Introduction Mouse models are routinely used in biomedical research as preclinical tools of investigation. For example, in the development of novel agents for the treatment of persons with hemophilia A, the hemophilia A mouse model is routinely used to demonstrate treatment proof of concept as well as investigate comparative immunogenicity. The hemophilia A mouse models, one generated by knockout of exon 16 and another by knockout of exon 17, were first developed in the laboratory of Dr. Haig Kazazian (1, 2). To date, there have been over 400 publications utilizing these animals and several biological agents in commercial development or currently marketed have been subjected to pre-clinical testing in these models. Although there are canine hemophilia models available to the biomedical research community, their numbers are extremely limited and typically these animals are only utilized for late stage preclinical testing. Therefore, the currently proposed projects only involve mouse studies. No support for large animals is requested at this time. Resources available to the Emory TRC-THD participants for the care and maintenance of mice in the proposed research are substantial. Emory University has animal facilities located in 8 buildings, on or near the main campus, including the Pediatric ECC building, where animals for this proposal will be housed and the experiments will be conducted. Additional breeding colonies are maintained in the Whitehead Building, also on the main campus. These two buildings have over 60 animal housing rooms, procedure rooms, modern animal surgeries, radiographic resources, diagnostic laboratories, and bio-containment facilities. There is an Animal Care Unit that ensures daily maintenance and routine animal care, including provision of proper housing. Sanitation and nourishment are provided based on the University's policy. This proposal will benefit from a specialized core rodent breeding services staffed by nine managers/supervisors and 42 technicians. In addition, a Veterinary Services Unit provides for the entire animal health care program. The components of this program include vendor surveillance, quarantine and isolation, preventive medicine, daily observation, treatment and intervention for injury or illness, health evaluations of sentinel animals, necropsy, histopathology, parasitology, microbiology, serology, hematology and blood chemistries. Additionally, the staff of the Laboratory Animal Medicine Unit can provide assistance with animal anesthesia, surgery, radiography and post-operative care. It is staffed by two faculty DVMs, two resident DVMs, and six veterinary technicians. Finally, Emory University is committed to providing a quality program of animal care in compliance with state and federal laws and the standards and polices of the Public Health Service. The standards of the program meet or exceed the federal Animal Welfare Act PL 89-544 (1966) and subsequent amendments and the documents entitled """"""""Guide for the Care and Use of Laboratory Animals"""""""" and """"""""Public Health Service Policy on Humane Care and Use of Laboratory Animals"""""""". Emory University has been continuously accredited campus wide by the Association for the Assessment and Accreditation of Laboratory Animal Care International (AAALAC) since 1992.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HL112309-02
Application #
8464241
Study Section
Special Emphasis Panel (ZHL1-CSR-C)
Project Start
Project End
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
2
Fiscal Year
2013
Total Cost
$268,464
Indirect Cost
$95,155
Name
Emory University
Department
Type
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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Zhang, Yun; Qiu, Yongzhi; Blanchard, Aaron T et al. (2018) Platelet integrins exhibit anisotropic mechanosensing and harness piconewton forces to mediate platelet aggregation. Proc Natl Acad Sci U S A 115:325-330
Healey, J F; Parker, E T; Lollar, P (2018) Identification of aggregates in therapeutic formulations of recombinant full-length factor VIII products by sedimentation velocity analytical ultracentrifugation. J Thromb Haemost 16:303-315
Batsuli, G; Ito, J; Mercer, R et al. (2018) Anti-C1 domain antibodies that accelerate factor VIII clearance contribute to antibody pathogenicity in a murine hemophilia A model. J Thromb Haemost 16:1779-1788
Qiu, Yongzhi; Ahn, Byungwook; Sakurai, Yumiko et al. (2018) Microvasculature-on-a-chip for the long-term study of endothelial barrier dysfunction and microvascular obstruction in disease. Nat Biomed Eng 2:453-463
Sakurai, Yumiko; Hardy, Elaissa T; Ahn, Byungwook et al. (2018) A microengineered vascularized bleeding model that integrates the principal components of hemostasis. Nat Commun 9:509
Brockman, Joshua M; Blanchard, Aaron T; Pui-Yan Ma, Victor et al. (2018) Mapping the 3D orientation of piconewton integrin traction forces. Nat Methods 15:115-118
Hansen, Caroline E; Myers, David R; Baldwin, W Hunter et al. (2017) Platelet-Microcapsule Hybrids Leverage Contractile Force for Targeted Delivery of Hemostatic Agents. ACS Nano 11:5579-5589
Zerra, Patricia E; Cox, Courtney; Baldwin, W Hunter et al. (2017) Marginal zone B cells are critical to factor VIII inhibitor formation in mice with hemophilia A. Blood 130:2559-2568
Kahle, Joerg; Orlowski, Aleksander; Stichel, Diana et al. (2017) Frequency and epitope specificity of anti-factor VIII C1 domain antibodies in acquired and congenital hemophilia A. Blood 130:808-816

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