The scientific goals and central themes of the Mouse Models and Cancer Stem Cells Program are to investigate different aspects of stem cell function, including self renewal, reprogramming, and dedifferentiation and differentiation, using mouse, Drosophila, Xenopus, and zebrafish as models, with the goal of learning more about embryonic, tissue and cancer stem cells. Linked to this are major efforts to use induced pluripotent stem cell (iPSC) technology to study mechanisms of genomic reprogramming, including changes in DNA methylation patterns, to learn how cancer stem cells might arise through genomic reprogramming, and to develop disease-in-a dish models of human diseases. Developmental signaling pathways that are often reactivated and used to drive cancer cell phenotypes are being studied, including the Wnt/p-catenin pathway, the ERBB2, RET, and TAM receptor tyrosine kinases, and TGF-p pathways. The development and use of mouse models to study cancer biology and the role of inflammation in carcinogenesis are also important goals, and also to utilize lentivirus vectors for cancer therapy and for development of new cancer models. The program includes twelve members from eight different Laboratories (Departments), see the following page for a list of personnel. The NCI and other peer-reviewed cancer related support (direct costs) for the last budget year was $10,760,318. The substantial NIH and other federal support for this program is outlined in the table of externally funded research projects. The total number of cancer-relevant publications by members of this program in the last grant period (2008- 2012) was 237. Of the total publications, 7% were intraprogrammatic and 12% were interprogrammatic.

Public Health Relevance

The study of human cancer requires the development of animal models that recapitulate human disease. This program will focus on development of mouse models and stem cell approaches to studying cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA014195-43
Application #
8984277
Study Section
Subcommittee I - Transistion to Independence (NCI)
Project Start
Project End
Budget Start
2015-12-01
Budget End
2016-11-30
Support Year
43
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
078731668
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Lewis Jr, Tommy L; Kwon, Seok-Kyu; Lee, Annie et al. (2018) MFF-dependent mitochondrial fission regulates presynaptic release and axon branching by limiting axonal mitochondria size. Nat Commun 9:5008
Eichner, Lillian J; Brun, Sonja N; Herzig, Sébastien et al. (2018) Genetic Analysis Reveals AMPK Is Required to Support Tumor Growth in Murine Kras-Dependent Lung Cancer Models. Cell Metab :
Dravis, Christopher; Chung, Chi-Yeh; Lytle, Nikki K et al. (2018) Epigenetic and Transcriptomic Profiling of Mammary Gland Development and Tumor Models Disclose Regulators of Cell State Plasticity. Cancer Cell 34:466-482.e6
Zarrinpar, Amir; Chaix, Amandine; Xu, Zhenjiang Z et al. (2018) Antibiotic-induced microbiome depletion alters metabolic homeostasis by affecting gut signaling and colonic metabolism. Nat Commun 9:2872
Ramaswamy, Suvasini; Tonnu, Nina; Menon, Tushar et al. (2018) Autologous and Heterologous Cell Therapy for Hemophilia B toward Functional Restoration of Factor IX. Cell Rep 23:1565-1580
Hsu, Cynthia L; Lee, Elian X; Gordon, Kara L et al. (2018) MAP4K3 mediates amino acid-dependent regulation of autophagy via phosphorylation of TFEB. Nat Commun 9:942
Sonntag, Tim; Vaughan, Joan M; Montminy, Marc (2018) 14-3-3 proteins mediate inhibitory effects of cAMP on salt-inducible kinases (SIKs). FEBS J 285:467-480
Herzig, Sébastien; Shaw, Reuben J (2018) AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol 19:121-135
Sweeney, Lora B; Bikoff, Jay B; Gabitto, Mariano I et al. (2018) Origin and Segmental Diversity of Spinal Inhibitory Interneurons. Neuron 97:341-355.e3
Hartmann, Phillipp; Hochrath, Katrin; Horvath, Angela et al. (2018) Modulation of the intestinal bile acid/farnesoid X receptor/fibroblast growth factor 15 axis improves alcoholic liver disease in mice. Hepatology 67:2150-2166

Showing the most recent 10 out of 457 publications