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Valerie O'Donnell  PhD FMedSci MAE FLSW

Professor Valerie O'Donnell

PhD FMedSci MAE FLSW

Professor of lipid biochemistry, Division of Infection and Immunity

School of Medicine

Users
Available for postgraduate supervision

Overview

Our research uses mass spectrometry to discover and characterise new lipids (fats) made by circulating vascular cells that regulate immune defence and blood clotting.

Last year we showed how mitochondria support removal of bioactive lipids during inflammation (https://www.nature.com/articles/s41467-021-27766-8). We also characterised the lipid composition of SARS-CoV2, including revealing a high proportion of aminophospholipids on the surface.  These lipids are both pro-coagulant and can aid viral entry, raising questions about their role in COVID (https://www.jlr.org/article/S0022-2275(22)00041-4/fulltext).

Previously, we showed that human blood platelets generate a large number of oxidized phospholipids several of which help clotting factors in plasma work more effectively.  We also uncovered a new role for phospholipases in providing energy to the cell and how lipids in different people respond individually to aspirin (http://www.cardiff.ac.uk/news/view/264589-understanding-the-bodys-response-to-aspirin)

Our current research is focused on understanding the role of new lipids in vascular inflammation including abdominal aortic aneurysm, cardiovascular disease, dementia and wound healing. 

In 2016, the Wellcome Trust funded a £1.3M 5 yr initiative led by our group jointly with Babraham Institute, Cambridge, and University of California San Diego to fund continuation and further development of LIPID MAPS, the global online database and resource for lipid research (http://www.cardiff.ac.uk/news/view/380752-new-funding-boosts-lipidomics-research).

Our group is funded by grants from the Wellcome Trust (LIPID MAPS), British Heart Foundation Programme Grant, and we are part of the Medical Research Council-funded MAP/UK Network.

Publication

2024

2023

2022

2021

2020

2019

2018

2017

2016

2015

2014

2013

2012

2011

2010

2009

2008

2007

2006

2005

2004

2002

2001

Articles

Websites

Research

 

Metrics

Google Scholar H-index 63. Citations 3,273 in 2022, total 25.5K citations

Publications returned in RAE2002, RAE2008 and REF2014 with 7 externally reviewed at 3-4* in REF2014, lead or co-author on 9 publications returned in REF2021. 

 

Recent research from our laboratory

Recent studies have focused on understanding how mitochondrial removal of oxylipins is controlled during inflammation.  We identified genes which are upregulated to provide increased metabolism via b-oxidation following in vivo or in vitro induction of inflammation and revealed a new role for the enzyme carnitine palmitoyl transferase 1 (CPT1) in this process (Misheva et al).  Funded by BBSRC, we provided the first characterisation of the lipid composition of SARS-CoV2, revealing a phospholipid rich membrane that's high in cholesterol and with about 50% of the PE and PS externalised on the outer surface (Saud et al).  This work has implications for our understanding of how the virus interacts with host cells to transmit infection.  With Maria Fedorova and colleagues, we published a tool guide for lipidomics on LIPID MAPS (Ni et al), and contributed to the setting of international guidelines for Lipidomics via a guideline paper (McDonald et al).  Mass spectrometry revealed many new ceramides present in skin that were altered in psoriasis (Tyrrell et al). 

