Professor Owen Smith

Professor Owen Smith

Medical School, Paediatrics

Regius Professor of Physic (1637)

http://people.tcd.ie/smithow

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

  • 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 , 2015Journal Article, 2015, TARA - Full Text
  • 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 - 93Journal Article, 2006, 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 - 727Journal 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 - 424Journal Article, 2006, URL
  • 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 - 67Journal 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 - 263Journal Article, 2006, DOI
  • 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 - 203Journal Article, 2004
  • 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 - 19Journal Article, 2005
  • 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 - 853Journal 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 - 117Journal Article, 2005, 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 - 575Journal Article, 2008, 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, p817-819Journal Article, 2009, DOI
  • Smith, O. P. , Thrombotic Disease in Children with Cancer, Vnitr Lek, 55, (3), 2009, p223-226Journal Article, 2009
  • 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, p5869-5875Journal Article, 2009, 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, p144-146Journal Article, 2009, DOI
  • 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, p107-115Journal 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, p120-126Journal Article, 2009, DOI
  • 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, p627-628Journal Article, 2009, 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, p4356-4357Journal 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, p1484-1492Journal Article, 2008, DOI , URL
  • 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, p30531-30539Journal 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, p934-945Journal 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
  • 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, p1140-1142Journal 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, p717-22Journal 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, p570-575Journal Article, 2008, DOI
  • 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, p588-590Journal Article, 2007
  • 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, p393-395Journal Article, 2008, DOI
  • 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), 2007Journal Article, 2007
  • Piccin A, Murphy WG, Smith OP. , Circulating microparticles: pathophysiology and clinical implications., Blood Reviews, 21, (3), 2007, p157-171Journal Article, 2007, DOI
  • 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, p761-762Journal Article, 2007, 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, p124-127Journal Article, 2006, DOI
  • 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, 92-99Journal 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, p3013-3032Journal 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, p504-506Journal 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, p352-354Journal Article, 2004
  • 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, p1535-1536Journal 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, p181-187Journal Article, 2004, DOI
  • 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, 2480-2489Journal Article, 2004, DOI
  • S Mc Cann, Robin Foa, O.P. Smith Eibhlin Conneally, Clinical Cases Uncovered Haematology , 2nd Edition, Wiley-Blackwell Publishing, 2009Book, 2009
  • Haematology in, editor(s)Gardner M , Foundations in Paediatrics, Oxford, Oxford University Press, 2009, [OP Smith and J Bond]Book Chapter, 2009
  • 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
  • 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
  • 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, p602-604Journal 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, p124-127Journal 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, p164-167Journal 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, p824-843Journal Article, 2010, 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, p235-236Journal Article, 2009, DOI
  • 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 - 15Journal Article, 2013, URL , TARA - Full Text

Research Expertise

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

  • 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
  • 41st Graves Lecture, Altering outcome in septic shock using a novel therapeutic approach Royal Academy of Medicine in Ireland / Health Research Board 2001
  • Sheppard Memorial Prize in Medicine Polyethyleneglycol modified cytokines: altering biological function Trinity College Dublin 1991
  • 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
  • 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
  • National Outstanding Young Person of the Year in the area of Scientific Development Novel therapeutic intervention in severe meningococcaemia Junior Chamber Ireland 1998
  • Excellence in Health Management Award Irish Healthcare Awards 2008, Dublin
  • Postgraduate Travelling Scholarship in Medicine Polyethyleneglycol modified cytokines: altering biological function Trinity College Dublin 1991
  • Sir John Banks Medal in Medicine Polyethyleneglycol modified cytokines: altering biological function Trinity College Dublin 1991
  • Dublin University Biological Association Presidents Prize (First place in Clinical Medicine) 12984
  • Overall honours in Pre-Clinical years 1982
  • Honours in Surgical Finals 1985
  • Faculty of Paediatrics (Royal College of Physicians of Ireland)
  • European Paediatric Network for Haemophilia Management
  • Trinity College Medical Alumni Association of Dublin
  • United Kingdom Haemophilia Centre Directors Organisation, UK
  • The Worshipful Society of Apothecaries of London, UK
  • American Society of Haematology, USA
  • Royal College of Pathologists, London , UK
  • Royal College of Physicians of Edinburgh, UK
  • Royal College of Paediatricians and Child Health, London, UK
  • Royal Academy of Medicine in Ireland
  • Faculty of Pathology (Royal College of Physicians of Ireland)
  • Royal College of Physicians of London, UK
  • Medical Research Council Childhood Leukaemia Working Party, UK
  • United Kingdom Children's Cancer Study Group, UK
  • Royal College of Physicians of Ireland
  • Paediatric Haematology Forum of the British Society for Haematology, UK
  • British Society for Haematology, UK
  • Royal College of Physicians of Glasgow, UK
  • 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
  • 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
  • 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
  • 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