Professor Owen Patrick Smith
Medical School, Paediatrics
Regius Professor of Physic (1637), Molecular Medicine Ireland
Biography
My main area of ongoing research for the past number of years has been elucidating the relationship (at the molecular and cellular level) between the protein C (PC) activation pathway and the systemic inflammatory response sepsis syndromes. To date, the research group has made significant clinical and scientific contributions to the emergence of a new paradigm regarding the patho-biology of severe sepsis / septic shock and we believe that this work has been instrumental in establishing APC/PC replacement therapy in this catastrophic disease, as all other novel therapeutic interventions in these patients have failed. This work has been carried out wholly in Ireland and has been supported in part by the Health Research Board of Ireland and Children's Medical & Research Foundation. The research programme has generated numerous PhD, MD and MSc studentships and peer reviewed publications in the Lancet, Blood, Thrombosis and Haemostasis and the British Journal of Haematology.
Publications and Further Research Outputs
Peer-Reviewed Publications
Piccin Andrea, Murphy Ciaran, Eakins Elva, Kunde Jan, Corvetta Daisy, Di Pierro Angela, Negri Giovanni, Guido Mazzoleni, Sainati Laura, Mc Mahon Corrina, Circulating microparticles, protein C, free protein S and endothelial vascular markers in children with sickle cell anaemia , Journal of extracellular vesicles , 4 , 2015
Hicks, P., Grimson, J. Smith, O., With a little help from my friends: experiences of building a virtual community for children with cancer, The Journal of Community Informatics: Special Issue: Community Informatics for Improving Health, 9, (2), 2013, p1 - 15
Sargent J, O'Marcaigh A, Smith O.P., Butler K, Gavin G, O'Sullivan M, Candida albicans - associated necrotizing vasculitis producing life-threatening gastrointestinal hemorrhage., Human Pathology, 41, (4), 2010, p602-604
J Bruneau, A O'Marcaigh, O.P. Smith, Pro-inflammatory and pro-coagulant properties of 6-thioguanine and 6-mercaptopurine: implications for their potential role in the development of sinusoidal obstructive syndrome, Leukemia & Lymphoma, 51, (1), 2010, p164-167
Kelly K, Smith OP, Storey L, O'Sullivan M, McDermott M, Butler K, McMahon C, Corbally M, O'Marcaigh A, Esophageal stricture during treatment for acute lymphoblastic leukaemia, Journal of Pediatric Hematology/Oncology, 32, (2), 2010, p124-127
RT McGrath, E McRae, O.P. Smith, J.S. O'Donnell, Platelet Von Willebrand factor - structure, function and biological importance, 148, 2010, p824-843
Piccin A, Smith OP, Murphy C, O'Marcaigh A, Corbally M, Mc Mahon C., Splenectomy in sickle cell anaemia: a cause of further crises?, British Journal of Haematology, 145, (1), 2009, p144-146
Kaspers G, Gibson B, Grimwade D, Pession A, Smith OP, Testi AM. , Central nervous system involvement in relapsed acute promyelocytic leukemia., Pediatric Blood & Cancer, 53, (2), 2009, p235-236
Beel K, Cotter MM, Blatny J, Bond J, Lucas G, Green F, Vanduppen V, Leung DW, Rooney S, Smith OP, Rosen MK, Vandenberghe P., A large kindred with X-linked neutropenia with an I294T mutation of the Wiskott-Aldrich syndrome gene., British Journal of Haematology, 144, (1), 2009, p120-126
Haematological Problems in, editor(s)Puri P and Hallwarth M , Paediatric Surgery: Diagnosis and Management, Berlin Heidelberg, Springer-Verlag,, 2009, [OP Smith ]
Piccin A, O'Marcaigh A, Deiratany S, Mc Mahon C, Smith OP., Severe gastrointestinal haemorrhage, first manifestation of neonatal haemophilia A, Haemophilia, 15, (3), 2009, p817-819
