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, and Bryan R. Cullen. “A human herpesvirus microRNA inhibits p21 expression and attenuates p21-mediated cell cycle arrest..” J Virol 84, no. 10 (May 2010): 5229–37. https://doi.org/10.1128/JVI.00202-10.

PMID
20219912
Full Text

Kelly, Elizabeth J., Elizabeth M. Hadac, Bryan R. Cullen, and Stephen J. Russell. “MicroRNA antagonism of the picornaviral life cycle: alternative mechanisms of interference..” Plos Pathog 6, no. 3 (March 19, 2010). https://doi.org/10.1371/journal.ppat.1000820.

PMID
20333250
Full Text

Skalsky, Rebecca L., Dana L. Vanlandingham, Frank Scholle, Stephen Higgs, and Bryan R. Cullen. “Identification of microRNAs expressed in two mosquito vectors, Aedes albopictus and Culex quinquefasciatus..” Bmc Genomics 11 (February 18, 2010). https://doi.org/10.1186/1471-2164-11-119.

PMID
20167119
Full Text

Bogerd, Hal P., Heather W. Karnowski, Xuezhong Cai, Jinwook Shin, Michael Pohlers, and Bryan R. Cullen. “A mammalian herpesvirus uses noncanonical expression and processing mechanisms to generate viral MicroRNAs..” Mol Cell 37, no. 1 (January 15, 2010): 135–42. https://doi.org/10.1016/j.molcel.2009.12.016.

PMID
20129062
Full Text

Umbach, Jennifer L., and Bryan R. Cullen. “In-depth analysis of Kaposi's sarcoma-associated herpesvirus microRNA expression provides insights into the mammalian microRNA-processing machinery..” J Virol 84, no. 2 (January 2010): 695–703. https://doi.org/10.1128/JVI.02013-09.

PMID
19889781
Full Text

Umbach, Jennifer L., Kening Wang, Shuang Tang, Philip R. Krause, Erik K. Mont, Jeffrey I. Cohen, and Bryan R. Cullen. “Identification of viral microRNAs expressed in human sacral ganglia latently infected with herpes simplex virus 2..” J Virol 84, no. 2 (January 2010): 1189–92. https://doi.org/10.1128/JVI.01712-09.

PMID
19889786
Full Text

Umbach, Jennifer L., Maria A. Nagel, Randall J. Cohrs, Donald H. Gilden, and Bryan R. Cullen. “Analysis of human alphaherpesvirus microRNA expression in latently infected human trigeminal ganglia..” J Virol 83, no. 20 (October 2009): 10677–83. https://doi.org/10.1128/JVI.01185-09.

PMID
19656888
Full Text

Umbach, Jennifer L., and Bryan R. Cullen. “The role of RNAi and microRNAs in animal virus replication and antiviral immunity..” Genes Dev 23, no. 10 (May 15, 2009): 1151–64. https://doi.org/10.1101/gad.1793309.

PMID
19451215
Full Text

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