Roger Preston

Roger Preston

Lecturer in Vascular Biology

The Preston Lab is part of the Irish Centre for Vascular Biology and Department of Molecular and Cellular Therapeutics at Royal College of Surgeons in Ireland (RCSI), based at St Stephen’s Green, Dublin.

The research in our lab is focused on enhancing our understanding of coagulation factor biology and function, and using these insights to develop novel therapeutics for vascular dysfunction and inflammatory disease.

Roger Preston obtained his BSc. (Hons) in Molecular Biology from University of Aberdeen (2000), completed an MSc. in Bioengineering at the University of Strathclyde (2001), then attained his PhD at Imperial College London (2004). He has received several individual fellowship awards, including a Health Research Board Research Fellowship (2007), a Science Foundation Ireland Starting Investigator Research Grant (2009), and a Haematology Association of Ireland Scholar Award (2010). His research has been recognized by international research awards including the Novo Nordisk ‘Access-To-Insight’ Research Prize (2010), Bayer Hemophilia Award Program Early Career Investigator Award (2013), Daiichi-Sankyo Irish Heart Foundation Award (2015), and Bayer Hemophilia Special Project award (2016).

Dr Roger Preston and his research team (RCSI 2018)

He was appointed Assistant Professor in Immunology at Trinity College Dublin in 2012, then moved to the Royal College of Surgeons in Ireland in 2016. At RCSI, he is a Lecturer in Vascular Biology in the Department of Molecular and Cellular Therapeutics. He was formerly the Scientific Secretary of the Haematology Association of Ireland (2015-2017) and currently serves on the Editorial Board of Seminars in Thrombosis and Haemostasis (2015-present) and Research and Practice in Thrombosis and Haemostasis (2016-present). His research group is currently funded by awards from Science Foundation Ireland, Bayer Healthcare, and the National Children’s Research Centre.

Roger Preston

Lecturer in Vascular Biology

Orla Willis Fox
Position: PhD student

PhD student – SFI CDA

Hannah Rushe
Position: PhD student

PhD student

Aisling Rehill
Position: PhD student

PhD student – SFI iPATH Stratetgic Partnership Award

Erin Soule
Position: Postdoctoral scientist

Postdoctoral scientist – SFI CDA

Cormac McDonnell
Position: Postdoctoral scientist

Postdoctoral scientist – Bayer Haemophilia Award Programme

Sean McCluskey
Position: Postdoctoral scientist

NCRC supported postdoctoral researcher. Dr McCluskey is investigating the role of anticoagulant proteases in paediatric sickle cell disease.

Engineered recombinant activated protein C as a novel therapeutic agent for children with inflammatory bowel disease

The number of children with paediatric inflammatory bowel disease (PIBD) in Ireland has surged in the last 15 years. Current treatments for children with IBD are often ineffective so new approaches that expand the repertoire of efficacious treatments for PIBD are required. In this study, we will assess whether children with IBD attending OLCHC for treatment exhibit impaired anticoagulant and anti-inflamamtory pathway activity in their intestinal lining compared to healthy children. These studies will shed new light on the role of the PC pathway in regulating IBD development in children.

Novel therapeutic approach to counter vaso-occlusive crisis in sickle cell disease using engineered activated protein C

Sickle cell disease (SCD) is a significant cause of global paediatric illness and death. SCD causes red blood cells to bind to other blood cells and block blood vessels, which can cause painful sickle cell ‘crises’ and stroke to occur. There are only a limited number of therapies currently available to treat SCD. The objective of this study is to evaluate the role of activated protein C (APC), a blood protein with anticoagulant and anti-inflammatory activity, in controlling SCD, with a view to utilising engineered activated protein C variants as potential therapies for the treatment of SCD-associated blood vessel damage. This study will utilise the newly-established biobank of paediatric SCD blood samples collected as part of the Sickle Vascular Ireland Consortium (SiVIC) study to investigate the role of defective protein C pathway activity in SCD-associated vascular inflammation and occlusion. Specifically, we propose to determine whether the protein C pathway is impaired in individuals with SCD at different disease stages and treatment and investigate whether activated protein C has the potential to mitigate the key molecular events that contribute to SCD blood vessel dysfunction, such as inflammation, blood cell binding to sticky blood vessels and uncontrolled blood coagulation. SCD is a significant cause of global paediatric illness and death. Children with SCD are subject to painful crises, anaemia and stroke. Unfortunately, there is a limited understanding of the molecular events that lead to blood vessel occlusions that contribute to crises and therefore a limited number of effective SCD therapies. This study aims to test new therapeutic approaches to reduce the painful symptoms of SCD and meet the urgent, unmet need for novel therapies to enhance care of children with SCD.