Desmond R, McDerra J, Kelly K, Smith O., Multiple vertebral collapse as a presentation of childhood acute lymphoblastic leukaemia., British Journal of Haematology, 144, (5), 2009, p627-628
RJS Preston, JA Johnson, F Ni Ainle, S Harmon, J Johnston, , OP Smith, B White and JS O'Donnell, Platelet factor 4 mediates activated protein C resistance by impairment of protein S cofactor enhancement, Journal of Biological Chemistry, 284, (9), 2009, p5869-5875
Smith, O. P. , Thrombotic Disease in Children with Cancer, Vnitr Lek, 55, (3), 2009, p223-226
S Mc Cann, Robin Foa, O.P. Smith Eibhlin Conneally, Clinical Cases Uncovered Haematology , 2nd Edition, Wiley-Blackwell Publishing, 2009
Ryan J, Quinn F, Meunier A, Boublikova L, Crampe M, Tewari P, O'Marcaigh A, Stallings R, Neat M, O'Meara A, Breatnach F, McCann S, Browne P, Smith O, Lawler M., Minimal residual disease detection in childhood acute lymphoblastic leukaemia patients at multiple time-points reveals high levels of concordance between molecular and immunophenotypic approaches., British Journal of Haematology, 144, (1), 2009, p107-115
Haematology in, editor(s)Gardner M , Foundations in Paediatrics, Oxford, Oxford University Press, 2009, [OP Smith and J Bond]
Hochart H, Jenkins PV, Preston RJ, Smith OP, White B, O'Donnell J., Concentration-dependent roles for heparin in modifying lipopolysaccharide-induced activation of mononuclear cells in whole blood., Thrombosis and Haemostasis , 99, (3), 2008, p570-575
Kelly K, McMahon C, Langabeer S, Eliwan H, O'Marcaigh A, Smith OP., Congenital JAK2V617F polycythemia vera: where does the genotype-phenotype diversity end?, Blood, 112, (10), 2008, p4356-4357
S Harmon, RJS Preston, F Ni Ainle, J Johnston, MS Cunningham, OP Smith, B White and JS O'Donnell, Dissociation of activated protein C functions by elimination of protein S cofactor enhancement, Journal of Biological Chemistry, 283, (45), 2008, p30531-30539
Piccin, A., Russell, J.D., Fleming, P., Butler, K., McDermott, M., Smith, O.P., O'Marcaigh, A., Invasive rhino-maxillary mucormycosis diagnosed before HSCT, Pediatric Blood and Cancer , 50, (2), 2008, p393-395
Hochart, H, Jenkins, PV, Preston, RJ, Smith, OP, White, B, O'Donnell, J, Concentration-dependent roles for heparin in modifying lipopolysaccharide-induced activation of mononuclear cells in whole blood., Thrombosis and Haemostasis, 99, (3), 2008, p570 - 575
D Bercovich, I Ganmore, LM. Scott, G Weinreb, A Elimelech, C Shochat, G Cazzaniga, A Biondi, G Basso, G Cario, MSchrappe, M Stanulla, S Strehl, OA. Haas, GMann, VBinder, A Borkhardt, H Kempski, J Trka, B Bielorei, S Avigad, B Stark, OP Smith , N Dastugue, J-P Bourquin, NBen Tal, AR. Green, SIzraeli, Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down's syndrome , Lancet, 372, (9648), 2008, p1484-1492
Blatny J, Kohlerova S, Zapletal O, Fiamoli V, Penka M, Smith O., Prophylaxis with recombinant factor VIIa for the management of bleeding episodes during immune tolerance treatment in a boy with severe haemophilia A and high-response inhibitors., Haemophilia., 14, (5), 2008, p1140-1142
KC. Lo, J Chalker S Strehl, M Neat, OP Smith, N Dastugue, L Kearney, SIzraeli, H Kempski and JK Cowell, Array Comparative Genome Hybridization Analysis of Acute Lymphoblastic Leukemia and Acute Megakaryoblastic Leukemia in Patients with Down Syndrome, British Journal of Haematology, 142, (6851), 2008, p934-945
Jenkins PV, Egan H, Keenan C, O'Shea E, Smith OP, Nolan B, White B, O'Donnell J., Mutation analysis of haemophilia B in the Irish population: increased prevalence caused by founder effect., Haemophilia, 14, (4), 2008, p717-22
Piccin A, Fleming P, Eakins E, McGovern E, Smith OP, McMahon C., Sickle cell disease and dental treatment., Journal of Irish Dental Association, 54, (2), 2008, p75-79.