  1. Ni, Z, Wölk, M, Jukes,G, Mendivelso Espinosa,K, Ahrends,R, Aimo,L, Alvarez-Jarreta,J, Andrews,S, Bridge,A, Clair,GC, Conroy, MJ, Kopczyinki,D, Korf,A, Lopez-Clavijo,AF, Malik,A, Miranda Ackerman,J, Molenaar,MR, O’Donovan,C, Pluskal,T, Shevchenko,A Slenter,D, Siuzdak,G, Kutmon,M, Tsugawa,H, Willighagen,EL, Xia,J, O’Donnell, VB and Fedorova, M. (2023) Guiding the choice of informatics software and tools for lipidomics biomedical research applications. Nature Methods https://doi.org/10.1038/s41592-022-01710-0, 20 (2), 193-204
  2. McDonald, JG, Ejsing, CS, Kopczynski, D, Holčapek, M, Aoki, J, Arita, M, Arita, M, Baker, ES, Bertrand-Michel, J, Bowden, JA, Brügger, B, Ellis, SR, Fedorova, M, Griffiths, WG, Han, X, Hartler, J, Hoffmann, N, Koelmel, JP, Köfeler, HC, Mitchell, TW, O’Donnell, VB, Saigusa, D, Schwudke, D, Shevchenko, A, Ulmer, CZ, Wenk, MR, Witting, M, Wolrab, D, Xia, Y, Ahrends, R, Liebisch G, and Ekroos, K. (2022) Introducing the Lipidomics Minimal Reporting Checklist. Nature Metabolism (comment). https://doi.org/10.1038/s42255-022-00628-3
  3. Saud, Z, Tyrrell, VJ Protty, M, Statkute, E, Rubina, A, Bentley, K, White, D, Rodrigues, PDS, Murphy, RC, Köfeler, H, Griffiths, WJ, Alvarez-Jarreta, J,  Newcombe, RG, Heyman, J, Pritchard, M, McLeod, RWJ, Arya, A, Lynch, CA, Owens, D, Buurma, NJ, O’Donnell, VB, Thomas, DW, Stanton, RJ. The SARS-CoV2 envelope exposes high levels of pro-coagulant lipids and can be inactivated by surfactant-containing oral rinses in COVID19 (2022) J Lipid Res (J Lipid Res 2022 Apr 15;100208. doi: 10.1016/j.jlr.2022.100208)
  4. Misheva, M, Kotzamanis, K, Davies, L, Tyrrell, VJ, Rodrigues, PRRS, Benavides, GA, Hinz, C, Murphy, RC, Kennedy, P, Taylor, PR, Rosas, M, Jones, SA, Deshpande, S, Andrews, R, Czubala, MA, Gurney, M, Aldrovandi, M, Meckelmann, SW, Ghazal, P, Darley-Usmar, VM, White, D, O’Donnell, VB (2022) Oxylipin metabolism is controlled by mitochondrial b-oxidation during bacterial inflammation. Nat Commun 13, 139 (2022). 
  5. Tyrrell, VJ, Ali, F, Boeglin, WE, Andrews, R, Burston, J, Birchall, JC, Ingram, J, Murphy, RC, Piguet V, Brash AR, O’Donnell VB, Thomas CP. (2021) Lipidomic and transcriptional analysis of the Linoleoyl-omega-Hydroxyceramide biosynthetic pathway in human psoriatic lesions J Lipid Res (Jun 22;100094. doi: 10.1016/j.jlr.2021.100094)

2017-2020

In the last three years, we demonstrated that eoxPL play a regulatory role in the development of abdominal aortic aneurysm and that they can restore haemostatic defects in conditions of coagulation factor deficiency. We also showed altered lysophospholipid metabolism in a common inherited form of cardiovascular disease.  Through collaborations, we supported many external studies on the roles of bioactive lipids in inflammatory disease.  Software generated in our lab funded by ERC has been incorporated into the LIPID MAPS suite of tools for lipidomics data analysis.  Our BHF Programme grant was renewed in 2020.  Studies examining how lipids could be targeted for viral inactivation in COVID19 were been initiated in vitro and in vivo in collaboration with colleagues in the Systems Immunity Research Institute. With LIPID MAPS colleagues we have developed new guidelines for journal publications and lipid naming conventions.

