James O’Donnell

Professor of Vascular Biology and Director of the Irish Centre for Vascular Biology

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Professor O’Donnell received his medical degree from Trinity College Dublin in 1990. After internship and medical residency in Australia, he completed clinical haematology training in the Hammersmith and Royal Free Hospitals in London. In 1998, he obtained a Medical Research Council Training Fellowship, and was awarded his PhD by Imperial College London in 2001. He subsequently completed a Post-Doctoral Fellowship in the Hammermith Hospital, and was appointed as Senior Lecturer in Imperial College in 2004. He is a Fellow of both the Royal College of Physicians of Ireland, and the Royal College of Pathologists (UK). Following his return to Ireland in 2005, he became the first clinician scientist to receive the prestigious Science Foundation Ireland President of Ireland Young Investigator award. He is currently Professor of Vascular Biology in the Royal College of Surgeons in Ireland and Director of the recently established Irish Centre for Vascular Biology. The Haemostasis Research laboratory led by Prof. O’Donnell has been awarded more than £12 million in peer-reviewed grant funding since 2006. In addition to the National Children’s Research Centre (NCRC), his research programme has been funded by Science Fondation Ireland, the Health Research Board (HRB), the Irish Heart Foundation, the Wellcome Trust and the. Prof O’Donnell’s laboratory has focussed on basic research related to different aspects of vascular biology in relation to clinical bleeding and thrombosis. He has published more than 100 publications in high impact peer reviewed journals (including the New England Journal of Medicine, Blood, ATVB and J Biol Chem). On the basis of this research, he has also been invited to give numerous lectures at the most prestigious national and international haematology meetings, including the American Society of Hematology Annual Meeting, the Gordon Coference in Hemostasis and the Congress of the International Society for Thrombosis and Haemostasis.

James O’Donnell

Professor of Vascular Biology and Director of the Irish Centre for Vascular Biology

Contact

jamesodonnell@rcsi.ie

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Dr Emilija Jerman
Position: Post-doctoral fellow
emilijajerman@rcsi.ie

Role:
Emilija is a post-doctoral scientist who is conducting our research into the mechanisms underlying blood vessel occlusion in children with cerebral malaria.

Defining the molecular mechanisms through which von Willebrand factor modulates the pathogenesis of childhood cerebral malaria - the NCRC Malaria Research Consortium

The global morbidity and mortality caused by malaria infection are staggering. Between 300 million and 500 million cases of clinical malaria occur each year, resulting in more than 500,000 deaths. Unfortunately, the majority of these deaths (~80%) occur in African children under age five. Consequently, malaria constitutes one of the leading causes of death in young children worldwide. Indeed the United Nations estimates that malaria is responsible for the death of a child in sub-Saharan Africa every 30 seconds. Cerebral malaria (CM) is a life-threatening complication of malaria infection. Young children with CM typically present to hospital with severe headache and drowsiness. Unfortunately, as the malaria infection worsens, the children rapidly progress to develop confusion, decreased consciousness and unrousable coma. Although effective anti-malarial drugs have been developed, in up to 20% of children CM still proves fatal. Furthermore, 20% of the children who survive CM are left with long term complications including learning difficulties and memory impairment. In spite of the significant mortality and morbidity associated with CM, the effects if the malaria parasite in causing disease remain poorly understood. This lack of understanding has impeded the development of new and much needed treatment options for children who develop CM. To further investigate the biology underlying CM in children, we have established a Malaria Research Consortium. This Consortium includes collaborators in Dublin, the Liverpool School of Tropical Medicine, University of Sydney and Blantyre in Malawi. In previous studies, this Consortium has identified a novel role for a specific blood clotting protein called von Willebrand factor (VWF) in malaria. In the blood, this clotting protein is able to bind to red cells infected with malaria parasites. In this study, the Consortium will investigate further how VWF influences malaria progression. Ultimately, we hope that insights into how VWF is important in children with malaria infection may provide new treatment options for children with CM.

