The ability to manipulate gene expression is a fundamental tool essential for molecular studies. In model organisms, methods and tools to delete or overexpress genes have provided the means to study and characterize the molecular basis of complex biological phenomenon. Recent advances in genome biology and the discovery that RNA interference operates in mammalian cells now provide a foundation for similar studies in mammalian cells. Indeed, nearly every molecular biologically based project now requires the use of RNAi and expression clones. Over the past several years, investigators in this P01 have developed comprehensive tools to manipulate gene expression in mammalian cells. In addition, we have developed a facility that has the equipment and expertise to perform high throughput RNAi and expression screens. Based on these advances, we have created a gene function manipulation core to support the projects in this P01. Specifically, this core will provide lentivirally delivered short hairpin RNA (shRNA) reagents and cDNA clones to program investigators. In addition, this facility will work with P01 investigators to perform shRNA and overexpression screens to elucidate components of the pathways perturbed by viral oncoproteins. Although such reagents can be developed on a gene-by-gene basis, this core facility will provide the reagents and means to manipulate gene expression in a comprehensive manner that is both efficient and cost effective. The access and use of this facility will thus accelerate progress for each of the projects that comprise this program.

Public Health Relevance

Although only rare human cancers derive from a viral etiology, the study of DNA tumor viruses that transform rodent and human cells has led to a greater understanding of the molecular events that program the malignant state in all human cancers. To enhance the^bility of program investigators to decipher these cancer-essential pathways, this core facility will provide reagents, equipment and expertise that will not only accelerate discovery but also provide the means to perform comprehensive evaluations of specific biological phenomena.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA050661-25
Application #
8448554
Study Section
Special Emphasis Panel (ZCA1-GRB-S)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
25
Fiscal Year
2013
Total Cost
$192,603
Indirect Cost
$58,986
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
02215
Cizmecioglu, Onur; Ni, Jing; Xie, Shaozhen et al. (2016) Rac1-mediated membrane raft localization of PI3K/p110β is required for its activation by GPCRs or PTEN loss. Elife 5:
Galligan, Jeffrey T; Martinez-Noël, Gustavo; Arndt, Verena et al. (2015) Proteomic analysis and identification of cellular interactors of the giant ubiquitin ligase HERC2. J Proteome Res 14:953-66
Howley, Peter M; Pfister, Herbert J (2015) Beta genus papillomaviruses and skin cancer. Virology 479-480:290-6
Hettmer, Simone; Schinzel, Anna C; Tchessalova, Daria et al. (2015) Functional genomic screening reveals asparagine dependence as a metabolic vulnerability in sarcoma. Elife 4:
Berrios, Christian; Jung, Joonil; Primi, Blake et al. (2015) Malawi polyomavirus is a prevalent human virus that interacts with known tumor suppressors. J Virol 89:857-62
Spurgeon, Megan E; Cheng, Jingwei; Bronson, Roderick T et al. (2015) Tumorigenic activity of merkel cell polyomavirus T antigens expressed in the stratified epithelium of mice. Cancer Res 75:1068-79
Pores Fernando, A T; Andrabi, S; Cizmecioglu, O et al. (2015) Polyoma small T antigen triggers cell death via mitotic catastrophe. Oncogene 34:2483-92
White, Elizabeth A; Kramer, Rebecca E; Hwang, Justin H et al. (2015) Papillomavirus E7 oncoproteins share functions with polyomavirus small T antigens. J Virol 89:2857-65
Luo, Leo Y; Kim, Eejung; Cheung, Hiu Wing et al. (2015) The Tyrosine Kinase Adaptor Protein FRS2 Is Oncogenic and Amplified in High-Grade Serous Ovarian Cancer. Mol Cancer Res 13:502-9
White, Elizabeth A; Walther, Johanna; Javanbakht, Hassan et al. (2014) Genus beta human papillomavirus E6 proteins vary in their effects on the transactivation of p53 target genes. J Virol 88:8201-12

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