  1. O’Donnell, VB, FitzGerald, GA, Murphy, RC, Liebisch, G, Dennis, EA, Quehenberger, O, Subramaniam, S, Wakelam, MJO (2020) Steps towards minimal reporting standards for lipidomics mass spectrometry in biomedical research publications Circulation: Genomics and Precision Medicine (in press)
  2. Alvarez-Jarreta, J, Fahy, E, O’Connor, A, Price, A, Benton, P, Siuzdak, G, Rodrigues, PRS, Hawksworth, JA, Valdivia-Garcia, M, Allen, SM, O’Donnell, VB (2020) LipidFinder 2.0: advanced informatics pipeline for lipidomics discovery applications Bioinformatics (in press), also on BioRxiv: https://doi.org/10.1101/2020.08.16.250878
  3. Ipsiez, N, Pickering, RJ, Rosas, M, Tyrrell, VJ, Davies, LC, Orr, SJ, Czubala, MA, Fathalla, D, Robertson, AAB, Bryant, CE, O’Donnell, VB, Taylor, PR (2020) Tissue resident macrophages actively suppress IL-1beta release via a reactive prostanoid/IL-10 pathway. EMBO J (2020)39:e103454
  4. Meckelmann, SW, Hawksworth, JI, White, D, Andrews, R, Rodrigues, P, O’Connor, A, Alvarez-Jarreta, J, Tyrrell, VJ, Hinz, C, Zhou, Y, Williams, J, Aldrovandi, M, Watkins, WJ, Engler, AJ, Lo Sardo, V, Slatter, DA, Allen, SM, Acharya, J, Mitchell, J, Cooper, J, Aoki, J, Kano, K, Humphries, SE, and O’Donnell, VB. (2020) Metabolic dysregulation of the lysophospholipid/autotaxin axis in the chromosome 9p21 gene SNP rs10757274 Circulation: Genomics and Precision Medicine (https://doi.org/10.1161/CIRCGEN.119.002806)
  5. O’Donnell, VB, Thomas, D, Stanton, R, Maillard, JY, Murphy, RC, Jones, SA, Humphreys, I, Wakelam, MJO, Fegan, C, Wise, MP, Bosch, A, Stattar, SA Potential role of oral rinses targeting the viral lipid envelope in SARS-CoV-2 infection. (2020) FUNCTION. https://doi.org/10.1093/function/zqaa002
  6. Doll, S, Freitas, FP, Shah, R, Costa da Silva, M, Ingold, I, Grocin, AG, Panzilius, E, Scheel, C, Mourao, A, Buday, K, Wanninger, J, Vignane, T, Mohana, V, Rehberg, M, Schepers, A, O’Donnell, VB, Aldrovandi, M, Kurz, A, Sauer, M, Sattler, M, Tate, EW, Proneth, B, Schmitz, W, Schulze, A, Popowicz, G, Pratt, D, Friedmann Angeli, JP, Conrad, M (2019) FSP1 is a glutathione-independent ferroptosis inhibitor Nature doi:10.1038/s41586-019-1707-0
  7. Allen-Redpath, K, Aldrovandi, M, Lauder, S, Gketsopoulou, A. Tyrrell, VJ, Slatter, DA, Andrews, R, Watkins, WJ, Atkinson, G, McNeill, E, Gilfedder, A, Protty, M, Burston, J, Johnson, SRC, Rodrigues, PRS, Jones, DO, Lee, R, Handa, A, Channon, K, Obaji, S, Alvarez-Jarreta, J, Krönke, G, Ackermann, J, Jenkins, PV, Collins, PW and O’Donnell, VB. (2019) Phospholipid membranes drive abdominal aortic aneurysm development through stimulating coagulation factor activity. Proc Natl Acad Sci, USA 116 (16) 8038-8047 https://doi.org/10.1073/pnas.1814409116
  8. Slatter, DA, Percy, CL, Allen-Redpath, K, Gajsiewicz, J, Brooks, NJ, Clayton, A, Tyrrell, VJ, Lauder, SN, Watson, A, Dul, M, Garcia-Diaz, Y, Aldrovandi, M, Heurich, M, Hall, J, Morrissey, JH, Lacroix-Desmazes, S, Delignat, S, Jenkins, PV, Collins, PW and O’Donnell, VB (2018) Enzymatically-oxidized phospholipids restore blood clot formation in factor VIII deficiency through supporting factor activities on membrane surfaces J Clin Invest Insight 3(6):e98459. https://doi.org/10.1172/jci.insight.98459
  9. O’Donnell, VB, Rossjohn, J, Wakelam, MJO (2018) Phospholipid signalling in innate immune cells. J Clin Invest 128(7):2670-2679 https://doi.org/10.1172/JCI97944.

