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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-GRB-S)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Dana-Farber Cancer Institute
United States
Zip Code
Becker, Jürgen C; Stang, Andreas; Hausen, Axel Zur et al. (2018) Epidemiology, biology and therapy of Merkel cell carcinoma: conclusions from the EU project IMMOMEC. Cancer Immunol Immunother 67:341-351
Becker, Jürgen C; Stang, Andreas; DeCaprio, James A et al. (2017) Merkel cell carcinoma. Nat Rev Dis Primers 3:17077
Denis, Deborah; Rouleau, Cecile; Schaffhausen, Brian S (2017) A Transformation-Defective Polyomavirus Middle T Antigen with a Novel Defect in PI3 Kinase Signaling. J Virol 91:
Starrett, Gabriel J; Marcelus, Christina; Cantalupo, Paul G et al. (2017) Merkel Cell Polyomavirus Exhibits Dominant Control of the Tumor Genome and Transcriptome in Virus-Associated Merkel Cell Carcinoma. MBio 8:
Cizmecioglu, Onur; Ni, Jing; Xie, Shaozhen et al. (2016) Rac1-mediated membrane raft localization of PI3K/p110? is required for its activation by GPCRs or PTEN loss. Elife 5:
Rouleau, Cecile; Pores Fernando, Arun T; Hwang, Justin H et al. (2016) Transformation by Polyomavirus Middle T Antigen Involves a Unique Bimodal Interaction with the Hippo Effector YAP. J Virol 90:7032-7045
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
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
Hettmer, Simone; Schinzel, Anna C; Tchessalova, Daria et al. (2015) Functional genomic screening reveals asparagine dependence as a metabolic vulnerability in sarcoma. Elife 4:
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

Showing the most recent 10 out of 147 publications