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

Furuse, Yuki, Ryan Finethy, Hector A. Saka, Ana M. Xet-Mull, Dana M. Sisk, Kristen L Jurcic Smith, Sunhee Lee, et al. “Search for microRNAs expressed by intracellular bacterial pathogens in infected mammalian cells..” Plos One 9, no. 9 (2014). https://doi.org/10.1371/journal.pone.0106434.

PMID
25184567
Full Text

Furuse, Yuki, David A. Ornelles, and Bryan R. Cullen. “Persistently adenovirus-infected lymphoid cells express microRNAs derived from the viral VAI and especially VAII RNA..” Virology 447, no. 1–2 (December 2013): 140–45. https://doi.org/10.1016/j.virol.2013.08.024.

PMID
24210108
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Cullen, Bryan R., Sara Cherry, and Benjamin R. tenOever. “Is RNA interference a physiologically relevant innate antiviral immune response in mammals?.” Cell Host Microbe 14, no. 4 (October 16, 2013): 374–78. https://doi.org/10.1016/j.chom.2013.09.011.

PMID
24139396
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Jin, Hyun Yong, Hiroyo Oda, Maoyi Lai, Rebecca L. Skalsky, Kelly Bethel, Jovan Shepherd, Seung Goo Kang, et al. “MicroRNA-17~92 plays a causative role in lymphomagenesis by coordinating multiple oncogenic pathways..” Embo J 32, no. 17 (August 28, 2013): 2377–91. https://doi.org/10.1038/emboj.2013.178.

PMID
23921550
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Majoros, William H., Parawee Lekprasert, Neelanjan Mukherjee, Rebecca L. Skalsky, David L. Corcoran, Bryan R. Cullen, and Uwe Ohler. “MicroRNA target site identification by integrating sequence and binding information..” Nat Methods 10, no. 7 (July 2013): 630–33. https://doi.org/10.1038/nmeth.2489.

PMID
23708386
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Flores, Omar, Sanae Nakayama, Adam W. Whisnant, Hassan Javanbakht, Bryan R. Cullen, and David C. Bloom. “Mutational inactivation of herpes simplex virus 1 microRNAs identifies viral mRNA targets and reveals phenotypic effects in culture..” J Virol 87, no. 12 (June 2013): 6589–6603. https://doi.org/10.1128/JVI.00504-13.

PMID
23536669
Full Text

Majoros, W. H., P. Lekprasert, N. Mukherjee, R. L. Skalsky, D. L. Corcoran, B. R. Cullen, and U. Ohler. “MicroRNA target site identification by integrating sequence and binding information.” Nature Methods, May 26, 2013. https://doi.org/10.138/nmeth.2489.

Full Text

Wahl, Angela, Sarah D. Linnstaedt, Caitlin Esoda, John F. Krisko, Francisco Martinez-Torres, Henri-Jacques Delecluse, Bryan R. Cullen, and J Victor Garcia. “A cluster of virus-encoded microRNAs accelerates acute systemic Epstein-Barr virus infection but does not significantly enhance virus-induced oncogenesis in vivo..” J Virol 87, no. 10 (May 2013): 5437–46. https://doi.org/10.1128/JVI.00281-13.

PMID
23468485
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Whisnant, Adam W., Hal P. Bogerd, Omar Flores, Phong Ho, Jason G. Powers, Natalia Sharova, Mario Stevenson, Chin-Ho Chen, and Bryan R. Cullen. “In-depth analysis of the interaction of HIV-1 with cellular microRNA biogenesis and effector mechanisms..” Mbio 4, no. 2 (April 16, 2013). https://doi.org/10.1128/mBio.00193-13.

PMID
23592263
Full Text

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