This program-project has two interdependent themes. To use molecular biology and genetics both to elucidate the life cycles of human tumor viruses and to characterize the mechanisms by which these tumor viruses transform infected cells. Lambert studies papillomaviruses; Loeb studies hepatitis B viruses; Mertz studies papova and hepatitis B viruses; Panganiban studies retroviruses; and Sugden studies human herpesviruses. These investigators use parallel approaches to study most known human tumor viruses. Their shared intellectual and experimental commitments support advances in one family of tumor viruses being applied to another. Loeb and Panganiban work on viruses-duck, heron, and human hepatitis B viruses and human immunodeficiency virus, which use reverse transcription in their life cycles. They are characterizing the synthesis of the viral genomes, genome structure, and virion maturations. Mertz works on the mechanism of export from the nucleus of viral RNAs, a problem of clear interest to Panganiban. Mertz also is defining one means by which cellular proteins regulate simian virus 40 late gene expression, a wide-ranging problem of interest central both to Lambert and Sugden. Lambert is defining the mechanisms by which human papilloma viral oncogenes affect host cell physiology. He is also dissecting the mechanisms by which human papilloma viral oncogenes affect host cell physiology. He is also dissecting the regulation and replication of papillomaviral plasmids in parallel with Sugden's research on the replication of Epstein-Barr viral plasmids. Sugden studies too an Epstein-Barr viral oncogene in order to reveal its effects on host cell physiology. All of this research has as its goal understanding viral carcinogenesis both by tractable viruses and by the viruses that cause cancer in people. All of these studies will provide new understandings of how tumor viruses propagate and act as carcinogens.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA022443-23
Application #
6172557
Study Section
Subcommittee G - Education (NCI)
Program Officer
Daschner, Phillip J
Project Start
1993-04-16
Project End
2003-04-30
Budget Start
2000-05-01
Budget End
2001-04-30
Support Year
23
Fiscal Year
2000
Total Cost
$1,356,692
Indirect Cost
Name
University of Wisconsin Madison
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Chiu, Ya-Fang; Sugden, Bill (2018) Plasmid Partitioning by Human Tumor Viruses. J Virol 92:
Shin, Myeong-Kyun; Payne, Susan N; Bilger, Andrea et al. (2018) Activating Mutations in Pik3caContribute to Anal Carcinogenesis in the Presence or Absence of HPV-16 Oncogenes. Clin Cancer Res :
Hoebe, Eveline; Wille, Coral; Hagemeier, Stacy et al. (2018) Epstein-Barr Virus Gene BARF1 Expression is Regulated by the Epithelial Differentiation Factor ?Np63? in Undifferentiated Nasopharyngeal Carcinoma. Cancers (Basel) 10:
Nyman, Patrick E; Buehler, Darya; Lambert, Paul F (2018) Loss of Function of Canonical Notch Signaling Drives Head and Neck Carcinogenesis. Clin Cancer Res 24:6308-6318
Weng, Chao; Lee, Denis; Gelbmann, Christopher B et al. (2018) Human Cytomegalovirus Productively Replicates In Vitro in Undifferentiated Oral Epithelial Cells. J Virol 92:
Bristol, Jillian A; Djavadian, Reza; Albright, Emily R et al. (2018) A cancer-associated Epstein-Barr virus BZLF1 promoter variant enhances lytic infection. PLoS Pathog 14:e1007179
Romero-Masters, James C; Ohashi, Makoto; Djavadian, Reza et al. (2018) An EBNA3C-deleted Epstein-Barr virus (EBV) mutant causes B-cell lymphomas with delayed onset in a cord blood-humanized mouse model. PLoS Pathog 14:e1007221
UmaƱa, Angie C; Iwahori, Satoko; Kalejta, Robert F (2018) Direct Substrate Identification with an Analog Sensitive (AS) Viral Cyclin-Dependent Kinase (v-Cdk). ACS Chem Biol 13:189-199
Meyers, Jordan M; Grace, Miranda; Uberoi, Aayushi et al. (2018) Inhibition of TGF-? and NOTCH Signaling by Cutaneous Papillomaviruses. Front Microbiol 9:389
Uberoi, Aayushi; Yoshida, Satoshi; Lambert, Paul F (2018) Development of an in vivo infection model to study Mouse papillomavirus-1 (MmuPV1). J Virol Methods 253:11-17

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