2007-2017

Since 2007, our group have discovered large numbers of lipids made by human platelets, neutrophils and monocytes, via the lipoxygenase and cyclooxygenase pathways. We have shown that these lipids can innate immunity including promoting blood clotting, immune signaling and antibacterial activities of leukocytes. They belong to families of enzymatically oxidized phospholipids (eoxPL), and their elevated generation is found in human thrombotic disease, while their deficiency leads to bleeding defects and protection against vascular inflammation. This work is done in collaboration with Prof Peter Collins and Dr Vince Jenkins (UHW).

  1. Lauder, SN, Allen-Redpath, K, Slatter, DA, Aldrovandi, M, O’Connor, A, Farewell, D, Percy, CL, Molhoek, JE, Rannikko, S, Tyrrell, VJ, Ferla, S, Milne, GL, Poole, AW, Thomas, CP, Obaji, S., Taylor, PR, Jones, SA, de Groot, PG, Urbanus, RT, Horkko S, Uderhardt, S, Ackermann, J, Jenkins, PV, Brancale, A, Kroenke, G, Collins, PW and O’Donnell, VB (2017) Networks of enzymatically oxidized membrane lipids support calcium - dependent coagulation factor binding to maintain hemostasis. Science Signaling Vol. 10, Issue 507, eaan2787, DOI: 10.1126/scisignal.aan2787
  2. O’Connor, A, Brasher, C, Slatter, DA, Meckelmann, SW, Hawksworth, JI, Allen, SM, O’Donnell, VB. (2017), LipidFinder, a computational workflow for discovery of lipids identifies new eicosanoid-phosphoinositides in platelets. J Clin Invest Insight 2(7):e91634. doi:10.1172/jci.insight.91634
  3. Slatter, DA, Aldrovandi, M, O’Connor, A, Allen, S, Brasher, C, Murphy, RC, Meckelmann, S, Ravi, S, Darley-Usmar, V and O’Donnell, VB. (2016) Mapping the human platelet lipidome reveals cytosolic phospholipase A2 as a regulator of mitochondrial bioenergetics during activation. Cell Metabolism 23, 930-934, with commentary by FitzGerald, GA, Human platelet lipidomics: variance, visualization, flux and fuel. 23, 757-759
  4. Hammond VJ, Morgan, AH, Thomas, CP, Brown, S, Freeman, BA, Lloyd, CM, Davies, J, Bush, A, Levonen, AL, Kansanen, E, Villacorta, L, Chen, YE, Porter, N, Garcia Diaz, YM, Schopfer, FJ & O’Donnell, VB (2012) Novel keto-phospholipids are generated by monocytes and macrophages, detected in cystic fibrosis and activate peroxisome proliferator-activated receptor-g. J Biol Chem 287, 41651–41666.
  5. O’Donnell, VB, Murphy, RC. New families of bioactive oxidized phospholipids generated by immune cells: identification and signaling actions. (2012) Blood 120, 1985-1992
  6. Clark, SR, Guy, CJ., Scurr, MJ, Thomas, CP, Coles, B., Roberts, G, Eberl, M., Jones, SA, Topley, N, Kotceha, S. and O’Donnell, VB (2011) Esterified eicosanoids are acutely generated by 5-lipoxygenase in primary human neutrophils and in human and murine infection” Blood 117, 2033-2043

1999-2007

On arriving in Cardiff, I defined with my colleagues how lipid oxidation mediated by vascular enzymes can control blood pressure both in vitro and in vivo. Main findings include showing how cellular lipoxygenases and cyclooxygenases catalytically consume nitric oxide resulting in vasoconstriction and how neutrophils patrol the vasculature maintaining blood pressure through dampening bacterial-induced inflammation.

