Untitled Document

 

Dr. David Lillicrap MD, FRCPC

 

Department of Pathology
& Molecular Medicine 
Richardson Laboratory
Queen's University
Kingston, Ontario
K7L 3N6, CANADA

TEL: (613) 548-1304
FAX: (613) 548-1356
e-mail: lillicrap (at) cliff.path.queensu.ca


Position

Professor, Department of Pathology and Molecular Medicine
Canada Research Chair in Molecular Hemostasis
Career Investigator of the Heart and Stroke Foundation of Ontario

Education

St. Mary's Hospital Medical School, University of London, United Kingdom


Selected Administrative Appointments

World Health Organization/World Federation of Hemophilia Working Group on Genetic Diagnosis in the Hemophilias, 1991-1992
International Society for Thrombosis and Haemostasis Scientific Standardisation Committee on VWD, 1998-Present
Member, Medical and Scientific Advisory Council (MASAC) for the National Hemophilia Foundation (USA), 2002-Present
Member, Gene Therapy Working Group of the National Hemophilia Foundation (USA), 2000-
Present
International Society for Thrombosis and Haemostasis Council of the Scientific Standardisation Committee, 2002-Present


Research Interests

All of the research being undertaken by this group relates to molecular aspects of the hemostatic (coagulation) system. In the normal physiological state, a delicate balance is preserved between pro- and anti-coagulant factors that contributes to the maintenance of the normal circulation. When this balance is disrupted, bleeding or thrombosis occurs.

This research program utilizes the potential of molecular genetics and molecular biology to address a variety questions relating to pathological hemostasis. The studies range from an investigation of the mechanisms regulating production of the adhesive hemostatic protein, von Willebrand Factor, to the development of strategies for gene therapy for the inherited bleeding disease, hemophilia.



Publications

2013

Kahlon A, Grabell J, Tuttle A, Engen D, Hopman W, Lillicrap D, James P.
Quantification of perioperative changes in von Willebrand factor and factor VIII during elective orthopaedic surgery in normal individuals. Haemophilia May 28 Epub ahead of print, 2013.

Rydz N, Swystun LL, Notley C, Paterson AD, Riches JJ, Sponagle K, Boonyawat B, Montgomery RR, James PD, Lillicrap D.
The C-type lectin receptor CLEC4M binds, internalizes and clears von Willebrand factor and contributes to the variation in plasma von Willebrand factor levels.
Blood. Mar 25. Epub ahead of print, 2013.

James PD, Lillicrap D, Mannucci PM.
Alloantibodies in von Willebrand Disease.
Blood. Jan 7. Epub ahead of print, 2013.

Lillicrap D.
The future of hemostasis management.
Ped Blood & Cancer 60 Suppl 1, S44-7, 2013.

Golder M, Mewburn J, Lillicrap D.
In vitro and in vivo evaluation of the effect of elevated factor VIII on the thrombogenic process.
Thromb Haemost 109(1):53-60, 2013.

Bowman M, Tuttle A, Notley C, Brown C, Tinlin S, Deforest M, Leggo J, Blanchette VS, Lillicrap D, James P;
Association of Hemophilia Clinic Directors of Canada.
The genetics of Canadian type 3 von Willebrand disease: further evidence for co-dominant inheritance of mutant alleles.
J Thromb Haemost. 11(3):512-20, 2013.

James PD, Lillicrap D.
The molecular characterization of von Willebrand disease: good in parts.
Br J Haematol. 161(2):166-76, 2013.

Lillicrap,D.
Molecular testing for disorders of hemostasis.
Int J Lab Hematol. 35(3):290-6, 2013.

2012

Webert KE, Rivard GE, Teitel J, Carcao M, Lillicrap D, St-Louis J, Walker IR.
Low prevalence of inhibitor antibodies in the Canadian haemophilia population.
Haemophilia 18(3):e254-9, 2012.

Foley JH, Petersen KU, Rea CJ, Harpell L, Powell S, Lillicrap D, Nesheim ME, Sorensen B.
Solulin increases clot stability in whole blood from humans and dogs with hemophilia.
Blood, 119(15):3622-8, 2012.