Haematological Disease in, editor(s) , Great Ormond Street Children's Hospital. Handbook for Paediatric Medicine and Surgery, Manson Publishing London, 2007, [O.P. Smith, I Hann]
Oshea J, Smith O, O'Marcaigh A, McMahon C, Geoghegan R, Cotter M., Breaking bad news--parents' experience of learning that their child has leukaemia., Irish Medical Journal, 100, (9), 2007, p588-590
O'Riordan JM, Fitzgerald J, Smith OP, Bonnar J, Gorman WA;, National Blood Users Group.Transfusion of blood components to infants under four months: review and guidelines., Irish Medical Journal, 100, (6), 2007
Bond, J., Shahdadpuri, R., Mc Mahon, C., O'Marcaigh, A., Cotter, M., Smith, O. , Successful treatment of acute Epstein-Barr virus infection associated with X-linked lymphoproliferative disorder with rituximab [1] , Pediatric Blood and Cancer, 49, (5), 2007, p761-762
Piccin A, Murphy WG, Smith OP. , Circulating microparticles: pathophysiology and clinical implications., Blood Reviews, 21, (3), 2007, p157-171
Boublikova L, Kalinova M, Ryan J, Quinn F, O'Marcaigh A, Smith O, Browne P, Stary J, McCann SR, Trka J, Lawler M., Wilms' tumor gene 1 (WT1) expression in childhood acute lymphoblastic leukemia: a wide range of WT1 expression levels, its impact on prognosis and minimal residual disease monitoring, Leukemia, 20, (2), 2006, p254 - 263
Eidenschenk C, Dunne J, Jouanguy E, Fourlinnie C, Gineau L, Bacq D, McMahon C, Smith O, Casanova JL, Abel L, Feighery C., A novel primary immunodeficiency with specific natural-killer cell deficiency maps to the centromeric region of chromosome 8, American Journal of Human Genetics, 78, (4), 2006, p721 - 727
Yeung J, Kempski H, Neat M, Bailey S, Smith O, Brady HJ., Characterization of the t(17;19) translocation by gene-specific fluorescent in situ hybridization-based cytogenetics and detection of the E2A-HLF fusion transcript and protein in patients' cells, Haematologica, 91, (3), 2006, p422 - 424
Lin F, Murphy R, White B, Kelly J, Feighery C, Doyle R, Pittock S, Moroney J, Smith O, Livingstone W, Keenan C, Jackson J., Circulating levels of beta2-glycoprotein I in thrombotic disorders and in, Lupus, 15, (2), 2006, p87 - 93
Hochart H, Vincent Jenkins P, Smith OP, White B, Low-molecular weight and unfractionated heparins induce a downregulation of inflammation: decreased levels of proinflammatory cytokines and nuclear factor-kappaB in LPS-stimulated human monocytes, Br J Haematol., 133, (1), 2006, p62 - 67
Donadel-Claeyssens, S., Aronis-Vournas, S., Auerswald, G., Van den Berg, M., Boeri, E., Chambost, H., Van Geet, C., (...), Smith, O., Thomas, A., Current co-ordinated activities of the PEDNET (European Paediatric Network for Haemophilia Management) , Haemophilia, 12, (2), 2006, p124-127
Percy MJ, Crowley LJ, Davis CA, McMullin MF, Savage G, Hughes J, McMahon C, Quinn RJ, Smith O, Barber MJ, Lappin TR., Recessive congenital methaemoglobinaemia: functional characterization of the novel D239G mutation in the NADH-binding lobe of cytochrome b5 reductase, British Journal of Haematology, 129, (6), 2005, p847 - 853
Cotter M, Connell T, Colhoun E, Smith OP, McMahon C, Carbonic anhydrase II deficiency: a rare autosomal recessive disorder of, Journal of Pediatric Hematology/Oncology, 27, (2), 2005, p115 - 117
Piccin A, O'Marcaigh A, Smith O, O'Riordan J, Crowley M, Vandenberg E,Gardiner N, McCann S., Outcome of bone marrow transplantation in acquired and inherited aplastic anaemia in the Republic of Ireland, Irish Journal of Medical Sciences , 174, (3), 2005, p13 - 19
Chambost, H., Ljung, R., Aronis-Vournas, S., Auerswald, G., van de Berg, H.M., Boeri, E., Donadel-Claeyssens, S., (...), Smith, O., Thomas, A., Changing pattern of care of boys with haemophilia in western European centres , Haemophilia., 11, (2), 2005, 92-99
Reilly, M., Salim, A., Lawlor, E., Smith, O., Temperley, I., Pawitan, Y., Modelling infectious disease transmission with complex exposure pattern and sparse outcome data , Statistics in Medicine , 23, (19), 2004, p3013-3032
Balding, J., Livingstone, W.J., Conroy, J., Mynett-Johnson, L., Weir, D.G., Mahmud, N., Smith, O.P., Inflammatory bowel disease: The role of inflammatory cytokine gene polymorphisms , Mediators of Inflammation, 13, (3), 2004, p181-187
Finucane, D., Fleming, P., Smith, O., Dentoalveolar trauma in a patient with chronic idiopathic thrombocytopenic purpura: A case report , Pediatric Dentistry, 26, (4), 2004, p352-354
Balding J, Livingstone WJ, Pittock SJ, Mynett-Johnson L, Ahern T, Hodgson A, Smith OP, The IL-6 G-174C polymorphism may be associated with ischaemic stroke inpatients without a history of hypertension, Irish Journal of Medical Science, 173, (4), 2004, p200 - 203
Ahmed, M., Sternberg, A., Hall, G., Thomas, A., Smith, O., O'Marcaigh, A., Wynn, R., (...), Smith, O.P., Vyas, P., Natural history of GATA1 mutations in Down syndrome , Blood, 103, (7), 2004, 2480-2489
Kirke, P.N., Mills, J.L., Molloy, A.M., Brody, L.C., O'Leary, V.B., Daly, L., Murray, S., (...), Smith, O., Scott, J.M., Impact of the MTHFR C677T polymorphism on risk of neural tube defects: Case-control study , British Medical Journal, 328, (7455), 2004, p1535-1536
Cotter, M., Gulmann, C., Jeffers, M., Smith, O.P., Increased bone marrow angiogenesis in children with severe chronic neutropenia treated with granulocyte colony-stimulating factor , Journal of Pediatric Hematology/Oncology, 26, (8), 2004, p504-506
Research Expertise
Description
- The cellular and molecular basis of the liver toxicities (sinusoidal occlusion syndrome / veno-occlusive disease) following mylotarg and thioguanine as anti-leukaemia therapy.