  1. Morton, J., Coles, B., Wright, K., Gallimore, A., Morrow, JD, Terry, ES, Anning PB, Morgan, BP, Dioszeghy, V., Kuhn, H., Chaitidis, P, Hobbs, A., Jones, SA and O’Donnell, VB. (2008) “Circulating neutrophils maintain physiological blood pressure by suppressing bacteria and IFNg-dependent iNOS expression in the vasculature of healthy mice” Blood 111, 5187-94
  2. Anning, P.B, Coles, B., Wang, H., Morrow, J.D, Dey, S.K, Marnett, L.J. and O’Donnell, V.B. (2006) “Removal of nitric oxide is required for hypertensive and prothrombotic effects of COX-2 inhibition in vivo. Blood 108, 4059-4062
  3. Williams, P.C., Coffey, M.J., Coles, B., Sanchez, S., Morrow, J.D., Cockcroft, J.R., Lewis, M.J. and O’Donnell, V.B. “In vivo aspirin supplementation inhibits nitric oxide consumption by human platelets.” (2005) Blood 106, 2737-2743
  4. Coffey, M.J., Chumley, P.H., Coles, B., Natarajan, R., Thimmalapura, P., Nowell, M., Kühn, H., Lewis, M.J., Freeman, B.A. and O’Donnell, V.B. (2001) “Catalytic consumption of Nitric Oxide by 12/15-Lipoxygenase: Inhibition of Monocyte Soluble Guanylate Cyclase Activation.” Proc. Natl. Acad. Sci. USA 98, 8006-8011

1996-1999

While based at University of Alabama at Birmingham I worked with the Freeman lab to characterisedhow nitric oxide and lipid oxidation pathways intersect (published in JBC, Biochemistry), defining new biochemical routes to nitrolipid synthesis, and showing these lipids have potent anti-inflammatory actions.

  1. O’Donnell, V.B., Taylor, K.P., Parthasarathy, S., Kühn, H., Koesling, D., Friebe, A., Bloodsworth, A., Darley-Usmar, V.M. and Freeman, B.A. (1999) “15-Lipoxygenase catalytically consumes nitric oxide and impairs activation of guanylate cyclase” J. Biol. Chem 274, 20083-20091
  2. O’Donnell, V.B., Eiserich, J.P., Darley-Usmar, V.M., Chumley, P.H., Kirk, M., Barnes, S. and Freeman, B.A. (1999) Nitration of unsaturated lipid by nitric oxide derived reactive nitrogen species, peroxynitrite, nitrogen dioxide, nitrous acid and nitronium ion” Chem. Res. Toxicol. 12, 83-92
  3. Coles, B., Bloodsworth, A., Clark, S.R., Lewis, M.J., Cross, A.R., Freeman, B.A. and O’Donnell, V.B. (2002) “Nitrolinoleate inhibits multiple indices of neutrophil function” Circ. Res 91, 375-381 (Editorial, Freedman, J. “Nitrated lipids, defining their bioactivity” (2002) Circ. Res. 91, 371-372)
  4. Coles, B., Bloodsworth, A., Eiserich, J.P., Coffey, M.J., McLaughlin, R.M., Giddings, J.C., Lewis, M.J., Haslam, R.J., Freeman, B.A. and O’Donnell, V.B. (2002) “Nitrolinoleate inhibits platelet activation by attenuating calcium mobilization and inducing phosphorylation of vasodilator-stimulated phosphoprotein (VASP) through elevation of cAMP” J. Biol. Chem 277, 5832-5840

1990-1996

I studied at University of Berne, Switzerland on a Marie Curie Fellowship (1994-1996). I defined mechanisms of mitochondrial free radical generation. My PhD at University of Bristol (1990-1993) was focused on characterising the enzymatic action of iodonium compounds as flavoenzyme inhibitors that were in development as anti-inflammatory agents. I found that these are turnover dependent, irreversible inhibitors that form covalent adducts with flavin co-factors. These inhibitors represent some of the most widely used NADPH oxidase inhibitors still used today.