The list of publications below is automatically derived from MEDLINE/PubMed. As a result, there may be incorrect or missing publications.

Ward S, O'Sullivan JM, O'Donnell JS, 2019 Jul, von Willebrand factor sialylation-A critical regulator of biological function. J Thromb Haemost, DOI: 10.1111/jth.14471

O'Donnell JS, O'Sullivan JM, Preston RJS, 2019 Jul, Advances in understanding the molecular mechanisms that maintain normal haemostasis. Br J Haematol, DOI: 10.1111/bjh.15872

Preston RJS, O'Sullivan JM, O'Donnell JS, 2019 Jul, Advances in understanding the molecular mechanisms of venous thrombosis. Br J Haematol, DOI: 10.1111/bjh.15869

Aguila S, Lavin M, Dalton N, Patmore S, Chion A, Trahan GD, Jones KL, Keenan C, Brophy TM, O'Connell NM, Ryan K, Byrne M, Nolan M, Patel A, Preston RJS, James P, Di Paola J, O'Sullivan JM, O'Donnell JS, 2019 Apr 4, Increased galactose expression and enhanced clearance in patients with low von Willebrand factor. Blood, DOI: 10.1182/blood-2018-09-874636

Aguila S, O'Donnell JS, 2019 Mar, Novel therapies for hemophilia A - the role of the von Willebrand factor chaperone. J Thromb Haemost, DOI: 10.1111/jth.14353

Dunne E, Qi QM, Shaqfeh ES, O'Sullivan JM, Schoen I, Ricco AJ, O'Donnell JS, Kenny D, 2019 Mar 21, Blood group alters platelet binding kinetics to von Willebrand factor and consequently platelet function. Blood, DOI: 10.1182/blood-2018-06-855528

Lavin M, O'Donnell JS, 2019 Feb 21, How I treat low von Willebrand factor levels. Blood, DOI: 10.1182/blood-2018-10-844936

Doherty D, Singleton E, Byrne M, Ryan K, O'Connell NM, O'Donnell JS, Lavin M, 2019 Feb, Missed at first Glanz: Glanzmann thrombasthenia initially misdiagnosed as Von Willebrand Disease. Transfus Apher Sci, DOI: 10.1016/j.transci.2018.11.008

Fogarty H, Byrne M, O’Connell NM, Ryan K, White B, O’Donnell JS, Lavin M, 2018 May 10, Acquired Factor Xiii Deficiency: An Uncommon But Easily Missed Cause Of Severe Bleeding Ir Med J, DOI: 10.1016/j.transci.2018.11.008

O'Sullivan JM, Ward S, Lavin M, O'Donnell JS, 2018 Oct, von Willebrand factor clearance - biological mechanisms and clinical significance. Br J Haematol, DOI: 10.1111/bjh.15565

Lavin M, Aguila S, Dalton N, Nolan M, Byrne M, Ryan K, White B, O'Connell NM, O'Sullivan JM, Di Paola J, James PD, O'Donnell JS, 2018 Jul 24, Significant gynecological bleeding in women with low von Willebrand factor levels. Blood Adv, DOI: 10.1182/bloodadvances.2018017418

Maguire CM, Lavin M, Doyle M, Byrne M, Prina-Mello A, O'Donnell JS, Volkov Y, 2018 Apr, The anticoagulant properties of cadmium telluride quantum dots. J Interdiscip Nanomed, DOI: 10.1002/jin2.35

Fogarty H, Doyle MM, Campbell R, Keenan C, White B, Ryan K, O'Donnell JS, Slevin J, O'Keeffe D, O'Connell NM, Lavin M, 2019 Feb, Management of combined factor V and factor VIII deficiency in pregnancy. J Obstet Gynaecol, DOI: 10.1080/01443615.2018.1448766

