Bryan R. Cullen, PhD

Professor of Molecular Genetics and Microbiology
James B. Duke Professor of Molecular Genetics and Microbiology
Director, Center for Virology
Professor in Medicine
Member of the Duke Cancer Institute
Campus mail 0424 Clin & Res Labs, Durham, NC 27710
Phone (919) 684-3369
Email address bryan.cullen@duke.edu

My laboratory has for sometime been interested in understanding the molecular biology of the replication cycle of the pathogenic retrovirus HIV-1. Because HIV-1 gene expression is primarily regulated by specific RNA:protein interactions, my laboratory has also become interested in the more general area of RNA sequence mediated gene regulation, including nuclear mRNA export and the phenomenon of RNA interference.

In the past, my laboratory has worked extensively on Tat, the transcriptional regulator encoded by HIV-1, and on Rev, a virally encoded nuclear mRNA export factor. Our major focus at present is a third HIV-1 regulatory protein termed Vif. In the absence of Vif, HIV-1 virions are produced normally but are largely non-infectious. It has now been demonstrated that Vif functions to block an innate human antiretroviral defense pathway that relies on a factor called APOBEC3G or CEM15. In the absence of Vif, APOBEC3G is packaged into virions and induces degradation of the HIV-1 genome during reverse transcription in target cells. Vif directly interacts with APOBEC3G and thereby allows reverse transcription to proceed unimpeded. Among other issues, we are currently interested in how APOBEC3G is packaged into virions and in how Vif blocks APOBEC3G function. The role of APOBEC3G in cellular defense against other retroviruses and retrotransposons is also an area of interest.

A second major research area in my group relates to how microRNA precursors are processed to yield mature microRNAs and how microRNAs, and the closely related small interfering RNAs, function in human cells. We were the first group to demonstrate overexpression of human microRNAs and therefore have a system in place which should allow us to make rapid progress in this area. We also remain interested in using RNA interference to determine the role of specific cellular factors in different processes, including HIV-1 replication and nuclear mRNA export.

Education and Training

  • Ph.D., University of Medicine and Dentistry of New Jersey, 1984

Publications

Gottwein, Eva, David L. Corcoran, Neelanjan Mukherjee, Rebecca L. Skalsky, Markus Hafner, Jeffrey D. Nusbaum, Priscilla Shamulailatpam, et al. “Viral microRNA targetome of KSHV-infected primary effusion lymphoma cell lines..” Cell Host Microbe 10, no. 5 (November 17, 2011): 515–26. https://doi.org/10.1016/j.chom.2011.09.012.

PMID
22100165
Full Text

Feederle, Regina, Janina Haar, Katharina Bernhardt, Sarah D. Linnstaedt, Helmut Bannert, Helge Lips, Bryan R. Cullen, and Henri-Jacques Delecluse. “The members of an Epstein-Barr virus microRNA cluster cooperate to transform B lymphocytes..” J Virol 85, no. 19 (October 2011): 9801–10. https://doi.org/10.1128/JVI.05100-11.

PMID
21752900
Full Text

Bogerd, Hal P., Fengwen Zhang, Paul D. Bieniasz, and Bryan R. Cullen. “Human APOBEC3 proteins can inhibit xenotropic murine leukemia virus-related virus infectivity..” Virology 410, no. 1 (February 5, 2011): 234–39. https://doi.org/10.1016/j.virol.2010.11.011.

PMID
21131013
Full Text

Feederle, Regina, Sarah D. Linnstaedt, Helmut Bannert, Helge Lips, Maja Bencun, Bryan R. Cullen, and Henri-Jacques Delecluse. “A viral microRNA cluster strongly potentiates the transforming properties of a human herpesvirus..” Plos Pathog 7, no. 2 (February 2011). https://doi.org/10.1371/journal.ppat.1001294.

PMID
21379335
Full Text

Linnstaedt, Sarah D., Eva Gottwein, Rebecca L. Skalsky, Micah A. Luftig, and Bryan R. Cullen. “Virally induced cellular microRNA miR-155 plays a key role in B-cell immortalization by Epstein-Barr virus..” J Virol 84, no. 22 (November 2010): 11670–78. https://doi.org/10.1128/JVI.01248-10.

PMID
20844043
Full Text

Umbach, Jennifer L., Lisa I. Strelow, Scott W. Wong, and Bryan R. Cullen. “Analysis of rhesus rhadinovirus microRNAs expressed in virus-induced tumors from infected rhesus macaques..” Virology 405, no. 2 (September 30, 2010): 592–99. https://doi.org/10.1016/j.virol.2010.06.036.

PMID
20655562
Full Text

Umbach, Jennifer L., Hui-Ling Yen, Leo L. M. Poon, and Bryan R. Cullen. “Influenza A virus expresses high levels of an unusual class of small viral leader RNAs in infected cells..” Mbio 1, no. 4 (September 14, 2010). https://doi.org/10.1128/mBio.00204-10.

PMID
20842206
Full Text

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