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

Heestermans M, Naudin C, Mailer RK, Konrath S, Klaetschke K, Jämsä A, Frye M, Deppermann C, Pula G, Kuta P, Friese MA, Gelderblom M, Sickmann A, Preston RJS, Nofer JR, Rose-John S, Butler LM, Salomon O, Stavrou EX, Renné T, 2021 Sep 22, Identification of the factor XII contact activation site enables sensitive coagulation diagnostics. Nat Commun, DOI: 10.1038/s41467-021-25888-7
Fogarty H, Townsend L, Morrin H, Ahmad A, Comerford C, Karampini E, Englert H, Byrne M, Bergin C, O'Sullivan JM, Martin-Loeches I, Nadarajan P, Bannan C, Mallon PW, Curley GF, Preston RJS, Rehill AM, McGonagle D, Ni Cheallaigh C, Baker RI, Renné T, Ward SE, O'Donnell JS, Irish COVID-19 Vasculopathy Study (iCVS) investigators., 2021 Oct, Persistent endotheliopathy in the pathogenesis of long COVID syndrome. J Thromb Haemost, DOI: 10.1111/jth.15490
Giannoudaki E, Stefanska AM, Lawler H, Leon G, Hernandez Santana YE, Hassan N, Russell SE, Horan R, Sweeney C, Preston RS, Mantovani A, Garlanda C, Fallon PG, Walsh PT, 2021 Jul 12, SIGIRR Negatively Regulates IL-36-Driven Psoriasiform Inflammation and Neutrophil Infiltration in the Skin. J Immunol, DOI: 10.4049/jimmunol.2100237
Rehill AM, McCluskey S, O'Donnell JS, Dockal M, Preston RJS, iPATH Study Group., 2021 Mar, Heterogeneity in Bleeding Tendency and Arthropathy Development in Individuals with Hemophilia. Semin Thromb Hemost, DOI: 10.1055/s-0041-1723769
Preston RJS, O'Sullivan JM, 2021 Mar, Personalized Approaches to the Treatment of Hemostatic Disorders. Semin Thromb Hemost, DOI: 10.1055/s-0041-1723800
Rehill AM, Preston RJS, 2020 Sep, A new thrombomodulin-related coagulopathy. J Thromb Haemost, DOI: 10.1111/jth.14987
O'Sullivan JM, Gonagle DM, Ward SE, Preston RJS, O'Donnell JS, 2020 Aug, Endothelial cells orchestrate COVID-19 coagulopathy. Lancet Haematol, DOI: 10.1016/S2352-3026(20)30215-5
Gleeson EM, Rehill AM, Willis Fox O, Ni Ainle F, McDonnell CJ, Rushe HJ, McCluskey S, O'Donnell JS, Preston RJS, 2020 Jun 9, Apolipoprotein A-I enhances activated protein C cytoprotective activity. Blood Adv, DOI: 10.1182/bloodadvances.2019001316
Hughes MM, Hooftman A, Angiari S, Tummala P, Zaslona Z, Runtsch MC, McGettrick AF, Sutton CE, Diskin C, Rooke M, Takahashi S, Sundararaj S, Casarotto MG, Dahlstrom JE, Palsson-McDermott EM, Corr SC, Mills KHG, Preston RJS, Neamati N, Xie Y, Baell JB, Board PG, O'Neill LAJ, 2019 Oct 1, Glutathione Transferase Omega-1 Regulates NLRP3 Inflammasome Activation through NEK7 Deglutathionylation. Cell Rep, DOI: 10.1016/j.celrep.2019.08.072
Willis Fox O, Preston RJS, 2020 Jan, Molecular basis of protease-activated receptor 1 signaling diversity. J Thromb Haemost, DOI: 10.1111/jth.14643
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
Preston RJS, Lisman T, 2018 Mar, Extrahemostatic Functions of Platelets and Coagulation Factors. Semin Thromb Hemost, DOI: 10.1055/s-0037-1612624
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
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
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
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
Preston RJS, O'Donnell JS, 2017 Jul 27, Microbiome influences von Willebrand factor. Blood, DOI: 10.1182/blood-2017-06-789156
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
Heurich M, Preston RJ, O'Donnell VB, Morgan BP, Collins PW, 2016 Sep, Thrombomodulin enhances complement regulation through strong affinity interactions with factor H and C3b-Factor H complex. Thromb Res, DOI: 10.1016/j.thromres.2016.07.017
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
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
Hams E, Bermingham R, Wurlod FA, Hogan AE, O'Shea D, Preston RJ, Rodewald HR, McKenzie AN, Fallon PG, 2016 Feb, The helminth T2 RNase ω1 promotes metabolic homeostasis in an IL-33- and group 2 innate lymphoid cell-dependent mechanism. FASEB J, DOI: 10.1096/fj.15-277822
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
Kevane B, Donnelly J, D'Alton M, Cooley S, Preston RJ, Ní Ainle F, 2014 Jul, Risk factors for pregnancy-associated venous thromboembolism: a review. J Perinat Med, DOI: 10.1515/jpm-2013-0207
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