Ward SE, O'Sullivan JM, Drakeford C, Aguila S, Jondle CN, Sharma J, Fallon PG, Brophy TM, Preston RJS, Smyth P, Sheils O, Chion A, O'Donnell JS, 2018 Feb 22, A novel role for the macrophage galactose-type lectin receptor in mediating von Willebrand factor clearance. Blood, DOI: 10.1182/blood-2017-06-787853

McDonnell CJ, Soule EE, Walsh PT, O'Donnell JS, Preston RJS, 2018 Mar, The Immunoregulatory Activities of Activated Protein C in Inflammatory Disease. Semin Thromb Hemost, DOI: 10.1055/s-0037-1608910

Lavin M, Ryan K, White B, Byrne M, O'Connell NM, O'Donnell JS, 2018 Jan, A role for intravenous immunoglobulin in the treatment of Acquired Von Willebrand Syndrome associated with IgM gammopathy. Haemophilia, DOI: 10.1111/hae.13374

O'Sullivan JM, Preston RJS, Robson T, O'Donnell JS, 2018 Mar, Emerging Roles for von Willebrand Factor in Cancer Cell Biology. Semin Thromb Hemost, DOI: 10.1055/s-0037-1607352

Fallon PG, Lavin M, O'Donnell JS, 2018 Jan, SIPPET: insights into factor VIII immunogenicity. J Thromb Haemost, DOI: 10.1111/jth.13886

Lavin M, Aguila S, Schneppenheim S, Dalton N, Jones KL, O'Sullivan JM, O'Connell NM, Ryan K, White B, Byrne M, Rafferty M, Doyle MM, Nolan M, Preston RJS, Budde U, James P, Di Paola J, O'Donnell JS, 2017 Nov 23, Novel insights into the clinical phenotype and pathophysiology underlying low VWF levels. Blood, DOI: 10.1182/blood-2017-05-786699

Drakeford C, O'Donnell JS, 2017 Sep, Targeting von Willebrand Factor-Mediated Inflammation. Arterioscler Thromb Vasc Biol, DOI: 10.1161/ATVBAHA.117.309817

Gleeson EM, McDonnell CJ, Soule EE, Willis Fox O, Rushe H, Rehill A, Smith OP, O'Donnell JS, Preston RJS, 2017 Nov, A novel protein C-factor VII chimera provides new insights into the structural requirements for cytoprotective protease-activated receptor 1 signaling. J Thromb Haemost, DOI: 10.1111/jth.13807

Tobin WO, Kinsella JA, Kavanagh GF, O'Donnell JS, McGrath RT, Tierney S, Egan B, Feeley TM, Coughlan T, Collins DR, O'Neill D, Murphy S, Lim SJ, Murphy RP, McCabe D, 2017 Apr 15, Profile of von Willebrand factor antigen and von Willebrand factor propeptide in an overall TIA and ischaemic stroke population and amongst subtypes. J Neurol Sci, DOI: 10.1016/j.jns.2017.02.045

Brophy TM, Ward SE, McGimsey TR, Schneppenheim S, Drakeford C, O'Sullivan JM, Chion A, Budde U, O'Donnell JS, 2017 May, Plasmin Cleaves Von Willebrand Factor at K1491-R1492 in the A1-A2 Linker Region in a Shear- and Glycan-Dependent Manner In Vitro. Arterioscler Thromb Vasc Biol, DOI: 10.1161/ATVBAHA.116.308524

Lavin M, O'Donnell JS, 2016 Dec 2, New treatment approaches to von Willebrand disease. Hematology Am Soc Hematol Educ Program, DOI: 10.1182/asheducation-2016.1.683

O'Sullivan JM, Aguila S, McRae E, Ward SE, Rawley O, Fallon PG, Brophy TM, Preston RJ, Brady L, Sheils O, Chion A, O'Donnell JS, 2016 Dec, N-linked glycan truncation causes enhanced clearance of plasma-derived von Willebrand factor. J Thromb Haemost, DOI: 10.1111/jth.13537

