The purpose of this resource grant is to maintain and create dogs with hemophilia A, hemophilia B, von Willebrand disease (VWD), and FVII deficiency for independent and collaborative research. Our objectives are: 1) To maintain a breeding colony of well-characterized dogs with inherited bleeding disorders at the Francis Owen Blood Research Laboratory (FOBRL), University of North Carolina, Chapel Hill;2) To produce purpose-bred, affordable research animals with these bleeding disorders in a cost effective manner;3) To provide specialized support services for research projects using these dogs including canine blood banking and coagulation analyses, and 4) To acquire and characterize new canine models of inherited bleeding disorders. These dogs, identified by Dr. Kenneth M. Brinkhous, model human hemophilias and VWD and have been maintained for >60 years at UNC largely through NIH support. Research using the FOBRL dogs has more than doubled during the past 30 years and has led to discoveries that have revolutionized the treatment of inherited and acquired bleeding and thrombotic disorders. Many therapeutic agents were developed and tested in these dogs and then successfully translated into the clinic. Thus many advisory boards recommend these dogs as essential for pre-clinical testing of new treatments for these inherited bleeding disorders. Major accomplishments during the past 5 years include 37 peer-reviewed publications while building new and completely renovating existing animal facilities. A highly trained staff at the FOBRL has years of experience maintaining these dogs with a dedicated canine blood bank, developing canine coagulation assays, conducting investigations, and collaborating successfully with investigators worldwide. Current research includes in vivo validation of new treatments for bleeding, developing hemophilia A dogs with inhibitors, and determining the acute and chronic sequelae of gene therapy on genetic diseases. This grant is the only support for maintenance of this colony. Without this grant, new research would be very difficult and expensive to initiate and the survival of this colony would be jeopardized. This Resource Grant is essential to assure the survival of this colony in an established, successful environment.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Resource-Related Research Projects (R24)
Project #
Application #
Study Section
Special Emphasis Panel (ZHL1-CSR-A (M2))
Program Officer
Link, Rebecca P
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Fiscal Year
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University of North Carolina Chapel Hill
Internal Medicine/Medicine
Schools of Medicine
Chapel Hill
United States
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Sauna, Zuben E; Lozier, Jay N; Kasper, Carol K et al. (2015) The intron-22-inverted F8 locus permits factor VIII synthesis: explanation for low inhibitor risk and a role for pharmacogenomics. Blood 125:223-8
Sherman, Alexandra; Schlachterman, Alexander; Cooper, Mario et al. (2014) Portal vein delivery of viral vectors for gene therapy for hemophilia. Methods Mol Biol 1114:413-26
Pope, Ava G; Wu, Gongting; McWhorter, Frances Y et al. (2013) Contrast-enhanced imaging of SPIO-labeled platelets using magnetomotive ultrasound. Phys Med Biol 58:7277-90
Lozier, Jay N; Nichols, Timothy C (2013) Animal models of hemophilia and related bleeding disorders. Semin Hematol 50:175-84
Sabatino, Denise E; Nichols, Timothy C; Merricks, Elizabeth et al. (2012) Animal models of hemophilia. Prog Mol Biol Transl Sci 105:151-209
Nichols, T C; Franck, H W G; Franck, C T et al. (2012) Sensitivity of whole blood clotting time and activated partial thromboplastin time for factor IX: relevance to gene therapy and determination of post-transfusion elimination time of canine factor IX in hemophilia B dogs. J Thromb Haemost 10:474-6
Scola, Mallory R; Baggesen, Leslie M; Nichols, Tim C et al. (2012) A review of current methods for assessing hemostasis in vivo and introduction to a potential alternative approach. Thromb Res 129 Suppl 2:S57-61
Sabatino, Denise E; Lange, Amy M; Altynova, Ekaterina S et al. (2011) Efficacy and safety of long-term prophylaxis in severe hemophilia A dogs following liver gene therapy using AAV vectors. Mol Ther 19:442-9
Knudsen, T; Kristensen, A T; Nichols, T C et al. (2011) Pharmacokinetics, pharmacodynamics and safety of recombinant canine FVIIa in a study dosing one haemophilia A and one haemostatically normal dog. Haemophilia 17:962-70
Knudsen, Tom; Kjalke, Marianne; Tranholm, Mikael et al. (2011) Development of a flow cytometric assay for detection of coated platelets in dogs and evaluation of binding of coated platelets to recombinant human coagulation factor VIIa. Am J Vet Res 72:1007-14

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