The Mouse Pathology and Imaging Core has been an essential part of the Thyroid Cancer P01 grant, supporting the use of mouse models for all four of the research projects. A major goal of the Core will be to provide expertise in mouse pathology with a specific focus on detailed aspects of thyroid gland pathology, including the pathobiology of mouse thyroid carcinoma. Pathology support will be provided by veterinary anatomic and clinical pathologists that are Diplomates of the American College of Veterinary Pathologists. Expertise in comparative thyroid gland pathology will enable appropriate interpretation and evaluation of the mouse models in the research projects and comparison to human thyroid cancer. The mouse clinical pathology service also includes full-service hematology and clinical chemistry analyzers in the laboratory of Dr. Krista La Perie that can appropriately analyze small blood volumes from mice. This structure will provide excellence and continuity of service for the research projects, and allow consistency and high level integration of pathologic changes observed in the various mouse models used in this project. Additionally, this core will provide state-of-the art imaging services with developed expertise in advanced modalities specific for the analysis of the thyroid gland, such as anatomic imaging using high resolution, 3D mouse thyroid ultrasonography and functional imaging using integrated microCT/microSPECT/microPET. This latter imaging is capable of analyzing the same radiotracers in mice as are used clinically in human patients with thyroid cancer, including radioiodide to assess iodide uptake and retention, and fiuorodeoxyglucose to assess metabolic activity. Additional imaging modes available through the core include digital Faxitron high resolution radiography, high resolution small animal magnetic resonance imaging (MRI), and whole animal or organ bioluminescence and fluorescence imaging. Other services that will be available to investigators include (1) technical expertise and support for the primary culture of mouse thyroid tumors;(2) support for studies on metastasis including orthotopic implantation of tumor tissue into the thyroid bed and injection of tumor cells into the tail vein and/or left cardiac ventricle to induce metastatic disease;and (3) support for the development of new transgenic and targeted alleles for novel mouse model development. Facilities will include a necropsy facility, automated immunostainers, microscopy facilities including a multi-headed microscope with video output for conferences, dedicated bioluminescent and fluorescent in vivo imaging instrumentation, dedicated high resolution/high frequency ultrasound equipment for small animals, digital gross and microscopic photography facilities, quantitative image analysis software, and mouse surgery and radiology facilities. Because the science in this project is spread among various models and physical locations, the availability of a single core to coordinate, analyze, and compare data will provide an essential resource and significantly enhance the quality and validity ofthe research data.

Public Health Relevance

As tools for the identification of the molecular events that predispose to the initiation, promotion, and development of thyroid cancer and its metastasis have become more sophisticated, the requirement for physiologic models with which to study these processes has also grown. The Mouse Imaging and Pathology Core provides an integrated resource for the generation and analysis of models used to study these processes in the mouse, which is the most effective and efficient in vivo system for studying human cancer. The availability of a this core supports the overall Program Project goals not only by fostering cutting edge mouse modeling of thyroid cancer, but also by serving as a collaborative focus through which project scientists can interact in elucidating how genetic and non-genetic alterations affect all aspects of thyroid cancer biology in the living organism.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA124570-07
Application #
8697758
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
7
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
DUNS #
City
Columbus
State
OH
Country
United States
Zip Code
Yu, Wanfeng; Ni, Ying; Saji, Motoyasu et al. (2017) Cowden syndrome-associated germline succinate dehydrogenase complex subunit D (SDHD) variants cause PTEN-mediated down-regulation of autophagy in thyroid cancer cells. Hum Mol Genet 26:1365-1375
Gudmundsson, Julius; Thorleifsson, Gudmar; Sigurdsson, Jon K et al. (2017) A genome-wide association study yields five novel thyroid cancer risk loci. Nat Commun 8:14517
Azmat, Umal; Porter, Kyle; Senter, Leigha et al. (2017) Thyroglobulin Liquid Chromatography-Tandem Mass Spectrometry Has a Low Sensitivity for Detecting Structural Disease in Patients with Antithyroglobulin Antibodies. Thyroid 27:74-80
Chen, Hannah H; Händel, Norman; Ngeow, Joanne et al. (2017) Immune dysregulation in patients with PTEN hamartoma tumor syndrome: Analysis of FOXP3 regulatory T cells. J Allergy Clin Immunol 139:607-620.e15
Rossfeld, Kara K; Justiniano, Steven E; Ding, Haiming et al. (2017) Biological Evaluation of a Fluorescent-Imaging Agent for Medullary Thyroid Cancer in an Orthotopic Model. J Clin Endocrinol Metab 102:3268-3277
Saporito, Donika; Brock, Pamela; Hampel, Heather et al. (2017) Penetrance of a rare familial mutation predisposing to papillary thyroid cancer. Fam Cancer :
Byrd, Victoria; Getz, Ted M; Padmanabhan, Roshan et al. (2017) Microbiome in PTEN hamartoma tumor syndrome. Endocr Relat Cancer :
Tomsic, Jerneja; Fultz, Rebecca; Liyanarachchi, Sandya et al. (2017) Variants in microRNA genes in familial papillary thyroid carcinoma. Oncotarget 8:6475-6482
Ni, Ying; Seballos, Spencer; Fletcher, Benjamin et al. (2017) Germline compound heterozygous poly-glutamine deletion in USF3 may be involved in predisposition to heritable and sporadic epithelial thyroid carcinoma. Hum Mol Genet 26:243-257
Ashtekar, Amruta; Huk, Danielle; Magner, Alexa et al. (2017) Sdhd ablation promotes thyroid tumorigenesis by inducing a stem-like phenotype. Endocr Relat Cancer 24:579-591

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