Short CV/Education and training

  • 1994 – 1997
    B.A. (Hons) Natural Sciences. Part II Zoology, Emmanuel College, Cambridge University, UK

  • 1997 – 2002
    PhD Biochemistry with Prof. Julian Downward and Prof. Gerard Evan, Imperial Cancer Research Fund, London, UK

Selected publications

  • c-Myc deregulation induces mRNA capping enzyme dependency (2016) Lombardi O, Varshney D, Phillips NM and Cowling VH (2016) Oncotarget 2016 2016 DOI: 10.18632/oncotarget.12701

  • Molecular basis of RNA guanine-7 methyltransferase (RNMT) activation by RAM (2016) Varshney D, Petit A, Juan Bueren-Calabuig J, Jansen C, Peggie M, Piskialov A and Cowling VH Nucleic Acids Research 2016 Jul 15. pii: gkw637. [Epub ahead of print] PMID:27422871

  • Grasso L, Suska O, Davidson L, Gonatopoulos-Pournatzis T, Williamson R, Wasmus L, Wiedlich S, Peggie M, Stavridis MP and Cowling VH (2016) mRNA cap methylation in pluripotency and differentiation Cell Reports 2016 Aug 2;16(5):1352-65. doi: 10.1016/j.celrep.2016.06.089. Epub 2016 Jul 21. PMID:27452456

  • Aregger M, Kaskar A, Fernandez-Sanchez ME, Simone Weidlich S and Cowling VH (2016) CDK1-cyclinB activates RNMT co-ordinating mRNA cap methylation with G1 phase transcription Molecular Cell 2016 Mar 3;61(5):734-46. doi: 10.1016/j.molcel.2016.02.008

  • Preston GC, Sinclair LV, Kaskar A, Hukelmann JL, Navarro MN, Ferrero I, MacDonald HR, Cowling VH and Cantrell DA (2015) Single Cell Tuning of Myc Expression by Antigen Receptor Signal Strength and Interleukin 2 in T Lymphocytes EMBO J. 2015 Jul 1. pii: e20149025

  • Cowling VH, Turner S and Cole MD (2014) Burkitt's lymphoma-associated c-Myc mutations converge on a dramatically altered target gene response and implicate ribosome biogenesis in oncogenesis Oncogene. 2014 Jul 3;33(27):3519-27. doi: 10.1038/onc.2013.338. Epub 2013 Sep 9.

  • Gonatopoulos-Pournatzis T, Dunn S, Bounds R, and Cowling VH (2011) RAM/Fam103a1 is required for mRNA cap methylation Molecular Cell 2011 Nov18;44(4):585-596

  • Fernandez-Sanchez ME, Gonatopoulos-Pournatzis T, Preston G, Lawlor MA, and Cowling VH (2009) S-Adenosyl Homocysteine Hydrolase (SAHH) is required for Myc-induced mRNA cap methylation, protein synthesis and cell proliferation Mol Cell Biol 2009, Dec;29(23):6182-91. Epub 2009 Oct 5.

  • Cole MD and Cowling VH (2009) Specific regulation of mRNA cap methylation by the c-Myc and E2F1 transcription factors Oncogene 2009 Mar 5;28(9):1169-75. Epub 2009 Jan 12.

  • Cowling VH and Cole MD (2007) The Myc Transactivation Domain Promotes Global Phosphorylation of the RNA pol II Carboxy-terminal Domain Independently of Direct DNA Binding Mol Cell Biol, 2007 March; 27(6) p2059-2073

Selected projects

  • We investigate how oncogenes influence gene expression, with the ultimate goal of developing new therapeutic approaches to target cancer cells.

  • Our current focus is the mRNA methyl cap, a modification of the 5- end of mRNA. The methyl cap is essential for gene expression, directing RNA processing and translation initiation. We made one of the first observations that methyl cap synthesis is regulated in the cell, by the oncogene c-Myc. We demonstrated that c-Myc-induced methyl cap formation is necessary for c-Myc to regulate gene expression and cell proliferation, and inhibition of methyl cap is synthetic lethal with deregulated c-Myc, indicating it as a potential therapeutic target in cancers (MCB 2009 29:6182-91).

  • Our current research programme investigates how the methyl cap is synthesised and regulated, and whether it has potential as a therapeutic target.

  • 1. What is the mechanism of mRNA cap synthesis?

    We are using biochemistry and mass spectrometry to identify the cellular proteins which synthesise the methyl cap. We recently identified an obligate activator of the human cap methyltransferase, which we are now characterising (Mol Cell 2011 44:585-596)

  • 2. How is mRNA cap synthesis regulated?

  • We are using mass spectrometry and biochemistry to identify post-translational modifications which regulate the methyl cap synthetic enzymes. We are using high throughput cellular screening technologies to identify pathways which target the methyl cap enzymes. We have recently identified signalling pathways which differentially regulate mRNA cap formation at different stages of the cell cycle.

    We are currently investigating mRNA cap regulation in embryonic stem cells and T cells.

  • 3. Can mRNA cap formation be targeted therapeutically?

  • We have found that specific subsets of breast cancer lines are sensitive to inhibition of the cap methyltransferase using siRNA. We are now screening for compounds which inhibit the cap methyltransferase in human cells, with the aim of providing a tool compound and inhibiting tumour cell growth and proliferation.

Membership in scientific bodies/juries

  • Editorial Advisory Panel for the Biochemical Journal

  • Editorial Board American Journal of Cancer Research

Additional qualifications

  • Post-doctoral research with Prof. Michael Cole, 2003 – 2007

  • Department of Pharmacology and Toxicology, Dartmouth College, NH, USA

  • Department of Molecular Biology, Princeton University, NJ, USA


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