School of Medicine

Research Interests

IRG I3 

Our group studies the cell biology and biochemistry of eicosanoid generating enzymes, lipoxygenase and cyclooxygenase. A major focus is the use of lipidomic tools for characterising novel lipids generated by immune cells. One group of four lipids (15-HETE-PEs) were identified in ionophore activated human monocytes and murine macrophages (Maskrey et al, J Biol Chem, 2007, Morgan et al, J Biol Chem, 2009), and since then we have observed similar families in fMLP-activated neutrophils and thrombin-stimulated platelets (unpublished). We are now synthesising these lipids and determining their function in regulation of platelet and leukocyte function. One family (HETE-PEs) appear to be anti-inflammatory, through antagonising LPS induction of multiple cytokines (Morgan et al, J Biol Chem, 2009).

The laboratory is equipped with an Applied Biosystems 4000 Q-Trap, capable of high sensitivity quantitation, and structural analysis (funded by the Wellcome Trust). The instrument is focused solely on lipid analysis. We run an assay for various eicosanoids, including PGE2, PGD2, TXB2, LTB4, LXA4 and HETEs, HODES, etc, that is available to outside users on a collaborative basis.

Education & Qualifications

(1) 1990 - 1993:                                             
Ph.D. (Biochemistry),
Prof. OTG Jones, University of Bristol, U.K. & Dr. PJ England, SmithKline Beecham Pharmaceuticals, “Mechanism of iodonium compound inhibition of flavoenzymes”

(2) 1985 - 1989:                                             
Human Nutrition & Dietetics (B.Sc.), Hons. 2.1
University of Dublin, Trinity College, Ireland.
B.Sc. Thesis “Role of carotenoids in colorectal cancer”

Research Interests

Identification and characterisation of new lipids generated by activated immune cells in vitro and in vivo (Maskrey et al, J Biol Chem, 2007, and several papers in preparation). In July 2005, we established a mass spectrometry facility specifically for study of oxidised lipid mediators in inflammation (Applied Biosystems 4000 Q-Trap, Wellcome Trust Equipment Grant/SRIF2). We focussed on application of lipidomic techniques to the identification of esterified eicosanoids in activated human cells, and recently reported the structural characterisation of novel lipids generated by the 12/15-lipoxygenase pathway in monocytes, termed PE-HETEs.

Studies on interactions of nitric oxide with non-steroidal anti-inflammatory drugs and cyclooxygenase (Anning et al, Blood 2006, Williams et al, Blood, 2005, Clark et al, Biochem J 2005, O’ Donnell et al, J Biol Chem 2000).  In these studies we characterised the mechanisms by which the nitric oxide (NO) and cyclooxygenase (COX) pathways interact leading to modulation of vascular function and inflammation, in vitro and in vivo. These included demonstrating NO as a COX substrate and showing aspirin regulation of NO bioactivity in vivo.  Mechanisms which predispose to side-effects of non-steroidal anti-inflammatory drugs were revealed. It is suggested that monitoring NO bioactivity may identify patients at elevated risk of vascular side-effects of these drugs.

Lipoxygenase regulation of nitric oxide bioactivity in vitro and in vivo. (O’Donnell et al, J Biol Chem 1999, Coffey et al, Proc Natl Acad Sci USA, 2001, Anning et al, Am J Pathol 2005).  Lipoxygenase (LOX) is a lipid peroxidising enzyme implicated in hypertension and vascular disease. We established the enzymatic mechanisms by which the enzyme catalytically consumes NO and then showed that this reaction could regulate NO responses both in vitro and in vivo. Mice deficient in 12/15-LOX were protected against hypertension, partially due to elevated vascular eNOS expression and activity. The studies identify a pathway that antagonises NO signalling in vivo and may participate in hypertension through preventing the vasorelaxant effects of NO.

