319-1328

Speliotes EK. Uren A. Vaux D. Horvitz H.R.
The survivin-like C. elegans BIR-1 protein acts with the aurora-like kinase AIR-2 to affect chromosomes and the spindle midzone.
Molecular Cell 2000 6(2):211-223

Uren AG. Beilharz T. O'Connell MJ. Bugg SJ. van Driel R. Vaux DL. Lithgow T.
Role for yeast inhibitor of apoptosis (IAP)-like proteins in cell division.
P.N.A.S. 1999 96(18):10170-10175

Hawkins CJ. Ekert PG. Uren AG. Holmgreen SP. Vaux DL.
Anti-Apoptotic potential of insect cellular and viral IAPs in mammalian cells.
Cell Death & Differentiation 1998 5(7):569-576

Uren AG. Coulson EJ. Vaux DL.
Conservation of baculovirus inhibitor of apoptosis repeat proteins (birps) in viruses nematodes vertebrates and yeasts.
Trends in Biochemical Sciences 1998 23(5):159-162

Uren AG. Vaux DL.
Viral inhibitors of apoptosis. (Review)
Vitamins & Hormones 1997 53:175-193

Hawkins CJ. Uren AG. Hacker G. Medcalf RL. Vaux DL.
Inhibition of interleukin 1-beta-converting enzyme-mediated apoptosis of mammalian cells by baculovirus IAP.
P.N.A.S. 1996 93(24):13786-13790

Uren AG. Vaux DL.
Molecular and clinical aspects of apoptosis. (Review)
Pharmacology & Therapuetics 1996 72(1):37-50

Uren AG. Vaux DL.
Traf proteins and meprins share a conserved domain.
Trends in Biochemical Sciences 1996 21(7):244-245

Uren AG. Pakusch M. Hawkins CJ. Puls KL. Vaux DL.
Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumour necrosis factor receptor-associated factors.
P.N.A.S. 1996 93(10):4974-4978