- The role of MRD detection in childhood acute leukaemia (lymphoblastic & myeloblastic).
- The role of E2A-HLF transcript (t17:19) in childhood acute lymphoblastic leukaemia
- The molecular basis of the aplastic presentation of childhood acute lymphoblastic leukaemia
- The molecular pathogenesis of infant & childhood leukaemia's, dyshaematopoiesis of Down syndrome, inherited bone marrow failure syndromes, Wiskott-Aldrich syndrome, Shwachman-Diamond syndrome, and Kostmann's disease.
- The role of microvessel density index as a marker of angiogeneic potential in childhood acute lymphoblastic leukaemia.
- WASP mutations as a molecular trigger for congenital neutropenia
- The potential therapeutic role of recombinant FVIIa in, (i) reducing allogeneic blood product exposure in surgical (cardiac) neonatal cases and (ii) prevention of intraventricular haemorrhage in premature neonates
- Haemophilia A & B mutation analysis with carrier testing and prenatal diagnosis
- Mutational analysis of other inherited coagulation protein deficiencies
- von Willebrand disease characterisation by functional testing and molecular strategies
- Thrombophilic genotypes (FV506, FII20210, TL-MTHFR, PAI-1 (4G), ACE) in VTE disease
- Thrombophilic genomic polymorphic profiles in recurrent foetal loss women, inflammatory bowel disease patients and in stroke patients (paediatric and adult)
- The role of unfractionated heparins as anti-inflammatory mediators
- The role of unfractionated heparins in haemorrhagic inflammatory bowel disease
- Heparin induced thrombocytopenia and the role played by platelet Fc-gamma-IIa / Fc-gamma-IIIa receptors
- The efficacy of low molecular weight heparins as thrombophylaxis in pregnancy
Recognition
Representations
Awards and Honours
Excellence in Health Management Award Irish Healthcare Awards
31st St Lukes Lecture Improving outcome in adolescent cancer: avoiding throwing the baby out with the bathwater Royal Academy of Medicine in Ireland / St Lukes Hospital
Best Paper published in the Irish Journal of Medical Science The IL-6 G-174C polymorphism may be associated with ischaemic stroke in patients without a history of hypertension. IJMS Doctor Awards
41st Graves Lecture, Altering outcome in septic shock using a novel therapeutic approach Royal Academy of Medicine in Ireland / Health Research Board
National Outstanding Young Person of the Year in the area of Scientific Development Novel therapeutic intervention in severe meningococcaemia Junior Chamber Ireland
Sir John Banks Medal in Medicine Polyethyleneglycol modified cytokines: altering biological function Trinity College Dublin
Sheppard Memorial Prize in Medicine Polyethyleneglycol modified cytokines: altering biological function Trinity College Dublin
Postgraduate Travelling Scholarship in Medicine Polyethyleneglycol modified cytokines: altering biological function Trinity College Dublin
Honours in Surgical Finals
Dublin University Biological Association Presidents Prize (First place in Clinical Medicine)
Dublin University Biological Association Bronze Medal (First place in Undergraduate Research Projects)
Dublin University Biological Association Presidents Prize (First place in Clinical Medicine)
Overall honours in Pre-Clinical years
Memberships
Royal College of Pathologists, London , UK
Royal College of Physicians of Ireland
Royal College of Paediatricians and Child Health, London, UK
Royal College of Physicians of Edinburgh, UK
Royal College of Physicians of Glasgow, UK
Royal College of Physicians of London, UK
Royal Academy of Medicine in Ireland
Faculty of Pathology (Royal College of Physicians of Ireland)
Faculty of Paediatrics (Royal College of Physicians of Ireland)
American Society of Haematology, USA
British Society for Haematology, UK
Paediatric Haematology Forum of the British Society for Haematology, UK
European Paediatric Network for Haemophilia Management
United Kingdom Haemophilia Centre Directors Organisation, UK
Medical Research Council Childhood Leukaemia Working Party, UK
United Kingdom Children's Cancer Study Group, UK
Trinity College Medical Alumni Association of Dublin
The Worshipful Society of Apothecaries of London, UK