Selected Recent Publications

1. Morgan, AH, Dioszeghy, V., Maskrey, BH, Thomas, CP, Clark, SR, Mathie, SA, Lloyd, CM, Kuhn, H., Topley, N., Coles, B., Taylor, PR, Jones, SA. & O¹Donnell, VB ³Phosphatidylethanolamine-esterified eicosanoids in the mouse: tissue localisation and inflammation-dependent formation in Th-2 disease² (2009) J Biol Chem (in press) 

2. Gregory, L., Causton, B, Murdoch, J.R., Mathie, S.A., O¹Donnell, V.B., Thomas, C.P., Priest, F.M., Quint, D.J & Lloyd, C.M. (2009) ³Inhaled house dust mite induces pulmonary Th2 cytokine production.² Clin Exp Immunology (in press) 

3. Zhao, J., Maskrey, BH., Balzar, S., Chibana, K., Mustovich, A., Hu, H, Trudeau, JB, O¹Donnell V.B. and Wenzel, S.E. (2009) ³IL-13 induced MUC5AC is regulated by 15-lipoxygenase-1 pathway in huma bronchial epithelial cells² Am. J. Respir. & Crit. Care Medicine. 179(9):782-90 

4. Rubbo H, Trostchansky A, O'Donnell VB. ³Peroxynitrite-mediated lipid oxidation and nitration: mechanisms and consequences.² Arch Biochem Biophys. (2009) Apr 15;484(2):167-72 

5. Baker PR, Schopfer FJ, O'Donnell VB, Freeman BA. Convergence of nitric oxide and lipid signaling: Anti-inflammatory nitro-fatty acids. Free Radic Biol Med. (2009) Apr 15;46(8):989-1003

Selected Projects

Project:Wellcome Trust Biomedical Resources Grant ³Generation of lipid standards for biological studies: oxidized phospholipids generated by activated immune cells²
VB O¹Donnell (PI), C McGuigan, N Porter, M Bagley, G Milne (Co-Is)
Value:£191,231,
Duration:Oct 2009-Sept 2012

Project:Wellcome Trust Project Grant ³Characterisation of phospholipid-esterified eicosanoids generated by lipoxygenases²
O¹Donnell (Principal Investigator) T Wess, M Hallett, C McGuigan (Co Investigators).
Value:£234,374
Duration:Oct 2009-Sept 2012 VB

Project:Wellcome Trust Project Grant ³Nitroarachidonate and Cholesteryl nitrolinoleate as Novel Anti-inflammatory Nitrated Lipids: Detection, Synthesis, Characterization and Biological Properties²
H Rubbo, VB O¹Donnell (Investigators)
Value:£201,696,
Duration:Apr 08-Mar 11.

Project: Welsh Assembly Government/Medical Research Council Health Partnership Award. ³EURICA: The Epidemiology of Urinary Tract Infection (UTI) in Children with Acute Illness in Primary Care²
Christopher Butler (Principal Investigator), VB O¹Donnell, A Edwards, K O¹Brien, K Hood, N Topley, R Howe, C Powell, J van der Voort (Co-Investigators).
Value: £139,897
Duration:Jan 08-Dec 10

Project:British Lung Foundation Research Fellowship ³Formation of neutrophil extracellular traps in the development of chronic lung disease of prematurity²
Stephen Clark (Fellow), VB O¹Donnell, S Kotecha (Supervisors)
Value:£119,688
Duration:Jan 2008-Dec 2009

Project:European Union Marie Curie Intraeuropean Fellowship ³Defining the mechanisms by which platelets regulate the neutrophil extracellular traps in sepsis²
Stephen Clark (Fellow), VB O¹Donnell (Sponsor)
Value: £168,256

Project: Wellcome Trust Project Grant ³Structural and biological characterisation of novel phosphatidylethanolamine lipids generated by 12/15-lipoxygenase in monocytes and macrophages²
VB O¹Donnell (Principal Investigator) Dr SA Jones and Prof N Topley Co-investigators.
Value:£186,129
Duration:Aug 2006-Jul 2009,

Project:Medical Research Council/I3 IRG studentship ³Structural and in vivo characterisation of novel lipids generated by murine macrophages²
VB O¹Donnell (Principal Investigator), Prof N Topley Co-supervisor
Value:£65,000 approx
Duration:Oct 2006-Sept 2009

Project:Medical Research Council Capacity Building Studentship ³Therapeutic potential of interleukin-6 blockade in hypertension and vascular dysfunction²
Dr SA Jones, Principal supervisor, VB O¹Donnell (co-supervisor)
Value:£65,000 approx