  1. O'Donnell, V.B., Smith, G.C.M. & Jones, O.T.G. (1994) "Involvement of phenyl radicals in iodonium compound inhibition of flavoenzymes". Molecular Pharmacology 46, 778-785
  2. O'Donnell, V.B., Tew, D.G., Jones, O.T.G., England, P.J. (1993) "Studies on the inhibitory mechanism of iodonium compounds with special reference to neutrophil NADPH oxidase." Biochem. J. 290, 1, 41-49.

 

Teaching

With my research group, I contribute to SSCs for our MBBCh programme, and UG projects for Medical Pharmacology (BSc) students.

I am module lead for the Immunomethodologies module in our MSc in Immunology .

I am an academic mentor for UG students in the MBBCh programme.

Biography

Education:

1993 PhD Bristol University, Biochemistry

1990 BSc, University of Dublin, Trinity College, Human Nutrition and Dietetics

Honours and awards

Honorary Officer of the Most Excellent Order of the British Empire (OBE) (2022-)

Biochemical Society Morton Lecture Award, 2022

Journal of Lipid Research Lectureship Award (2019)

Royal Society Wolfson Research Merit Awardee (2017)

ERC Advanced Investigator (2014-2019)

Marie Curie Excellence Award (EU), Brussels, March 2008

Wellcome Trust University Award, Cardiff University, 2002-2007

Iron Bolt Award, Gordon Research Conference on Oxygen Radicals, 2004

Wellcome Trust RCD Fellow, Cardiff University, 1999-2002

Parker B Francis Pulmonary Fellow, University of Alabama at Birmingham, 1997-1999

European Union Marie Curie Fellow, University of Berne, Switzerland, 1995-1996

Professional memberships

Member, Academia Europaea (2020-)

Associate Group Lead, Babraham Institute Cambridge (2020-2022)

Fellow of the Academy of Medical Sciences (2020-)

Fellow of the Learned Society of Wales, April 2015-

Associate Member, UK DRI, UK Dementia Research Insitute (Oct 2020-)

Honorary Professor, Faculty of Medicine, University of the Republic, Montevideo, since 2008.

Committees and reviewing

Recent only

-Member and Deputy Chair (since 2023), Multimorbidities Steering Group, Medical Research Council/NIHR (2018-)

-Steering Group, International Conference on Bioscience of Lipids (ICBL) (2022-)

-Strategic Oversight Group, UKBiobank (2022-)

-Member, Wellcome Trust Cell Biology, Development & Physiology Discovery Advisory Group (2022-2023)

-Executive Editorial Group, Function, American Physiological Society, 2020-.

-Member, MRC Capital Equipment Funding Panel, 2021-2023

-Member, Sectional Committee for Academy of Medical Sciences SC3) 2020-2023

-Management group member for UK, for EU COST Action Network, EpiLIPIDNET, co-applicant (O’Donnell)

Supervisions

Lipid biochemistry

Cardiovascular research

Immunology of lipids

Inflammation

Engagement

LIPID MAPS Database and Resource funded by Cardiff-led funding from Wellcome Trust

In 2016, the Wellcome Trust funded a £1.3M 5 yr initiative led by our group jointly with Babraham Institute, Cambridge, and University of California San Diego to fund continuation and further development of LIPID MAPS, the global online database and resource for lipid research (http://www.cardiff.ac.uk/news/view/380752-new-funding-boosts-lipidomics-research).