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.
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.
|Lundquist, Mark R; Goncalves, Marcus D; Loughran, Ryan M et al. (2018) Phosphatidylinositol-5-Phosphate 4-Kinases Regulate Cellular Lipid Metabolism By Facilitating Autophagy. Mol Cell 70:531-544.e9|
|Hopkins, Benjamin D; Pauli, Chantal; Du, Xing et al. (2018) Suppression of insulin feedback enhances the efficacy of PI3K inhibitors. Nature 560:499-503|
|Biancur, Douglas E; Kimmelman, Alec C (2018) The plasticity of pancreatic cancer metabolism in tumor progression and therapeutic resistance. Biochim Biophys Acta Rev Cancer 1870:67-75|
|Chen, Yang; LeBleu, Valerie S; Carstens, Julienne L et al. (2018) Dual reporter genetic mouse models of pancreatic cancer identify an epithelial-to-mesenchymal transition-independent metastasis program. EMBO Mol Med 10:|
|Hill, Margaret A; Alexander, William B; Guo, Bing et al. (2018) Kras and Tp53 Mutations Cause Cholangiocyte- and Hepatocyte-Derived Cholangiocarcinoma. Cancer Res 78:4445-4451|
|Mendt, Mayela; Kamerkar, Sushrut; Sugimoto, Hikaru et al. (2018) Generation and testing of clinical-grade exosomes for pancreatic cancer. JCI Insight 3:|
|Patra, Krushna C; Kato, Yasutaka; Mizukami, Yusuke et al. (2018) Mutant GNAS drives pancreatic tumourigenesis by inducing PKA-mediated SIK suppression and reprogramming lipid metabolism. Nat Cell Biol 20:811-822|
|Anglin, Justin; Zavareh, Reza Beheshti; Sander, Philipp N et al. (2018) Discovery and optimization of aspartate aminotransferase 1 inhibitors to target redox balance in pancreatic ductal adenocarcinoma. Bioorg Med Chem Lett 28:2675-2678|
|Yang, Annan; Herter-Sprie, Grit; Zhang, Haikuo et al. (2018) Autophagy Sustains Pancreatic Cancer Growth through Both Cell-Autonomous and Nonautonomous Mechanisms. Cancer Discov 8:276-287|
|Santana-Codina, Naiara; Roeth, Anjali A; Zhang, Yi et al. (2018) Oncogenic KRAS supports pancreatic cancer through regulation of nucleotide synthesis. Nat Commun 9:4945|
Showing the most recent 10 out of 134 publications