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

Kennedy, E. M., A. W. Whisnant, A. V. R. Kornepati, J. B. Marshall, H. P. Bogerd, and B. R. Cullen. “Erratum: Production of functional small interfering RNAs by an amino-terminal deletion mutant of human Dicer (Proceedings of the National Academy of Sciences of the United States of America (2015) 112: 50 (E6945-E6954) DOI: 10.1073/pnas.1513421112).” Proceedings of the National Academy of Sciences of the United States of America 113, no. 42 (October 18, 2016). https://doi.org/10.1073/pnas.1615446113.

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Kennedy, Edward M., Hal P. Bogerd, Anand V. R. Kornepati, Dong Kang, Delta Ghoshal, Joy B. Marshall, Brigid C. Poling, et al. “Posttranscriptional m(6)A Editing of HIV-1 mRNAs Enhances Viral Gene Expression..” Cell Host Microbe 19, no. 5 (May 11, 2016): 675–85. https://doi.org/10.1016/j.chom.2016.04.002.

PMID
27117054
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Bogerd, Hal P., Anand V. R. Kornepati, Joy B. Marshall, Edward M. Kennedy, and Bryan R. Cullen. “Specific induction of endogenous viral restriction factors using CRISPR/Cas-derived transcriptional activators..” Proc Natl Acad Sci U S A 112, no. 52 (December 29, 2015): E7249–56. https://doi.org/10.1073/pnas.1516305112.

PMID
26668372
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Kennedy, Edward M., Adam W. Whisnant, Anand V. R. Kornepati, Joy B. Marshall, Hal P. Bogerd, and Bryan R. Cullen. “Production of functional small interfering RNAs by an amino-terminal deletion mutant of human Dicer..” Proc Natl Acad Sci U S A 112, no. 50 (December 15, 2015): E6945–54. https://doi.org/10.1073/pnas.1513421112.

PMID
26621737
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Kennedy, Edward M., Anand V. R. Kornepati, Adam L. Mefferd, Joy B. Marshall, Kevin Tsai, Hal P. Bogerd, and Bryan R. Cullen. “Optimization of a multiplex CRISPR/Cas system for use as an antiviral therapeutic..” Methods 91 (December 2015): 82–86. https://doi.org/10.1016/j.ymeth.2015.08.012.

PMID
26291065
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Friedland, Ari E., Reshica Baral, Pankhuri Singhal, Katherine Loveluck, Shen Shen, Minerva Sanchez, Eugenio Marco, et al. “Characterization of Staphylococcus aureus Cas9: a smaller Cas9 for all-in-one adeno-associated virus delivery and paired nickase applications..” Genome Biol 16 (November 24, 2015). https://doi.org/10.1186/s13059-015-0817-8.

PMID
26596280
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Gregorovic, Goran, Elizabeth A. Boulden, Rachel Bosshard, Claudio Elgueta Karstegl, Rebecca Skalsky, Bryan R. Cullen, Cornelia Gujer, Patrick Rämer, Christian Münz, and Paul J. Farrell. “Epstein-Barr Viruses (EBVs) Deficient in EBV-Encoded RNAs Have Higher Levels of Latent Membrane Protein 2 RNA Expression in Lymphoblastoid Cell Lines and Efficiently Establish Persistent Infections in Humanized Mice..” J Virol 89, no. 22 (November 2015): 11711–14. https://doi.org/10.1128/JVI.01873-15.

PMID
26339045
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Mefferd, Adam L., Anand V. R. Kornepati, Hal P. Bogerd, Edward M. Kennedy, and Bryan R. Cullen. “Expression of CRISPR/Cas single guide RNAs using small tRNA promoters..” Rna 21, no. 9 (September 2015): 1683–89. https://doi.org/10.1261/rna.051631.115.

PMID
26187160
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