Chion A, O'Sullivan JM, Drakeford C, Bergsson G, Dalton N, Aguila S, Ward S, Fallon PG, Brophy TM, Preston RJ, Brady L, Sheils O, Laffan M, McKinnon TA, O'Donnell JS, 2016 Oct 13, N-linked glycans within the A2 domain of von Willebrand factor modulate macrophage-mediated clearance. Blood, DOI: 10.1182/blood-2016-04-709436

Lakshmanan RS, Efremov V, O'Donnell JS, Killard AJ, 2016 Sep, Measurement of the viscoelastic properties of blood plasma clot formation in response to tissue factor concentration-dependent activation. Anal Bioanal Chem, DOI: 10.1007/s00216-016-9689-3

O'Sullivan JM, Jenkins PV, Rawley O, Gegenbauer K, Chion A, Lavin M, Byrne B, O'Kennedy R, Preston RJ, Brophy TM, O'Donnell JS, 2016 May, Galectin-1 and Galectin-3 Constitute Novel-Binding Partners for Factor VIII. Arterioscler Thromb Vasc Biol, DOI: 10.1161/ATVBAHA.115.306915

Lavin M, Brophy TM, Rawley O, O'Sullivan JM, Hayden PJ, Browne PV, Ryan K, O'Connell N, O'Donnell JS, 2016 Jun, Lenalidomide as a novel treatment for refractory acquired von Willebrand syndrome associated with monoclonal gammopathy. J Thromb Haemost, DOI: 10.1111/jth.13317

O'Sullivan JM, Preston RJ, O'Regan N, O'Donnell JS, 2016 May 12, Emerging roles for hemostatic dysfunction in malaria pathogenesis. Blood, DOI: 10.1182/blood-2015-11-636464

O'Regan N, Moxon C, Gegenbauer K, O'Sullivan JM, Chion A, Smith OP, Preston RJ, Brophy TM, Craig AG, O'Donnell JS, 2016 Apr, Marked elevation in plasma osteoprotegerin constitutes an early and consistent feature of cerebral malaria. Thromb Haemost, DOI: 10.1160/TH15-10-0796

Quinn LM, Drakeford C, O'Donnell JS, Preston RJ, 2015 Aug, Engineering activated protein C to maximize therapeutic efficacy. Biochem Soc Trans, DOI: 10.1042/BST20140312

O'Regan N, Gegenbauer K, O'Sullivan JM, Maleki S, Brophy TM, Dalton N, Chion A, Fallon PG, Grau GE, Budde U, Smith OP, Craig AG, Preston RJ, O'Donnell JS, 2016 Mar 3, A novel role for von Willebrand factor in the pathogenesis of experimental cerebral malaria. Blood, DOI: 10.1182/blood-2015-07-654921

Lavin M, Jenkins PV, Keenan C, White B, Betts DR, O'Donnell JS, O'Connell NM, 2016 Jan, X-linked moyamoya syndrome associated with severe haemophilia A. Haemophilia, DOI: 10.1111/hae.12806

Lavin M, Jenkins PV, Healy ML, Byrne M, O'Connell NM, O'Donnell JS, 2015 Nov, Age-related factor IX correction in symptomatic female carriers with haemophilia B Leyden. Haemophilia, DOI: 10.1111/hae.12761

Lavin M, Kavanagh J, Beddy P, O'Connell NM, O'Donnell JS, 2016 Jan, Recurrent lower limb venous thrombosis associated with a congenitally absent infrarenal inferior vena cava. QJM, DOI: 10.1093/qjmed/hcv123

Gleeson EM, Dichiara MG, Salicio A, Quinn LM, Drakeford C, Russell SE, Walsh PT, Orbe J, Hermida J, Smith OP, O'Donnell JS, Montes R, Preston RJ, 2015 Aug 13, Activated protein C β-glycoform promotes enhanced noncanonical PAR1 proteolysis and superior resistance to ischemic injury. Blood, DOI: 10.1182/blood-2015-03-632877