Pruss CM, Golder M, Bryant A, Hegadorn C, Haberichter S, Lillicrap D.
Use of a mouse model to elucidate the phenotypic effects of the von Willebrand factor cleavage mutants, Y1605A/M1606A and R1597W. J Thromb Haemost 10(5):940-50, 2012.

James PD, Lillicrap D.
von Willebrand disease: clinical and laboratory lessons learned from the large von Willebrand disease studies.
Am J Hematol 87 Suppl 1, S4-11, 2012.

Lillicrap D.
The World Federation of Hemophilia and Research.
Haemophilia 18 Suppl 4, 24-7, 2012.

Blomback M, Eikenboom J, Lane D, Denis C, Lillicrap D.
von Willebrand disease biology.
Haemophilia 18 Suppl 4, 141-7, 2012.

Berntorp E, Peake I, Budde U, Laffan M, Montgomery R, Windyga J, Goodeve A, Petrini P, von Depka M, Miesbach W, Lillicrap D, Federici AB, Lassila R, White G.
von Willebrand's disease: A report from a meeting in the Aland islands.
Haemophilia 18 Suppl 6, 1-13, 2012.

Rae C, Furlong W, Horsman J, Pullenayegum E, Demers C, St-Louis J, Lillicrap D, Barr R.
Bleeding disorders, menorrhagia and iron deficiency: impacts on health-related quality of life.
Haemophilia Epub ahead of print Sept 21 2012.

Lillicrap D.
A complex substitute: antibody therapy for hemophilia.
Nature Med 18(10):1460-1, 2012.

2011

Coutu, DL, Cuerquis J, El Ayoubi R, Forner KA, Roy R, François M, Griffith M, Lillicrap, D, Yousefi AM, Blostein MD, Galipeau J.
Hierarchial scaffold design for mesenchymal stem cell-based gene therapy of hemophilia B.
Biomaterials 32:295-305, 2011.

Darwish, H, Mundell G, Engen D, Lillicrap D, Silva M, James P.
Early intraoperative blood collection does not affect complete blood counts, von Willebrand factor or factor VIII levels in normal children.
J Pediatr Hematol Oncol 33(1):47-9, 2011.

Qadura M, Waters B, Burnett E, Chegeni R, Hough C, Othman M, Lillicrap D.
Immunoglobulin isotypes and functional anti-FVIII antibodies in response to FVIII treatment in Balb/c and C57BL/6 haemophilia A mice.
Haemophilia 17(2):288-95, 2011.

Hamilton A, Ozelo M, Leggo J, Notley C, Brown H, Frontroth JP, Angelillo-Scherrar A, Baghaei F, Enayat SM, Favaloro, E., Lillicrap D, Othman M.
Frequency of platelet type versus type 2B von Willebrand disease. An International registry-based study.
Thromb Haemost 105(3):501-8, 2011.

Chegeni R, Vickars L, Favaloro EJ, Lillicrap D, Othman M.
Functional analysis of three recombinant A-VWF domain mutants in comparison to wild-type and plasma-derived VWF facilitates subtyping in type 2 von Willebrand disease.
Thromb Res 127(2):161-6, 2011.

Matsui H, Hegadorn C, Ozelo M, Burnett E, Tuttle A, Labelle A, McCray PB Jr., Naldini L, Brown B, Hough C, Lillicrap D.
A microRNA-regulated and GP64-pseudotyped Lentiviral vector mediates stable expression of FVIII in a murine model of hemophilia A.
Mol Ther 19(4):723-30, 2011.

DiPaola J, Lillicrap D.
Challenges and innovations in the treatment of bleeding disorders.
Thromb Res 127 Suppl 1:S1-2, 2011.

James PD, Lillicrap D.
The diagnosis and management of von Willebrand disease in Canada
Semin Thromb Hemost. 37(5):522-7, 2011.

Hubbard AR, Hamill M, Beeharry M, Bevan SA, Heath AB; SSC sub-committee on von Willebrand factor of ISTH.
Value assignment of the WHO 2nd International Standard von Willebrand factor, concentrate (09/182).
J Thromb Haemost. 9(8):1638-40, 2011.

