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Professor Owen Patrick Smith
Medical School, Paediatrics
Medical School, 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 Journal Article, 2015 TARA - Full Text

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 Journal Article, 2013 TARA - Full Text URL

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 Journal Article, 2010 DOI

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 Journal Article, 2010 DOI

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 Journal Article, 2010 DOI

RT McGrath, E McRae, O.P. Smith, J.S. O'Donnell, Platelet Von Willebrand factor - structure, function and biological importance, 148, 2010, p824-843 Journal Article, 2010 DOI

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 Journal Article, 2009 DOI

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 Journal Article, 2009 DOI

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 Journal Article, 2009 DOI

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 Journal Article, 2009 DOI

Haematological Problems in, editor(s)Puri P and Hallwarth M , Paediatric Surgery: Diagnosis and Management, Berlin Heidelberg, Springer-Verlag,, 2009, [OP Smith ] Book Chapter, 2009

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 Journal Article, 2009 DOI

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 Journal Article, 2009 DOI

Smith, O. P. , Thrombotic Disease in Children with Cancer, Vnitr Lek, 55, (3), 2009, p223-226 Journal Article, 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 Journal Article, 2009 DOI

S Mc Cann, Robin Foa, O.P. Smith Eibhlin Conneally, Clinical Cases Uncovered Haematology , 2nd Edition, Wiley-Blackwell Publishing, 2009 Book, 2009

Haematology in, editor(s)Gardner M , Foundations in Paediatrics, Oxford, Oxford University Press, 2009, [OP Smith and J Bond] Book Chapter, 2009

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 Journal Article, 2008 DOI

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 Journal Article, 2008 DOI

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 Journal Article, 2008 DOI

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 Journal Article, 2008 DOI

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 Journal Article, 2008 DOI

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 Journal Article, 2008 URL DOI

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 Journal Article, 2008 DOI

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 Journal Article, 2008 DOI

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 Journal Article, 2008 DOI

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. Journal Article, 2008

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] Book Chapter, 2007

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 Journal Article, 2007

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 Journal Article, 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 Journal Article, 2007 DOI

Piccin A, Murphy WG, Smith OP. , Circulating microparticles: pathophysiology and clinical implications., Blood Reviews, 21, (3), 2007, p157-171 Journal Article, 2007 DOI

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 Journal Article, 2006 DOI

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 Journal Article, 2006 DOI

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 Journal Article, 2006 URL

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 Journal Article, 2006 DOI

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 Journal Article, 2006 DOI

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 Journal Article, 2006 DOI

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 Journal Article, 2005 DOI

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 Journal Article, 2005 DOI

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 Journal Article, 2005

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 Journal Article, 2005 DOI

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 Journal Article, 2004 DOI

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 Journal Article, 2004 DOI

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 Journal Article, 2004

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 Journal Article, 2004

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 Journal Article, 2004 DOI

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 Journal Article, 2004 DOI

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 Journal Article, 2004 DOI

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

  • Childhood Acute Lymphoblastic Leukaemia Collaborative Group
  • Clinical Trials Service Unit Oxford, UK
  • Irish Medicines Board, Dublin.
  • Advisory Committee for Human Medicines (ex Member)
  • Advisory Committee for Blood Products (ex Member)
  • Blood Transfusion Service Board, Dublin.
  • Natioanl Blood Users Group
  • Medical Advisory Committee (ex Member)
  • Baxter-Immuno Plc, Vienna, Austria.
  • Protein therapeutics Advisory Committee
  • National Children's Hospital, Dublin
  • Medical Advisory Committee (ex Member)
  • St. James's Hospital, Dublin. Medical Advisory Committee
  • Children's Medical and Research Foundation - OLCH
  • Scientific Advisory Committee
  • National Haemophilia Council Paediatric Representative

Awards and Honours

Excellence in Health Management Award Irish Healthcare Awards 2008, Dublin

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 2006

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 2005

41st Graves Lecture, Altering outcome in septic shock using a novel therapeutic approach Royal Academy of Medicine in Ireland / Health Research Board 2001

National Outstanding Young Person of the Year in the area of Scientific Development Novel therapeutic intervention in severe meningococcaemia Junior Chamber Ireland 1998

Sir John Banks Medal in Medicine Polyethyleneglycol modified cytokines: altering biological function Trinity College Dublin 1991

Sheppard Memorial Prize in Medicine Polyethyleneglycol modified cytokines: altering biological function Trinity College Dublin 1991

Postgraduate Travelling Scholarship in Medicine Polyethyleneglycol modified cytokines: altering biological function Trinity College Dublin 1991

Honours in Surgical Finals 1985

Dublin University Biological Association Presidents Prize (First place in Clinical Medicine) 1985

Dublin University Biological Association Bronze Medal (First place in Undergraduate Research Projects) 1984

Dublin University Biological Association Presidents Prize (First place in Clinical Medicine) 12984

Overall honours in Pre-Clinical years 1982

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