The Program applies a combination of biochemistry, cell biology, genetics and mouse models of human cancer with a unified goal of revealing key tumorigenic pathways. The success of targeted therapeutics continues to reinforce the view that understanding the biology of the cancer cell is the key to treating this disease. Throughout its 35 year history, this Program has focused on translating lessons from DNA tumor viruses into an understanding of both normal cellular and tumor biology. This remains a focus of the Program;however, as the view has shifted from viral to cellular proteins, so is the emphasis evolving from the cancer cell to a broader consideration of the tumor as a tissue. This Program is composed of six highly integrated and mutually supporting Projects and four Cores. The Program is unified buy several themes which run throughout its components. First is the conviction that DNA tumor viruses have been driven by evolution to target the minimal set of fundamental cellular networks that hold the keys to tumorigenic growth. By moving downstream from the viral proteins themselves to their closest cellular counterparts, may projects within the program strive to understand how alterations in c-Myc promote transformation in different cellular and tissue contexts. The Program is also unified in the study of a new class of RNA regulatory molecules, the microRNAs, that act as oncogenes. The Program also exploits these as experimental tools to study gene function. Finally, the Program is cast in the context of sophisticated cancer models that use engineered stem and progenitor cells to rapidly reconstitute organ systems with nearly any desired genetic alteration. The findings from this Program have the potential both to inform the effective application of current therapies and to identify proteins and networks that may become targets for the development of new therapeutic agents.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Study Section
Special Emphasis Panel (ZCA1-GRB-S (O1))
Program Officer
Spalholz, Barbara A
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Cold Spring Harbor Laboratory
Cold Spring Harbor
United States
Zip Code
Diermeier, Sarah D; Chang, Kung-Chi; Freier, Susan M et al. (2016) Mammary Tumor-Associated RNAs Impact Tumor Cell Proliferation, Invasion, and Migration. Cell Rep 17:261-74
O'Rourke, Kevin P; Dow, Lukas E; Lowe, Scott W (2016) Immunofluorescent Staining of Mouse Intestinal Stem Cells. Bio Protoc 6:
Anczuków, Olga; Krainer, Adrian R (2016) Splicing-factor alterations in cancers. RNA 22:1285-301
Tschaharganeh, Darjus F; Lowe, Scott W; Garippa, Ralph J et al. (2016) Using CRISPR/Cas to study gene function and model disease in vivo. FEBS J 283:3194-203
Hossain, Manzar; Stillman, Bruce (2016) Opposing roles for DNA replication initiator proteins ORC1 and CDC6 in control of Cyclin E gene transcription. Elife 5:
Arun, Gayatri; Diermeier, Sarah; Akerman, Martin et al. (2016) Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss. Genes Dev 30:34-51
Tschaharganeh, Darjus F; Xue, Wen; Calvisi, Diego F et al. (2016) p53-Dependent Nestin Regulation Links Tumor Suppression to Cellular Plasticity in Liver Cancer. Cell 165:1546-1547
O'Rourke, Kevin P; Ackerman, Sarah; Dow, Lukas E et al. (2016) Isolation, Culture, and Maintenance of Mouse Intestinal Stem Cells. Bio Protoc 6:
Tschaharganeh, Darjus F; Bosbach, Benedikt; Lowe, Scott W (2016) Coordinated Tumor Suppression by Chromosome 8p. Cancer Cell 29:617-9
Guo, Ya; Xu, Quan; Canzio, Daniele et al. (2015) CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function. Cell 162:900-10

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