Robertson JD, Yenson PR, Rand ML, Blanchette VS, Carcao MD, Notley C, Lillicrap D, James PD.
Expanded phenotype-genotype correlations in a pediatric population with type 1 von Willebrand disease.
J Thromb Haemost. 9(9):1752-60, 2011.

Viuff D, Barrowcliffe T, Saugstrup T, Ezban M, Lillicrap D.
International comparative field study of N8 evaluating factor VIII assay performance.
Haemophilia. 17(4):695-702, 2011.

Gupta M, Lillicrap D, Stain AM, Friedman KD, Carcao MD.
Therapeutic consequences for misdiagnosis of type 2N von Willebrand disease.
Pediatr Blood Cancer. 1;57(6):1081-3, 2011.

Pruss CM, Golder M, Bryant A, Hegadorn CA, Burnett E, Laverty K, Sponagle K, Dhala A, Notley C, Haberichter S, Lillicrap D.
Pathologic mechanisms of type 1 VWD mutations R1205H and Y1584C through in vitro and in vivo mouse models.
Blood. 117(16):4358-66, 2011.

Hang MX, Blanchette VS, Pullenayegum E, McLimont M, Feldman BM; Canadian Hemophilia Primary Prophylaxis Study Group
Age at first joint bleed and bleeding severity in boys with severe hemophilia A: Canadian Hemophilia Primary Prophylaxis Study.
J Thromb Haemost. 9(5):1067-9, 2011.

Coutu DL, Cuerquis J, El Ayoubi R, Forner KA, Roy R, François M, Griffith M, Lillicrap D, Yousefi AM, Blostein MD, Galipeau J.
Hierarchical scaffold design for mesenchymal stem cell-based gene therapy of hemophilia B.
Biomaterials. 32(1):295-305, 2011.

2010

Biss TT, Blanchette VS, Clark DS, Bowman M, Wakefield C, Silva M, James PD and Rand ML. 
Quantitation of Bleeding Symptoms in Children with von Willebrand Disease (VWD): Use of a Standardized Pediatric Bleeding Questionnaire. 
Online accepted J Thromb Haemost February 2, 2010. DOI: 10.1111/j.1538-7836.2010.03796
 
M. Bowman, W.M. Hopman, D. Rapson, D. Lillicrap and P. James. 
The Prevalence of Symptomatic VWD in Primary Care Practice.
J Thromb Haemost 2010; 8:213-216

Reipert B, Arruda V, Lillicrap D.
Animal models of inhibitors.
Haemophilia 16 Suppl 5:47-53, 2010.

Bowman M, Hopman WM, Rapson D, Lillicrap D, Silva M, James P.
A prospective evaluation of the prevalence of symptomatic von Willebrand disease (VWD) in a pediatric primary care population.
Pediatr Blood Cancer 55:171-3, 2010.

Golder M, Pruss CM, Hegadorn C, Mewburn J, Laverty K, Sponagle K, Lillicrap D.
Mutation-specific hemostatic variability in mice expressing common type 2B von Willebrand disease substitutions.
Blood 115:4862-9, 2010.

Lillicrap D.
Improvements in factor concentrates.
Curr Opin Hematol 17:393-7, 2010.

Othman M, Chirinian Y, Brown C, Notley C, Hickson N, Hampshire D, Buckley S, Waddington S, Parker AL, Baker A, James P, Lillicrap D
Functional characterization of a 13 bp deletion (c.-1522_11510del13) in the promoter of the von Willebrand factor gene in type 1 von Willebrand disease.
Blood 116:3645-3652, 2010.

Thakur A, Sengupta R, Matsui H, Lillicrap D, Jones K, Hortelano G.
Characterization of viability and proliferation of alginate-poly-L-lysine-alginate encapsulated myoblasts using flow cytometry.
J Biomed Mater Res B Appl Biomater 94:296-304, 2010.

Rodeghiero F, Tosetto A, Abshire T, Arnold DM, Coller B, James P. Neunert C, Lillicrap D; on behalf of the ISTH/SSC Joint VWF and Perinatal/Pediatric Hemostasis Subcommittees Working Group
ISTH/SCC Bleeding Assessment Tool: A standardized Questionnaire and a Proposal for a New Bleeding Score for Inherited Bleeding Disorders.
J. Thromb Haemost 8:2063-2065, 2010.