Rawley O, O'Sullivan JM, Chion A, Keyes S, Lavin M, van Rooijen N, Brophy TM, Fallon P, Preston RJ, O'Donnell JS, 2015 May, von Willebrand factor arginine 1205 substitution results in accelerated macrophage-dependent clearance in vivo. J Thromb Haemost, DOI: 10.1111/jth.12875

Kinsella JA, Tobin WO, Kavanagh GF, O'Donnell JS, McGrath RT, Tierney S, Feeley TM, Egan B, O'Neill D, Collins DR, Coughlan T, Harbison JA, Doherty CP, Madhavan P, Moore DJ, O'Neill SM, Colgan MP, Saqqur M, Murphy RP, Moran N, Hamilton G, McCabe DJ, 2015 Apr, Increased thrombin generation potential in symptomatic versus asymptomatic moderate or severe carotid stenosis and relationship with cerebral microemboli. J Neurol Neurosurg Psychiatry, DOI: 10.1136/jnnp-2013-307556

Tobin WO, Kinsella JA, Kavanagh GF, O'Donnell JS, McGrath RT, Coughlan T, Collins DR, O'Neill D, Egan B, Tierney S, Feeley TM, Murphy RP, McCabe DJ, 2014 Jul, Longitudinal assessment of von Willebrand factor antigen and von Willebrand factor propeptide in response to alteration of antiplatelet therapy after TIA or ischaemic stroke. J Neurol, DOI: 10.1007/s00415-014-7362-3

Kinsella JA, Tobin WO, Kavanagh GF, O'Donnell JS, McGrath RT, Tierney S, Feeley TM, Egan B, O'Neill D, Collins RD, Coughlan T, Harbison JA, Doherty CP, Madhavan P, Moore DJ, O'Neill SM, Colgan MP, Saqqur M, Murphy RP, Moran N, Hamilton G, McCabe DJ, 2014 Jul, Increased endothelial activation in recently symptomatic versus asymptomatic carotid artery stenosis and in cerebral microembolic-signal-negative patient subgroups. Eur J Neurol, DOI: 10.1111/ene.12403

McGrath RT, van den Biggelaar M, Byrne B, O'Sullivan JM, Rawley O, O'Kennedy R, Voorberg J, Preston RJ, O'Donnell JS, 2013 Dec 12, Altered glycosylation of platelet-derived von Willebrand factor confers resistance to ADAMTS13 proteolysis. Blood, DOI: 10.1182/blood-2013-04-496851

Harris LF, Rainey P, Castro-López V, O'Donnell JS, Killard AJ, 2013 Sep 7, A microfluidic anti-Factor Xa assay device for point of care monitoring of anticoagulation therapy. Analyst, DOI: 10.1039/c3an00401e

Preston RJ, Rawley O, Gleeson EM, O'Donnell JS, 2013 May 9, Elucidating the role of carbohydrate determinants in regulating hemostasis: insights and opportunities. Blood, DOI: 10.1182/blood-2012-10-415000

Tilley DO, Arman M, Smolenski A, Cox D, O'Donnell JS, Douglas CW, Watson SP, Kerrigan SW, 2013 May, Glycoprotein Ibα and FcγRIIa play key roles in platelet activation by the colonizing bacterium, Streptococcus oralis. J Thromb Haemost, DOI: 10.1111/jth.12175

Tobin WO, Kinsella JA, Kavanagh GF, O'Donnell JS, McGrath RA, Collins DR, Coughlan T, O'Neill D, Egan B, Tierney S, Feeley TM, Murphy RP, McCabe DJ, 2013 Feb, Longitudinal assessment of thrombin generation potential in response to alteration of antiplatelet therapy after TIA or ischaemic stroke. J Neurol, DOI: 10.1007/s00415-012-6684-2

Jenkins PV, Rawley O, Smith OP, O'Donnell JS, 2012 Jun, Elevated factor VIII levels and risk of venous thrombosis. Br J Haematol, DOI: 10.1111/j.1365-2141.2012.09134.x

