Helen Philippou
Senior Research Fellow
Cardiovascular and Diabetes Research
Qualifications: BSc (Hons), PhD
Email: H.Philippou@leeds.ac.uk
Telephone: 0113 343 7768
Research Area
Understanding mechanisms of thrombosis and development of novel safer antithrombotic therapeutics
Details
My research since 1992 has focused on understanding mechanisms of thrombosis, in particular to the coagulation pathway. Currently my group is looking into the discovery of novel therapeutics against thrombosis that will be taken orally and will have safer bleeding profiles than other antithrombotics currently available or in development. I am also interested in understanding novel mechanisms that regulate the activity of coagulation factors. In addition, we are investigating hyperhomocysteinemia with respect to understanding its role in clot formation and its stability. Overall, we have established many methodologies that enable us to investigate clot formation and its stability in vitro and in vivo. These methodologies are being used to understand the nature of protein-protein interactions and other mechanisms involved in the coagulation pathway with respect to blood clot formation and its ability to be lysed by the fibrinolyitc pathway.
Recent Projects
The Medical Research Council: Developmental Pathway Funding Scheme £980,000 Dr H Philippou (PI), Dr RAS Ariëns, Prof CWG Fishwick, Dr R Foster (Oct 2011-Sept 2013) Development of a novel anticoagulant with minimal bleeding risk.
The Medical Research Council £398,642 Dr RAS Ariëns, Dr H Philippou, Dr V Ridger (Apr 2010-Mar 2013) Role of factor XIII in fibrin clot structure and thrombosis
Circulation Foundation, Mary Davies Award £25,000 Dr RAS Ariëns, Dr H Philippou, Dr DJA Scott (Oct 2009-Sep 2010) Role of thrombin activatable fibrinilysis inhibitor in abdominal aortic aneurysm.
Yorkshire Concept: Proof of Commercialisation Concept £63,634 Commercial Development of a Novel Anticoagulant with Minimal Bleeding Risk Dr H Philippou (PI) (Mar 2010-Feb 2014)
Biomedical Health Research Centre, Problem solving fund £19,455 Dr H Philippou (PI), Dr RAS Ariëns, Prof CWG Fishwick, Dr R Foster (Aug 2009-Jul 2010) Development of a novel anticoagulant with minimal bleeding risk.
Yorkshire Forward Yorkshire Enterprise Fellowship (Personal Award) £10,000 Development of Novel Inhibitors against Thrombosis Dr H Philippou (PI) (May 2008-Nov2009)
British Heart Foundation Programme Grant £316,151 Prof PJ Grant, Dr H Philippou and Dr RAS Ariens (Oct2009-Sept 2011) Inhibition of factor XIII/fibrin interactions: impact on in vitro and in vivo thrombus formation
British Heart Foundation Project Grant £178,086 Dr H Philippou (PI), Prof PJ Grant, Dr R Pease and Dr V Ridger (Mar 2009-Feb 2012) Regulation of factor XIIIa activity
British Heart Foundation Project Grant £148,715 Dr H Philippou (PI), Dr R Ariëns and Prof J Scott (Sept 2008-Aug 2011) Homocysteinylation of End-Stage Coagulation Proteins: Effects on Fibrin Structure/Function in relation to Cardiovascular Risk
British Heart Foundation Project Grant £137,381 Dr R Ariens, Prof P Grant, Prof N Hooper, Dr H Philippou (Mar 07-Feb 10) Heterogeneity of plasmin inhibitor: origin, distribution and implications for cross-linking to fibrin and fibrinolytic potential
British Heart Foundation: Programme Grant £392,425 Prof PJ Grant, Dr H Philippou and Dr R Ariëns (Oct 2003-Sept 2008) Molecular analysis of factor XIII/fibrinogen interactions in the regulation of fibrin assembly
Diabetes UK Project Grant £149,138 Prof PJ Grant, Dr H Philippou and Dr E Dunn (Jul 2007-Jun 2010) Glycation of End-Stage Coagulation Proteins: Effects on Fibrin Structure/Function in relation to Cardiovascular Risk
Publications
Selected
Smith KA; Adamson PJ; Pease RJ; Brown JM; Balmforth AJ; Cordell PA; Ariens RAS; Philippou H; Grant PJ (2011) Interactions between factor XIII and the alpha C region of fibrinogen. BLOOD, 117 , pp. 3460-3468.
Mutch NJ; Engel R; de Willige SU; Philippou H; Ariens RAS (2010) Polyphosphate modifies the fibrin network and down-regulates fibrinolysis by attenuating binding of tPA and plasminogen to fibrin. BLOOD, 115 , pp. 3980-3988.
All
Scott DJA; Prasad P; Philippou H; Rashid ST; Sohrabi S; Whalley D; Kordowicz A; Tang Q; West RM; Johnson A; Woods J; Ajjan RA; Ariens RAS (2011) Clot Architecture Is Altered in Abdominal Aortic Aneurysms and Correlates With Aneurysm Size. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 31 , pp. 3004-3010.
Konings J; Govers-Riemslag JWP; Philippou H; Mutch NJ; Borissoff JI; Allan P; Mohan S; Tans G; ten Cate H; Ariens RAS (2011) Factor XIIa regulates the structure of the fibrin clot independently of thrombin generation through direct interaction with fibrin. BLOOD, 118 , pp. 3942-3951.
La Corte ALC; Ali M; Glowacki R; Jakubowski H; Ridger V; Pease R; Scott J; Ariens RA; Philippou H (2011) In vivo N-homocysteinylation of fibrinogen and its role in thrombosis. JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 9 , pp. 142-142.
de Willige SU; Miedzak M; Carter AM; Lisman T; Rosendaal FR; Grant PJ; Philippou H; Ariens RAS (2011) Proteolytic and genetic variation of the alpha-2-antiplasmin C-terminus in myocardial infarction. BLOOD, 117 , pp. 6694-6701.