Finn JD, Ozelo MC, Sabatino DE, Franck HW, Merricks EP, Crudele JM, Zhou S, Kazazian HH, Lillicrap D, Nichols TC, Arruda VR
Eradication of neutralizing antibodies to factor VIII in canine hemophilia A following liver gene therapy.
Blood 116:5842-5845, 2010.

Othman M, Powell S, Hopman, WM, Lillicrap D
Variability of thromboelastographic responses following the administration of rFVIIa to haemophilia A dogs supports the individualization of therapy with a global test of haemostasis
Haemophilia 16(6):919-25, 2010.

2009

James, P., Lillicrap, D.
The role of molecular genetics in diagnosing von Willebrand disease.
Semin. Thromb. Hemost. 34(6):502-8, 2009.

Lillicrap, D.
The improved factor concentrate
Haemostaseologie 28(1):71-3, 2009.

Waters B, Qadura M, Burnett E, Chegeni R, Labelle A, Thompson P, Hough C, Lillicrap D.
Anti-CD3 therapy in hemophilia A mice prevents factor VIII inhibitor formation by increasing regulatory CD4+CD25+ T cells.
Blood, 113:193-203, 2009.

Vincent AM, Lillicrap D, Boulanger A, Meilleur C, Amesse C, St-Louis J, Rivard GE.
Non-neutralizing anti-FVIII antibodies: different binding specificity to different recombinant FVIII concentrates.
Haemophilia. 2009 Jan;15(1):374-6

Qadura M, Waters B, Burnett E, Chegeni R, Bradshaw S, Hough C, Othman M, Lillicrap
Recombinant and plasma-derived factor VIII products induce distinct splenic cytokine microenvironments in hemophilia A mice.D.
Blood. 2009 May 1. [Epub ahead of print]

Matsui H, Shibata M, Brown B, Labelle A, Hegadorn C, Andrews C, Chuah M, Vandendriessche T, Miao CH, Hough C, Lillicrap D.
A murine model for induction of long-term immunologic tolerance to factor VIII does not require persistent detectable levels of plasma factor VIII and involves contributions from Foxp3+ T regulatory cells.
Blood. 2009 May 20. [Epub ahead of print]

2008

Stakiw J, Bowman M, Hegadorn C, Pruss C, Notley C, Groot E, Lenting P, Lillicrap D, James PD.
The Effect of Exercise on Individuals with Type 1 and Type 2B von Willebrand Disease (VWD).
J.Thromb.Haemostas. 6:90-96, 2008

Prasad S, Lillicrap D, Labelle A, Knappe S, Keller T, Burnett E, Powell S, Johnson KW.
Efficacy and Safety of a New-Class of Hemostatic Drug Candidate, AV513, in Hemophilia A Dogs
Blood, 111:272-279, 2008.

Rubinger M, Lillicrap D, Rivard GE, Teitel J, Carcao M, Hensman C, Walker I. The association of Hemophilia Clinic Directors of Canada.
A prospective surveillance study of factor VIII inhibitor development in the Canadian hemophilia A population following the switch to a recombinant factor VIII product formulated with sucrose.
Haemophilia 14:281-6, 2008
.


Hough C, Cameron C, Notley C, Brown C, O’Brien L, Keightley A,M, Berber E, Lillicrap D.
Influence of a GT Repeat Element on Shear Stress-Responsiveness of the VWF Gene Promoter.
J.Thromb.Haemost. 6 (7):1183-70, 2008

Pruss,C.M., Notley, C.R.P., Hegadorn, C.A., O'Brien, L.A., Lillicrap, D.
ADAMTS13 Cleavage Efficiency is Altered by Polymorphic and Mutagenic Sequence Changes in the A1 and A2 Domains of von Willebrand Factor (VWF).
Br.J.Haematol 143:552-558, 2008.