Jenkins PV, Keenan C, Keeney S, Cumming T, O'Donnell JS, 2012 May, Clinical utility gene card for: haemophilia B. Eur J Hum Genet, DOI: 10.1038/ejhg.2011.268

Castro-López V, Murray B, Harris LF, O'Donnell JS, Killard AJ, 2012 Jan, Effects of four commercially available factor Xa proteins on the fluorogenic anti-factor Xa assay when monitoring unfractionated heparin. Blood Coagul Fibrinolysis, DOI: 10.1097/MBC.0b013e32834ddf4d

Gleeson EM, O'Donnell JS, Preston RJ, 2012 Mar, The endothelial cell protein C receptor: cell surface conductor of cytoprotective coagulation factor signaling. Cell Mol Life Sci, DOI: 10.1007/s00018-011-0825-0

Harris LF, O'Brien A, Castro-López V, O'Donnell JS, Killard AJ, 2011 Dec, Comparison of the anticoagulant response of a novel fluorogenic anti-FXa assay with two commercial anti-FXa chromogenic assays. Thromb Res, DOI: 10.1016/j.thromres.2011.08.002

Castro-López V, Harris LF, O'Donnell JS, Killard AJ, 2011 Dec 15, Quantification of unfractionated heparin in human plasma and whole blood by means of novel fluorogenic anti-FXa assays. J Pharm Biomed Anal, DOI: 10.1016/j.jpba.2011.07.025

Harris LF, Castro-López V, Jenkins PV, O'Donnell JS, Killard AJ, 2011 Dec, Comparison of a fluorogenic anti-FXa assay with a central laboratory chromogenic anti-FXa assay for measuring LMWH activity in patient plasmas. Thromb Res, DOI: 10.1016/j.thromres.2011.07.011

Bacon CL, Singleton E, Brady B, White B, Nolan B, Gilmore RM, Ryan C, Keohane C, Jenkins PV, O'Donnell JS, 2011 May, Low risk of inhibitor formation in haemophilia A patients following en masse switch in treatment to a third generation full length plasma and albumin-free recombinant factor VIII product (ADVATE®). Haemophilia, DOI: 10.1111/j.1365-2516.2010.02430.x

Ní Ainle F, O'Donnell JS, Johnson JA, Brown L, Gleeson EM, Smith OP, Preston RJ, 2011 Jan 14, Activated protein C N-linked glycans modulate cytoprotective signaling function on endothelial cells. J Biol Chem, DOI: 10.1074/jbc.M110.159475

Castro-López V, Harris LF, O'Donnell JS, Killard AJ, 2011 Jan, Comparative study of Factor Xa fluorogenic substrates and their influence on the quantification of LMWHs. Anal Bioanal Chem, DOI: 10.1007/s00216-010-4314-3

Harris LF, Castro-López V, Hammadi N, O'Donnell JS, Killard AJ, 2010 Jun 15, Development of a fluorescent anti-factor Xa assay to monitor unfractionated and low molecular weight heparins. Talanta, DOI: 10.1016/j.talanta.2010.03.030

McLean S, Ryan K, O'Donnell JS, 2010 Jun, Primary thromboprophylaxis in the palliative care setting: a qualitative systematic review. Palliat Med, DOI: 10.1177/0269216310365735

Gilmore R, Harmon S, Gannon C, Byrne M, O'Donnell JS, Jenkins PV, 2010 Jul 1, Thrombin generation in haemophilia A patients with mutations causing factor VIII assay discrepancy. Haemophilia, DOI: 10.1111/j.1365-2516.2009.02190.x

Please visit PubMed for more information on James O’Donnell's publications

Name:	Prof Owen Smith
Department	Haematology
Institution:	Our Ladys Children's Hospital, Crumlin
Country:	Ireland

Name:	Prof Alister Craig
Department	Biological Sciences
Institution:	Liverpool School of Tropical Medicine
Country:	UK

Name:	Prof Matthew Cambpell
Department	Genetics
Institution:	Trinity College Dublin
Country:	Ireland