The construction and phenotypic analysis of genetically engineered mouse (GEM) strains are fundamental and integral for the study of pancreatic cancer, including the analysis of signaling molecules in this pathology, the discovery and analysis of novel genes and their linked networks, and the validation and assessment of novel therapeutic targets and associated molecular biomarkers. The Genetic Engineering Mouse Core (GEMC) of this PDAC POI will provide all the necessary expertise, reagents and services to generate four genetically engineered mouse (GEM) modeling projects per year of grant funding. The GEMC will work closely with POI project leaders, investigators to produce the most advanced cancer relevant GEM strains. Specifically: (A) Transgenics;the GEMC will support all aspects of the construction of transgenic mouse models, including advice, service, technologies and reagents for the optimal design and construction of each specific transgene. (B) Gene Targeting;We will support all aspects of the construction of knockout and knock-in mouse alleles, including provide services, support, advice, technologies and reagents for the optimal design, construction and production of each specific targeting vector and resulting mice. (C) Evaluate and implement new technologies for the construction of genetically engineered mice and derivative cells.

Public Health Relevance

The laboratory mouse has been a central player in aging research. Particularly over the past two decades, numerous laboratories have used the techniques of transgenesis and gene targeting to create novel mouse strains to study pancreatic cancer. The analysis of these strains has led to an improved understanding of the genes involved cancer, cancer related pathological progression, and many other aspects of the oncogenic process that can only be studied in the context of the whole animal. With more genes, more powerful methods of genetic manipulation and greater insight into cancer biology on the molecular and cellular level, the goal to create genetically accurate models of cancer relevant pathologies and processes in the mouse is being realized.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA117969-08
Application #
8507164
Study Section
Special Emphasis Panel (ZCA1-RPRB-0)
Project Start
Project End
Budget Start
2013-01-01
Budget End
2013-12-31
Support Year
8
Fiscal Year
2013
Total Cost
$165,775
Indirect Cost
$13,900
Name
University of Texas MD Anderson Cancer Center
Department
Type
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
Kapoor, Avnish; Yao, Wantong; Ying, Haoqiang et al. (2014) Yap1 activation enables bypass of oncogenic Kras addiction in pancreatic cancer. Cell 158:185-97
Sahora, Klaus; Fernández-del Castillo, Carlos; Dong, Fei et al. (2014) Not all mixed-type intraductal papillary mucinous neoplasms behave like main-duct lesions: implications of minimal involvement of the main pancreatic duct. Surgery 156:611-21
Mayers, Jared R; Wu, Chen; Clish, Clary B et al. (2014) Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. Nat Med 20:1193-8
Lee, John J; Perera, Rushika M; Wang, Huaijun et al. (2014) Stromal response to Hedgehog signaling restrains pancreatic cancer progression. Proc Natl Acad Sci U S A 111:E3091-100
Deschênes-Simard, Xavier; Lessard, Frédéric; Gaumont-Leclerc, Marie-France et al. (2014) Cellular senescence and protein degradation: breaking down cancer. Cell Cycle 13:1840-58
Daver, Naval; Shastri, Aditi; Kadia, Tapan et al. (2014) Phase II study of pomalidomide in combination with prednisone in patients with myelofibrosis and significant anemia. Leuk Res 38:1126-9
Viale, Andrea; Pettazzoni, Piergiorgio; Lyssiotis, Costas A et al. (2014) Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature 514:628-32
Lyssiotis, Costas A; Cantley, Lewis C (2014) Targeting metabolic scavenging in pancreatic cancer. Clin Cancer Res 20:6-8
Commisso, Cosimo; Davidson, Shawn M; Soydaner-Azeloglu, Rengin G et al. (2013) Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature 497:633-7
Lyssiotis, Costas A; Son, Jaekyoung; Cantley, Lewis C et al. (2013) Pancreatic cancers rely on a novel glutamine metabolism pathway to maintain redox balance. Cell Cycle 12:1987-8

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