James PD, Stakiw J, Leggo J, Walker I, Lillicrap D.
A case of non-resolving hemophilia B Leyden in a 42-year-old male (F9 promoter + 13 A>G)
J Thromb Haemost. 6(5):885-6, 2008.

Robertson J, Lillicrap D, James PD.
von Willebrand disease.
Pediatr Clin North Am. 55(2):377-92, 2008.

Pipe SW, High KA, Ohashi K, Ural AU, Lillicrap D.
Progress in the molecular biology of inherited bleeding disorders.
Haemophilia. 14 Suppl 3:130-7, 2008.

Collins PW, Cumming AM, Goodeve AC, Lillicrap D.
Type 1 von Willebrand disease: application of emerging data to clinical practice.
Haemophilia. 14(4):685-96, 2008.

Qadura M, Othman M, Waters B, Chegeni R, Walker K, Labelle A, Hough C, Lillicrap D.
Reduction of the immune response to Factor VIII mediated through tolerogenic Factor VIII presentation by immature dendritic cells.
J.Thromb.Haemostas. 6:2095-104, September 2008.

Bowman M, Mundell G, Grabell J, Hopman WM, Rapson D, Lillicrap D, James P.
Generation and validation of the Condensed MCMDM-1VWD Bleeding Questionnaire for von Willebrand disease.
J Thromb Haemost.6:2062-6, 2008.

2007

James PD, Notley C, Hegadorn C, Leggo J, Tuttle A, Tinlin S, Brown C, Andrews C, Labelle A, Chirinian Y, O’Brien L, Othman M, Rivard G, Rapson D, Hough C, Lillicrap D.
The Mutational Spectrum of Type 1 von Willebrand Disease: Results from a Canadian Cohort Study.
Blood 109:145-54, 2007.

Othman M, Labelle A, Mazzetti I, Elbatarny H and Lillicrap D.
Adenovirus-induced thrombocytopenia: The role of P-selectin and von Willebrand factor in mediating accelerated platelet clearance.
Blood 109:2832-39, 2007.

Matsui H, Shibata M, Brown B, Labelle A, Hegadorn C, Andrews C, Hebbel RP, Galipeau J, Hough C, Lillicrap D.
Ex vivo gene therapy for Hemophilia A that enhances safe delivery and sustained in vivo FVIII expression from lentivirally-engineered endothelial progenitors.
Stem Cells, 25:2660-2669, 2007.

Barnes C, Blanchette V, Lillicrap D, Mann K, Stain AM, Leggo J, Carcao M.
Different clinical phenotype in triplets with Haemophilia A
Haemophilia 13:202-5, 2007.

Lenting PJ, de Groot PG, Denis CV, Marx I, Lillicrap D, Pruss C, Vanhoorelbeke K, De Meyer SF.
Correction of the bleeding time in von Willebrand factor (VWF)-deficient mice using murine VWF
Blood, 109: 2267-2268, 2007.


James PD, Notley C, Hegadorn C, Poon MC, Walker I, Rapson D, Association of Hemophilia Clinic Directors of Canada, Lillicrap D.
Challenges in Defining Type 2M von Willebrand Disease: Results from a Canadian Cohort Study.
J.Thromb.Haemostas. 5:1914-1922, 2007.

Lillicrap D.
Von Willebrand disease - phenotype versus genotype: deficiency versus disease.
Thromb Res. 120 Suppl 1:S11-6, 2007.

Othman M, Lillicrap D.
Distinguishing between non-identical twins: platelet type and type 2B von Willebrand disease.
Br J Haematol. 138(5):665-6, 2007.

Pierce GF, Lillicrap D, Pipe SW, Vandendriessche T.
Gene therapy, bioengineered clotting factors and novel technologies for hemophilia treatment.
J Thromb Haemost. 5(5):901-6, 2007.

Lillicrap D.
Inducing Tregs with hepatic gene therapy .
Blood 110: 1089, 2007.

2006

van Damme A, Thorrez L, Ma L, Vandenburgh H, Eyckmans J, Dell’accio F, De Bari C, Luyten F, Lillicrap D, Coleen D.
Efficient lentiviral transduction and improved engraftment of human bone marrow mesenchymal cells
Stem Cells 24:896-907, 2006.

