Core C: Animal Modeling and Imaging

CORE C - ANIMAL MODELING AND IMAGING PROJECT SUMMARY Core C supports all projects within the Program by providing access to sophisticated organoid-based animal models, small-animal imaging technologies, histopathology, and imaging of organoid and tumor samples. These services enable Program investigators to obtain insights into molecular and cellular mechanisms driving tumor progression, therapy response, and metastasis. Core C will assist with the design of animal experiments and support live animal imaging from classical bioluminescence imaging (BLI) to state-of-the-art imaging technologies, available only in a limited number of locations worldwide, such as small-animal positron emission tomography (PET) and single-photon emission computed tomography (SPECT). The Core will also support imaging with customized reporters for different cell signaling pathways. Histopathological services will be provided through a consultant agreement with a world-class pathologist specializing in mouse models of cancer. Finally, the Core will support immunolabeling of fixed organoids and tumor tissues, including support for whole- mount 3-dimensional (3D) volume scanning with antibody labeling and for multiplex immunohistochemistry. During the upcoming period of requested support, Core C proposes to support Program investigators through three aims. First, the program will provide assistance with animal modeling using transplantation with cancer cell lines and organoid-derived cancer cells. Organoid-based animal modeling requires optimization for each line to achieve optimal dissociation of cells before injection. Second, the core will provide Program investigators with tools to track tumor growth, metastasis, and therapy responses by assisting with small-animal BLI, ultrasound, PET, SPECT, and computed tomography (CT) imaging. Conducting imaging experiments with PET, SPECT, and CT requires not only sophisticated imaging equipment and reporters but also considerable expertise. Third, the core will assist with the analysis of tissues from animals, from histopathological evaluations to standard immune labeling, multiplex immunohistochemistry, and state-of-the-art 3D volume reconstruction with antibody labeling. Finally, Core C will assist with the use of advanced imaging software, including Image J (NIH) and Imaris (Bitplane). New in this renewal is support for CT, PET, and SPECT imaging in live animals and multiplex immunohistochemistry and 3D volume reconstruction on fixed organoid and tissue samples. Together, Core C provides a comprehensive platform for animal modeling and imaging, covering all necessary approaches for characterizing tumor growth in vivo. A Core that enables program investigators access to these technologies is essential as most of the services supported by the Core require specialized expertise and training. Thus, Core C will provide critical tools for Program members and, through the development of new imaging approaches, ultimately the broader cancer research community.