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

Poling, BC, Tsai, K, Kang, D, Ren, L, Kennedy, EM, and Cullen, BR. "A lentiviral vector bearing a reverse intron demonstrates superior expression of both proteins and microRNAs." RNA biology 14, no. 11 (November 2017): 1570-1579.

PMID
28594311
Full Text

Courtney, DG, Kennedy, EM, Dumm, RE, Bogerd, HP, Tsai, K, Heaton, NS, and Cullen, BR. "Epitranscriptomic Enhancement of Influenza A Virus Gene Expression and Replication." Cell host & microbe 22, no. 3 (September 2017): 377-386.e5.

PMID
28910636
Full Text

Cullen, BR. "RNA Interference in Mammals: The Virus Strikes Back." Immunity 46, no. 6 (June 2017): 970-972.

PMID
28636964
Full Text

Kennedy, EM, Courtney, DG, Tsai, K, and Cullen, BR. "Viral Epitranscriptomics." Journal of virology 91, no. 9 (May 2017). (Review)

PMID
28250115
Full Text

Kennedy, EM, Kornepati, AVR, Bogerd, HP, and Cullen, BR. "Partial reconstitution of the RNAi response in human cells using Drosophila gene products." RNA (New York, N.Y.) 23, no. 2 (February 2017): 153-160.

PMID
27837013
Full Text

Bogerd, HP, Kennedy, EM, Whisnant, AW, and Cullen, BR. "Induced Packaging of Cellular MicroRNAs into HIV-1 Virions Can Inhibit Infectivity." mBio 8, no. 1 (January 17, 2017).

PMID
28096489
Full Text

Kennedy, EM, and Cullen, BR. "Gene Editing: A New Tool for Viral Disease." Annual review of medicine 68 (January 2017): 401-411.

PMID
27576009
Full Text

"Correction for Kennedy et al., Production of functional small interfering RNAs by an amino-terminal deletion mutant of human Dicer." Proceedings of the National Academy of Sciences 113, no. 42 (October 18, 2016): E6547-E6547.

Full Text

Kennedy, EM, Bogerd, HP, Kornepati, AVR, Kang, D, Ghoshal, D, Marshall, JB, Poling, BC, Tsai, K, Gokhale, NS, Horner, SM, and Cullen, BR. "Posttranscriptional m(6)A Editing of HIV-1 mRNAs Enhances Viral Gene Expression." Cell host & microbe 19, no. 5 (May 2016): 675-685.

PMID
27117054
Full Text

Aghajan, H, Augusto, JC, Prati, A, and Gomez, C. Preface. April 27, 2016.

Full Text

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