Roland K, Rapson D, Lillicrap D, James P.
The value of genetic testing for Type 2B von Willebrand Disease.
Clin.Lab Haem 28:17-21, 2006.

James PD, Paterson AD, Notley C, Hegadorn C, Tinlin C, Brown C, Tuttle A, Association of Hemophilia Clinic Directors of Canada, Lillicrap D.
Genetic linkage and association analysis in Type 1 von Willebrand Disease (VWD): Results from the Canadian Type 1 VWD Study.
J.Thromb.Hemost. 4:783-92, 2006.

Lillicrap D, Nair SC, Srivastava A, Rodeghiero F, Pabinger I, Federici AB.
Laboratory issues in bleeding disorders.
Haemophilia 12 Suppl 3:68-75, 2006.

Lillicrap D, Vandendriessche T, High K.
Cellular and genetic therapies for haemophilia.
Haemophilia. 12 Suppl 3:36-41, 2006.

Dimichele D, Chuansumrit A, London AJ, Thompson AR, Cooper CG, Killian R
Ross, LF, Lillicrap D, Kimmelman J.
Ethical issues in haemophilia.
Haemophilia. 12 Suppl 3:30-5, 2006.

Jiang H, Lillicrap D, Patarroyo-White S, Liu T, Qian X, Scallan CD, Powell S, Keller T, McMurray M, Labelle A, Nagy D, Vargas JA, Zhou S, Couto LB, Pierce GF.
Multi-year Therapeutic Benefit of AAV Serotypes 2, 6 and 8 Delivering Factor VIII to Hemophilia A Mice and Dogs.
Blood 108:107-15, 2006.

James P and Lillicrap D.
Genetic Testing for von Willebrand Disease: The Canadian Experience
Seminars in Thrombosis and Haemostasis, 32:546-52, 2006.

Berber E, Leggo J, Brown C, Berber E, Gallo N, Feilotter, H, Lillicrap D
DNA Microarray Analysis for the Detection of Mutations in Hemophilia A.
Journal of Thrombosis and Haemostasis, 4:1756-62, 2006

Rawle FE, Pratt KP, Labelle A, Weiner HL, Hough C, Lillicrap D.
Induction of Partial Immune Tolerance to Factor VIII Through Prior Mucosal Exposure to the Factor VIII C2 Domain.
Journal of Thrombosis and Haemostasis, 4:2172-9, 2006.

Sadler JE, Budde U, Eikenboom JC, Favaloro EJ, Hill FG, Holmberg L, Ingerslev J, Lee CA, Lillicrap D, Mannucci PM, Mazurier C, Meyer D, Nicols WL, Nishino M, Peake IR, Rodeghiero F, Schneppenheim R, Ruggeri ZM, Srivastava A, Montgomery RR, Federici AB, The Working Party on von Willebrand Disease classification.
Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.
J Thromb Haemost 4:2103-14, 2006.

Lee CA, Lillicrap D, Astermark J.
Inhibitor development in hemophiliacs; the roles of genetic versus environmental factors.
Semin Thromb Hemost 32 Suppl 2:10-4, 2006.

Feldman BM, Pai M, Rivard GE, Israels S, Poon M-C, Demers C, Robinson S, Luke KH, Wu J, Gill K, Lillicrap D, Babyn P, McLimont M, Blanchette VS. Association of Hemophilia Clinic Directors of Canada Prophylaxis Study Group
Tailored prophylaxis in severe hemophilia A: interim results from the first 5 years of the Canadian Hemophilia Primary Prophylaxis Study (CHPS).
J Thromb Hemost 4:1228-36, 2006.

Barnes C, Lillicrap D, Pazmino-Canizares J, Blanchette, VS, Stain, AM, Clark, D, Hensmen, C, Carcao, M
Pharmacokinetics of recombinant Factor VIII (Kogenate-FS) in children and causes of inter patient pharmacokinetic variability. Haemophilia, 12 Suppl 4:40-9, 2006.

Lillicrap D.
The Role of Immunomodulation in the Management of Factor VIII Inhibitors
Hematology Am Soc Hematol Educ Program 421-5, 2006.