Gleeson EM, O'Donnell JS, Hams E, Ní Áinle F, Kenny BA, Fallon PG, Preston RJ, 2014 Jan, Activated factor X signaling via protease-activated receptor 2 suppresses pro-inflammatory cytokine production from lipopolysaccharide-stimulated myeloid cells. Haematologica, DOI: 10.3324/haematol.2013.086918
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
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
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
McGrath RT, McKinnon TA, Byrne B, O'Kennedy R, Terraube V, McRae E, Preston RJ, Laffan MA, O'Donnell JS, 2010 Apr 1, Expression of terminal alpha2-6-linked sialic acid on von Willebrand factor specifically enhances proteolysis by ADAMTS13. Blood, DOI: 10.1182/blood-2009-09-241547
Bridges DJ, Bunn J, van Mourik JA, Grau G, Preston RJ, Molyneux M, Combes V, O'Donnell JS, de Laat B, Craig A, 2010 Feb 18, Rapid activation of endothelial cells enables Plasmodium falciparum adhesion to platelet-decorated von Willebrand factor strings. Blood, DOI: 10.1182/blood-2009-07-235150
Ni Ainle F, Preston RJ, Jenkins PV, Nel HJ, Johnson JA, Smith OP, White B, Fallon PG, O'Donnell JS, 2009 Aug 20, Protamine sulfate down-regulates thrombin generation by inhibiting factor V activation. Blood, DOI: 10.1182/blood-2009-05-222109
Larkin D, de Laat B, Jenkins PV, Bunn J, Craig AG, Terraube V, Preston RJ, Donkor C, Grau GE, van Mourik JA, O'Donnell JS, 2009 Mar, Severe Plasmodium falciparum malaria is associated with circulating ultra-large von Willebrand multimers and ADAMTS13 inhibition. PLoS Pathog, DOI: 10.1371/journal.ppat.1000349
Preston RJ, Morse C, Murden SL, Brady SK, O'Donnell JS, Mumford AD, 2009 Mar, The protein C omega-loop substitution Asn2Ile is associated with reduced protein C anticoagulant activity. Br J Haematol, DOI: 10.1111/j.1365-2141.2008.07550.x
Preston RJ, Tran S, Johnson JA, Ní Áinle F, Harmon S, White B, Smith OP, Jenkins PV, Dahlbäck B, O'Donnell JS, 2009 Feb 27, Platelet factor 4 impairs the anticoagulant activity of activated protein C. J Biol Chem, DOI: 10.1074/jbc.M804703200
Cunningham MS, Preston RJ, O'Donnell JS, 2009 May, Does antithrombotic therapy improve survival in cancer patients? Blood Rev, DOI: 10.1016/j.blre.2008.10.002
Harmon S, Preston RJ, Ni Ainle F, Johnson JA, Cunningham MS, Smith OP, White B, O'Donnell JS, 2008 Nov 7, Dissociation of activated protein C functions by elimination of protein S cofactor enhancement. J Biol Chem, DOI: 10.1074/jbc.M802338200
Hochart H, Jenkins PV, Preston RJ, Smith OP, White B, O'Donnell J, 2008 Mar, Concentration-dependent roles for heparin in modifying lipopolysaccharide-induced activation of mononuclear cells in whole blood. Thromb Haemost, DOI: 10.1160/TH07-06-0424
Persson KE, Stenflo J, Linse S, Stenberg Y, Preston RJ, Lane DA, Rezende SM, 2006 Sep 5, Binding of calcium to anticoagulant protein S: role of the fourth EGF module. Biochemistry, DOI: 10.1021/bi0601151
Preston RJ, Ajzner E, Razzari C, Karageorgi S, Dua S, Dahlbäck B, Lane DA, 2006 Sep 29, Multifunctional specificity of the protein C/activated protein C Gla domain. J Biol Chem, DOI: 10.1074/jbc.M604966200
Mollica L, Preston RJ, Chion AC, Lees SJ, Collins P, Lewis S, Lane DA, 2006 Feb, Autoantibodies to thrombin directed against both of its cryptic exosites. Br J Haematol, DOI: 10.1111/j.1365-2141.2005.05894.x
Preston RA, Comello RJ, 2005 Nov-Dec, Viability of hospital-based radiography programs. Radiol Technol, DOI: 10.1111/j.1365-2141.2005.05894.x
Zanardelli S, Crawley JT, Chion CK, Lam JK, Preston RJ, Lane DA, 2006 Jan 20, ADAMTS13 substrate recognition of von Willebrand factor A2 domain. J Biol Chem, DOI: 10.1074/jbc.M508316200
Biguzzi E, Razzari C, Lane DA, Castaman G, Cappellari A, Bucciarelli P, Fontana G, Margaglione M, D'Andrea G, Simmonds RE, Rezende SM, Preston R, Prisco D, Faioni EM, Protein S Italian Team., 2005 Mar, Molecular diversity and thrombotic risk in protein S deficiency: the PROSIT study. Hum Mutat, DOI: 10.1002/humu.20136
Preston RJ, Villegas-Mendez A, Sun YH, Hermida J, Simioni P, Philippou H, Dahlbäck B, Lane DA, 2005 Jan, Selective modulation of protein C affinity for EPCR and phospholipids by Gla domain mutation. FEBS J, DOI: 10.1111/j.1432-1033.2004.04401.x

