Animal Models of Disease Core

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ANIMAL MODEL OF DISEASE CORE – PROJECT SUMMARY/ABSTRACT The Animal Model of Disease Core (AMDC) is a comprehensive shared resource that has served UVA Cancer Center researchers' needs for more than two decades. Mice are one of the most widely used animal models for cancer. While cancer researchers have successfully studied the molecular and cellular properties of cancer cells propagated in culture, increasingly mouse models of cancer provide a more physiologically relevant opportunity to investigate the interplay of cancer cells, the tumor microenvironment, and the host immune system. Mouse models provide opportunities to study the evolution of cancer progression from first mutations to metastasis, and the unique opportunity to assess the genetic and epigenetic events correlated with acquisition of drug resistance. Following guidance from the UVACC leadership, the AMDC was formed by integrating two pre-existing shared resources: the Genetically Engineered Murine Model (GEMM) Core, and the Preclinical Tumor Assessment and Imaging Core, which consisted of the Tumor Xenograft Model (TXM) and Molecular Imagining Core (MIC) sections. This merger was conducted with the goal of better integrating cancer animal model creation, analysis and imaging. The AMDC integrates genome engineering, tumor xenografting, and imaging technologies to efficiently produce and analyze cancer animal models for UVA Cancer Center investigators. Since the last CCSG renewal, the AMDC has made great strides in novel technology development and state- of-art instrument acquisition. The AMDC swiftly adopted the Crispr-Cas9 technology for genome editing which enables cancer animal model generation at an unprecedented speed with significantly lowered cost. The AMDC also greatly expanded their library of patient derived xenograft (PDX) tumor models of ovarian cancer, head and neck cancers, and prostate and kidney GU cancers. The ultimate goal of these PDX efforts is to generate several lines of highly clinically relevant cancer models to be made widely available to the UVA community of cancer investigators. The AMDC has upgraded its PET imaging program with the addition of a cyclotron, which was funded by an NIH-NCRR high end instrument grant. In 2011, the cyclotron was installed in the Life Sciences Annex (built with funds from UVA SOM) adjoining the Snyder Building in the Fontaine Research Park. The AMDC is administered under ORCA, led by Dr. Jay W. Fox, the UVA Cancer Center Associate Director for Laboratory Infrastructure. AMDC staff routinely interact with other Cancer Center shared resources in particular the Biomolecular Analysis Facility, Biostatistics, Advanced Microscopy Facility, and Biorepository and Tissue Research Facilities. The interactions with other shared resource facilities on behalf of AMDC users help make the AMDC a one-stop service provider. Many of the AMDC users are UVA Cancer Center members who benefit from a co-pay that reduces their charges. The AMDC also is supported by the School of Medicine, which further lowers the cost for the Cancer Center users. The AMDC is reviewed annually by the Cancer Center leadership and the School of Medicine Research Advisory Committee to determine the level of subsidy required to maintain a revenue neutral core. The AMDC is competitive in pricing, rapid in service turnout time, and provides guarantees matching or exceeding the standards set up by comparative shared resources around the country.