Core C (Mouse Modeling and Animal Development Core) will provide comprehensive support for generation and maintenance of wild type and mutant mouse strains and disease models for biological and therapeutic evaluation studies described in Projects 1-4. In-house generation of genetically altered mouse strains allows us to customize the design of mouse models to meet the specific needs of the Projects. Maintenance and breeding services will provide the most efficient and cost effective means of generating, maintaining, and distributing the multiple strains of mice needed for the Projects. The vast majority of our therapeutic trials planned for this P01 application are preceded by preclinical experimentation in mouse models. Thus, timely access to adequate numbers of these specialized strains is needed to adequately service the variety of collaborative pre-clinical projects that are essential for advancement to early stage clinical testing in patients. The core will therefore be actively involved in generation and characterization of novel transgenic and gene targeted mouse models that will facilitate the scientific goals of each of the Projects.
The specific aims of the Core C are 1) Breeding and characterization of transgenic or knockout models for antibody and cytokine mediated therapeutic evaluation;2) Generation of xenograft models including a human-PBL-SCID mouse model with EBV+ B cell lymphoma, syngeneic and xenogeneic models of disseminated leukemia, lymphoma and solid tumors and the generation of conditional knock-out models;3) Centralized mouse ordering, breeding, maintenance and distribution;4) Specialized services to each Projects as warranted. The proposed use of mouse models should provide new insights into disease pathogenesis, drug mechanism of action, and therapeutic efficacy of targeted agents for Project 1;in vivo validation of negative regulators of monocyte and macrophage FcyR signaling for Project 2;assessment of NK cell development, tolerance, and function in antibody dependent cellular cytotoxicity in Project 3;and the interaction of myeloid derived suppressor cells with other innate immune effector cells in Project 4. Thus, the Core C will form an integral part of this Program Project Grant by facilitating exploitation of transgenic, knockout, xenograft and other mouse models in translational research.

Public Health Relevance

Relevance;The Core C will enable all investigators on this Program Project to have access to a centralized and integrated mouse facility. Genetically engineered animal models often require specialized care and close monitoring by investigators to identify and maintain the needed phenotypes. Timeliness in serving the integrated Program Project is of paramount importance, especially in testing preclinical and clinical immune models. These issues, combined with the difficulty from a regulatory and physical standpoint for animals to travel between vivarium facilities, make it essential that investigators be provided with immediate access to needed mouse resources in a centralized facility.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA095426-11
Application #
8291543
Study Section
Special Emphasis Panel (ZCA1-RPRB-B (J1))
Project Start
2002-02-01
Project End
2017-08-31
Budget Start
2012-09-19
Budget End
2013-08-31
Support Year
11
Fiscal Year
2012
Total Cost
$248,855
Indirect Cost
$101,236
Name
Ohio State University
Department
Type
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Gautam, Shalini; Fatehchand, Kavin; Elavazhagan, Saranya et al. (2016) Reprogramming Nurse-like Cells with Interferon γ to Interrupt Chronic Lymphocytic Leukemia Cell Survival. J Biol Chem 291:14356-62
Mani, R; Yan, R; Mo, X et al. (2016) Non-immunosuppressive FTY720-derivative OSU-2S mediates reactive oxygen species-mediated cytotoxicity in canine B-cell lymphoma. Vet Comp Oncol :
Freud, Aharon G; Keller, Karen A; Scoville, Steven D et al. (2016) NKp80 Defines a Critical Step during Human Natural Killer Cell Development. Cell Rep 16:379-91
Duggan, Megan C; Jochems, Caroline; Donahue, Renee N et al. (2016) A phase I study of recombinant (r) vaccinia-CEA(6D)-TRICOM and rFowlpox-CEA(6D)-TRICOM vaccines with GM-CSF and IFN-α-2b in patients with CEA-expressing carcinomas. Cancer Immunol Immunother 65:1353-1364
Byrd, John C; Harrington, Bonnie; O'Brien, Susan et al. (2016) Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med 374:323-32
Markowitz, Joseph; Abrams, Zachary; Jacob, Naduparambil K et al. (2016) MicroRNA profiling of patient plasma for clinical trials using bioinformatics and biostatistical approaches. Onco Targets Ther 9:5931-5941
Latchana, Nicholas; Regan, Kelly; Howard, John Harrison et al. (2016) Global microRNA profiling for diagnostic appraisal of melanocytic Spitz tumors. J Surg Res 205:350-8
Scoville, Steven D; Mundy-Bosse, Bethany L; Zhang, Michael H et al. (2016) A Progenitor Cell Expressing Transcription Factor RORγt Generates All Human Innate Lymphoid Cell Subsets. Immunity 44:1140-50
McMichael, Elizabeth L; Jaime-Ramirez, Alena C; Guenterberg, Kristan D et al. (2016) IL-21 enhances natural killer cell response to cetuximab-coated pancreatic tumor cells. Clin Cancer Res :
Mundy-Bosse, Bethany L; Scoville, Steven D; Chen, Li et al. (2016) MicroRNA-29b mediates altered innate immune development in acute leukemia. J Clin Invest 126:4404-4416

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