Abstract

We propose experiments in years 21 to 25 of a successful Program to investigate the molecular basis of cell transformation by DNA tumor viruses. The five participating laboratories are organized into two clusters. The papillomavirus cluster will focus on the Human papillomaviruses, which have been strongly implicated in the genesis of common human cancers, particularly cervical cancer. Dr. Brandsma will continue her attempts to optimize papilloma induction with cloned HPV16DNA, a project with the potential to represent a real breakthrough in papillomavirus research. Dr. DiMaio will continue his mechanistic studies on the HPV16 E5 transforming protein. The Herpes virus cluster will focus on Epstein-Barr virus and related viruses associated with lymphoproliferative diseases and other cancers. In related projects, Drs. Miller and Maizels will explore the functions of cellular DNA binding proteins implicated in regulating the viral life cycle and structure of the viral DNA. Dr. Steitz will continue her analysis of the role of small viral-encoded RNAs in transformation and other aspects of host cell metabolism. In addition, a protein expression and purification core will provide essential services to the Program. This Program represents the significant commitment of the Yale University School of Medicine and the participating investigators to studies that may well have direct relevance to understanding the cause of human cancer.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA016038-24
Application #
2414071
Study Section
Special Emphasis Panel (SRC (24))
Project Start
1979-05-01
Project End
1999-04-30
Budget Start
1997-05-01
Budget End
1998-04-30
Support Year
24
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Yale University
Department
Genetics
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Zhang, Pengwei; Monteiro da Silva, Gabriel; Deatherage, Catherine et al. (2018) Cell-Penetrating Peptide Mediates Intracellular Membrane Passage of Human Papillomavirus L2 Protein to Trigger Retrograde Trafficking. Cell 174:1465-1476.e13
Inoue, Takamasa; Zhang, Pengwei; Zhang, Wei et al. (2018) ?-Secretase promotes membrane insertion of the human papillomavirus L2 capsid protein during virus infection. J Cell Biol 217:3545-3559
Vallery, Tenaya K; Withers, Johanna B; Andoh, Joana A et al. (2018) Kaposi's Sarcoma-Associated Herpesvirus mRNA Accumulation in Nuclear Foci Is Influenced by Viral DNA Replication and Viral Noncoding Polyadenylated Nuclear RNA. J Virol 92:
Hayes, Karen E; Barr, Jamie A; Xie, Mingyi et al. (2018) Immunoprecipitation of Tri-methylated Capped RNA. Bio Protoc 8:
Park, Richard; Miller, George (2018) Epstein-Barr Virus-Induced Nodules on Viral Replication Compartments Contain RNA Processing Proteins and a Viral Long Noncoding RNA. J Virol 92:
Singh, Gatikrushna; Fritz, Sarah M; Ranji, Arnaz et al. (2017) Isolation of Cognate RNA-protein Complexes from Cells Using Oligonucleotide-directed Elution. J Vis Exp :
Martinez, Ivan; Hayes, Karen E; Barr, Jamie A et al. (2017) An Exportin-1-dependent microRNA biogenesis pathway during human cell quiescence. Proc Natl Acad Sci U S A 114:E4961-E4970
Lipovsky, Alex; Erden, Asu; Kanaya, Eriko et al. (2017) The cellular endosomal protein stannin inhibits intracellular trafficking of human papillomavirus during virus entry. J Gen Virol 98:2821-2836
Lee, Nara; Yario, Therese A; Gao, Jessica S et al. (2016) EBV noncoding RNA EBER2 interacts with host RNA-binding proteins to regulate viral gene expression. Proc Natl Acad Sci U S A 113:3221-6
DiMaio, Daniel (2016) Thank You, Edward. Merci, Louis. PLoS Pathog 12:e1005320

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