    • Bayer HealthCare Pharmaceuticals Hemophilia Award Program – International Special Project Awardee (2017).
    • Guest Editor – Seminars in Thrombosis and Haemostasis Special Issue – ‘Extra Haemostatic Roles for Platelets and Coagulation Factors’. (2017)
    • Associate Editor – Research and Practice in Thrombosis and Haemostasis (2016-present)
    • Associate Editor – Seminars in Thrombosis and Haemostasis. (2015-present)
    • Ad hoc invited reviewer for Blood, Journal of Biological Chemistry, Journal of Thrombosis and Haemostasis, Biochemistry, Thrombosis and Haemostasis, Vascular Pharmacology and Thrombosis Research and others (2006-present).
    • Scientific Secretary of Haematology Association of Ireland (2014-2017).
    • Science Foundation Ireland Career Development Awardee (2016).
    • Daiichi-Sankyo Irish Heart Foundation Bursary Award Winner (2016).
    • Bayer HealthCare Pharmaceuticals Hemophilia Award Program – International Early Career Investigator Award (2013)
    • Novo Nordisk Access-To-Insight International Research Prize
    • Haematology Association of Ireland Inaugural Scholar Award (2010).
    • Science Foundation Ireland Starting Investigator Research Grant Awardee (2009).
    • Health Research Board Research Fellowship Award (2007).