Smith KA; Adamson PJ; Pease RJ; Brown JM; Balmforth AJ; Cordell PA; Ariens RAS; Philippou H; Grant PJ (2011) Interactions between factor XIII and the alpha C region of fibrinogen. BLOOD, 117 , pp. 3460-3468.
La Corte ALC; Philippou H; Ariens RAS (2011) ROLE OF FIBRIN STRUCTURE IN THROMBOSIS AND VASCULAR DISEASE. ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY: PROTEIN STRUCTURE AND DISEASES, VOL 83, 83 , pp. 75-127.
Ariens RAS; Ajjan R; Standeven KF; de Willige US; Mutch NJ; Philippou H (2010) Role of fibrin clot structure in susceptibility to lysis. JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 8 , pp. 6-6.
Mutch NJ; Engel E; de Willige US; Philippou H; Ariens RAS (2010) Polyphosphate modulates fibrin structure altering its susceptibility to lysis. JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 8 , pp. 15-15.
Konings J; Govers-Riemslag JWP; Philippou H; Mutch NJ; Tans G; Ariens RAS; ten Cate H (2010) The impact of coagulation Factor XII on clot structure and resistance to lysis. JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 8 , pp. 47-47.
Metassan S; Routledge MN; Lucking AJ; de Willige SU; Philippou H; Mills NL; Newby DE; Ariens RAS (2010) Fibrin clot structure remains unaffected in young, healthy individuals after transient exposure to diesel exhaust. PARTICLE AND FIBRE TOXICOLOGY, 7 .
Lucking AJ; Visvanathan A; Philippou H; Fraser S; Grant PJ; Connolly TM; Gardell SJ; Feuerstein GZ; Fox KAA; Booth NA; Newby DE (2010) Effect of the small molecule plasminogen activator inhibitor-1 (PAI-1) inhibitor, PAI-749, in clinical models of fibrinolysis. JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 8 , pp. 1333-1339.
Mutch NJ; Engel R; de Willige SU; Philippou H; Ariens RAS (2010) Polyphosphate modifies the fibrin network and down-regulates fibrinolysis by attenuating binding of tPA and plasminogen to fibrin. BLOOD, 115 , pp. 3980-3988.
de Willige SU; Standeven KF; Philippou H; Ariens RAS (2009) The pleiotropic role of the fibrinogen gamma ' chain in hemostasis. BLOOD, 114 , pp. 3994-4001.
De Willige SU; Philippou H; Ariens RAS (2009) Allele-specific alternative splicing; the tail of FXIII-B tells its own tale. JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 7 , pp. 1081-1083.
Dunn EJ; Philippou H; Ariens RAS; Grant PJ (2006) Molecular mechanisms involved in the resistance of fibrin to clot lysis by plasmin in subjects with type 2 diabetes mellitus. DIABETOLOGIA, 49 , pp. 1071-1080.
Lane DA; Philippou H; Huntington JA (2005) Directing thrombin. BLOOD, 106 , pp. 2605-2612.
Preston RJS; Villegas-Mendez A; Sun YH; Hermida J; Simioni P; Philippou H; Dahlback B; Lane DA (2005) Selective modulation of protein C affinity for EPCR and phospholipids by Gla domain mutation. FEBS JOURNAL, 272 , pp. 97-108.
Philippou H; Rance J; Myles T; Hall SW; Ariens RA; Grant PJ; Leung L; Lane DA (2003) Roles of low specificity and cofactor interaction sites on thrombin during factor XIII activation - Competition for cofactor sites on thrombin determines its fate. JOURNAL OF BIOLOGICAL CHEMISTRY, 278 , pp. 32020-32026.
Hermida J; Hurtado V; Villegas-Mendez A; Catto AJ; Philippou H (2003) Identification and characterization of a natural R96C EPCR variant. JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 1 , pp. 1850-1852.
Philippou H; Rance J; Myles T; Hall SW; Ariens RA; Grant PJ; Leung L; Lane DA (2003) Roles of low specificity and cofactor interaction sites on thrombin during factor XIII activation. Journal of Biological Chemistry, 278 (34), pp. 32020-32026.
Ariens RAS; Philippou H; Nagaswami C; Weisel JW; Lane DA; Grant PJ (2000) The factor XIII V34L polymorphism accelerates thrombin activation of factor XIII and affects cross-linked fibrin structure. Blood, 96 (3), pp. 988-995.
Philippou H; Adami A; Davidson SJ; Pepper JR; Burman JF; Lane DA (2000) Tissue factor is rapidly elevated in plasma collected from the pericardial cavity during cardiopulmonary bypass. Thrombosis and Haemostasis, 84 (1), pp. 124-128.
Al-Obaidi MK; Philippou H; Stubbs PJ; Adami A; Amersey R; Noble MM; Lane DA (2000) Relationships between homocysteine, factor VIIa, and thrombin generation in acute coronary syndromes. Circulation (Baltimore), 191 (4), pp. 372-377.
Teaching Commitments
Supervision of PhD Students SSC Literature Reviews Undergraduate Research projects
Widening Participation
I am Commercialisation Lead of the Leeds’ Multidisciplinary Cardiovascular Research Centre (MCRC) and LIGHT Lead for Enterprise and Innovation.
In addition to generation of IP with respect to my own group's research, I am also engaging other academics to identify aspects of their own research that has commercialisation potential.