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)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HL112309-03
Application #
8656800
Study Section
Special Emphasis Panel (ZHL1)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Emory University
Department
Type
DUNS #
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Batsuli, Glaivy; Deng, Wei; Healey, John F et al. (2016) High-affinity, non-inhibitory pathogenic C1 domain antibodies are present in patients with hemophilia A and inhibitors. Blood :
Zakas, Philip M; Brown, Harrison C; Knight, Kristopher et al. (2016) Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction. Nat Biotechnol :
Myers, David R; Qiu, Yongzhi; Fay, Meredith E et al. (2016) Single-platelet nanomechanics measured by high-throughput cytometry. Nat Mater :
Eubanks, Joshua; Baldwin, W Hunter; Markovitz, Rebecca et al. (2016) A subset of high-titer anti-factor VIII A2 domain antibodies is responsive to treatment with factor VIII. Blood 127:2028-34
Chao, B N; Baldwin, W H; Healey, J F et al. (2016) Characterization of a genetically engineered mouse model of hemophilia A with complete deletion of the F8 gene. J Thromb Haemost 14:346-55
Ciciliano, Jordan C; Sakurai, Yumiko; Myers, David R et al. (2015) Resolving the multifaceted mechanisms of the ferric chloride thrombosis model using an interdisciplinary microfluidic approach. Blood 126:817-24
Qiu, Yongzhi; Ciciliano, Jordan; Myers, David R et al. (2015) Platelets and physics: How platelets "feel" and respond to their mechanical microenvironment. Blood Rev 29:377-86
Kahle, Joerg; Orlowski, Aleksander; Stichel, Diana et al. (2015) Epitope mapping via selection of anti-FVIII antibody-specific phage-presented peptide ligands that mimic the antibody binding sites. Thromb Haemost 113:396-405
Mannino, Robert G; Myers, David R; Ahn, Byungwook et al. (2015) "Do-it-yourself in vitro vasculature that recapitulates in vivo geometries for investigating endothelial-blood cell interactions". Sci Rep 5:12401
Zakas, P M; Vanijcharoenkarn, K; Markovitz, R C et al. (2015) Expanding the ortholog approach for hemophilia treatment complicated by factor VIII inhibitors. J Thromb Haemost 13:72-81

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