The University of California (UC), Davis Center for Translational Genomic Phenotyping (CTGP): A National Cancer Institute-Mouse Models of Human Cancer Consortium (NCI-MMHCC) Science Leadership Application will provide centralized discovery-driven in-vivo and ex-vivo phenotyping for validation of model pathology. This is predominantly centered on Cancer Biology, but Impacts Preventative Interventions, Experimental Therapeutics and Cancer Susceptibility programs as well. The application is organized in five sections. 1. As a Summary of the Research, the PI, Dr. Robert Cardiff, is a Co-Pl, Co-I and collaborator on several past and newly submitted MMHCC research projects. He Is Co-l on "Goal 1" research applications submitted with Lewis Chodosh, Cory Abate-Shen, and Robert Schreiber. He has consistently provided consultation and leadership within the MMHCC Consortium with respect to phenotypes, translation of pathologic findings in the mouse to the human disease, and defining and publicizing criteria for diagnosis, staging and grading critical to the use of the mouse models in cancer biology, prevention, and experimental therapeutics. 2. The Leadership Plan will A) electronically coordinate intra-NCI-MMHCC projects in the specific research clusters of Preventative Interventions and Cancer Biology and anticipate fostering collaborations among the U0l awardees who are affiliated with these research clusters;B) foster collaborations throughout the MMHCC and with other NCI networks and consortia to delineate research resources or pilot projects that promote the cluster collaborations;and C) manage and enhance the existing NCI cancer model bioinformatics infrastructure through caELMIR with Integrated image archives of in-vivo and ex-vivo images that are accurately mapped to relevant human bioinformatics systems in collaboration. 3. The Communication and Coordination will be achieved through the informatics tools connecting the MMHCC research affiliates with the expert pathology/phenotyping resource embodied In the Academy for Genomic Pathology. This group constitutes most of the leading authorities and most experienced mouse model and comparative pathologists in the country. 4. Outreach will be achieved through symposia and workshops, as well as an open visiting trainee/ visiting professor program at the UC Davis center. In addition, the connections at UC Davis to the Mutant Mouse Regional Resource Center, and the Knockout Mouse Project Repository provide added outreach to the mouse modeling community. 5. Pre-Clinical Models Informatics for the MMHCC and the NCI has been developed, in part, by our group at UC Davis. Studies have been Initiated at UC Davis, and specific pilot projects designs demanding accurate integrated data from mouse colony management, pathology laboratory information systems, whole slide images, radiology image data and display and electronic "lab notebooks" using caELMIR, caMOD, and the caBIG infrastructure. This application is uniquely relevant to the program priorities. This is a Leadership U01 centered on phenotyping and pathology, with extensive support from a host of national experts In mouse pathology, and extensive background and preliminary work In development of Informatics uniquely designed to the purposes of the MMHCC consortium

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA141582-04
Application #
8327686
Study Section
Special Emphasis Panel (ZCA1-SRLB-Q (M1))
Program Officer
Marks, Cheryl L
Project Start
2009-09-01
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
4
Fiscal Year
2012
Total Cost
$671,809
Indirect Cost
$266,306
Name
University of California Davis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Engelberg, Jesse A; Giberson, Richard T; Young, Lawrence J T et al. (2014) The use of mouse models of breast cancer and quantitative image analysis to evaluate hormone receptor antigenicity after microwave-assisted formalin fixation. J Histochem Cytochem 62:319-34
Cardiff, Robert D; Borowsky, Alexander D (2014) At last: classification of human mammary cells elucidates breast cancer origins. J Clin Invest 124:478-80
Cardiff, Robert D; Miller, Claramae H; Munn, Robert J (2014) Analysis of mouse model pathology: a primer for studying the anatomic pathology of genetically engineered mice. Cold Spring Harb Protoc 2014:561-80
Cardiff, Robert D; Hubbard, Neil E; Engelberg, Jesse A et al. (2013) Quantitation of fixative-induced morphologic and antigenic variation in mouse and human breast cancers. Lab Invest 93:480-97
Ittmann, Michael; Huang, Jiaoti; Radaelli, Enrico et al. (2013) Animal models of human prostate cancer: the consensus report of the New York meeting of the Mouse Models of Human Cancers Consortium Prostate Pathology Committee. Cancer Res 73:2718-36
Couto, S S; Bolon, B; Cardiff, R D (2012) Morphologic manifestations of gene-specific molecular alterations ("genetic addictions") in mouse models of disease. Vet Pathol 49:116-29
Leung, J Y; Andrechek, E R; Cardiff, R D et al. (2012) Heterogeneity in MYC-induced mammary tumors contributes to escape from oncogene dependence. Oncogene 31:2545-54
Cardiff, Robert D; Borowsky, Alexander D (2010) Precancer: sequentially acquired or predetermined? Toxicol Pathol 38:171-9
Damonte, Patrizia; Gregg, Jeffrey P; Borowsky, Alexander D et al. (2007) EMT tumorigenesis in the mouse mammary gland. Lab Invest 87:1218-26