Bryan R. Cullen, PhD

Professor of Molecular Genetics and Microbiology
James B. Duke Distinguished 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

Bogerd, Hal P., Rebecca L. Skalsky, Edward M. Kennedy, Yuki Furuse, Adam W. Whisnant, Omar Flores, Kimberly L. W. Schultz, et al. “Replication of many human viruses is refractory to inhibition by endogenous cellular microRNAs..” J Virol 88, no. 14 (July 2014): 8065–76. https://doi.org/10.1128/JVI.00985-14.

PMID
24807715
Full Text

Skalsky, Rebecca L., Ken E. Olson, Carol D. Blair, Mariano A. Garcia-Blanco, and Bryan R. Cullen. “A "microRNA-like" small RNA expressed by Dengue virus?.” Proc Natl Acad Sci U S A 111, no. 23 (June 10, 2014). https://doi.org/10.1073/pnas.1406854111.

PMID
24853506
Full Text

Bogerd, Hal P., Adam W. Whisnant, Edward M. Kennedy, Omar Flores, and Bryan R. Cullen. “Derivation and characterization of Dicer- and microRNA-deficient human cells..” Rna 20, no. 6 (June 2014): 923–37. https://doi.org/10.1261/rna.044545.114.

PMID
24757167
Full Text

Whisnant, Adam W., Timo Kehl, Qiuying Bao, Magdalena Materniak, Jacek Kuzmak, Martin Löchelt, and Bryan R. Cullen. “Identification of novel, highly expressed retroviral microRNAs in cells infected by bovine foamy virus..” J Virol 88, no. 9 (May 2014): 4679–86. https://doi.org/10.1128/JVI.03587-13.

PMID
24522910
Full Text

Pan, Dongli, Omar Flores, Jennifer L. Umbach, Jean M. Pesola, Peris Bentley, Pamela C. Rosato, David A. Leib, Bryan R. Cullen, and Donald M. Coen. “A neuron-specific host microRNA targets herpes simplex virus-1 ICP0 expression and promotes latency..” Cell Host Microbe 15, no. 4 (April 9, 2014): 446–56. https://doi.org/10.1016/j.chom.2014.03.004.

PMID
24721573
Full Text

Flores, Omar, Edward M. Kennedy, Rebecca L. Skalsky, and Bryan R. Cullen. “Differential RISC association of endogenous human microRNAs predicts their inhibitory potential..” Nucleic Acids Res 42, no. 7 (April 2014): 4629–39. https://doi.org/10.1093/nar/gkt1393.

PMID
24464996
Full Text

Furuse, Yuki, Akbar Dastjerdi, Katharina Seilern-Moy, Falko Steinbach, and Bryan R. Cullen. “Analysis of viral microRNA expression by elephant endotheliotropic herpesvirus 1..” Virology 454–455 (April 2014): 102–8. https://doi.org/10.1016/j.virol.2014.02.009.

PMID
24725936
Full Text

Skalsky, Rebecca L., Dong Kang, Sarah D. Linnstaedt, and Bryan R. Cullen. “Evolutionary conservation of primate lymphocryptovirus microRNA targets..” J Virol 88, no. 3 (February 2014): 1617–35. https://doi.org/10.1128/JVI.02071-13.

PMID
24257599
Full Text

Parnas, Oren, David L. Corcoran, and Bryan R. Cullen. “Analysis of the mRNA targetome of microRNAs expressed by Marek's disease virus..” Mbio 5, no. 1 (January 21, 2014): e01060–e01013. https://doi.org/10.1128/mBio.01060-13.

PMID
24449754
Full Text

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