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

Courtney, David G., Kevin Tsai, Hal P. Bogerd, Edward M. Kennedy, Brittany A. Law, Ann Emery, Ronald Swanstrom, Christopher L. Holley, and Bryan R. Cullen. “Epitranscriptomic Addition of m5C to HIV-1 Transcripts Regulates Viral Gene Expression..” Cell Host Microbe 26, no. 2 (August 14, 2019): 217-227.e6. https://doi.org/10.1016/j.chom.2019.07.005.

PMID
31415754
Full Text

Courtney, David G., Andrea Chalem, Hal P. Bogerd, Brittany A. Law, Edward M. Kennedy, Christopher L. Holley, and Bryan R. Cullen. “Extensive Epitranscriptomic Methylation of A and C Residues on Murine Leukemia Virus Transcripts Enhances Viral Gene Expression..” Mbio 10, no. 3 (June 11, 2019). https://doi.org/10.1128/mBio.01209-19.

PMID
31186331
Full Text

Courtney, David G., Kevin Tsai, Hal P. Bogerd, Edward M. Kennedy, Brittany A. Law, Ann Emery, Ronald Swanstrom, Christopher L. Holley, and Bryan R. Cullen. “Epitranscriptomic Regulation of HIV-1 Gene Expression by m 5C and the Novel m 5C Reader MBD2,” February 15, 2019.

Scholars@Duke

Tsai, Kevin, David G. Courtney, Edward M. Kennedy, and Bryan R. Cullen. “Influenza A virus-derived siRNAs increase in the absence of NS1 yet fail to inhibit virus replication..” Rna 24, no. 9 (September 2018): 1172–82. https://doi.org/10.1261/rna.066332.118.

PMID
29903832
Full Text

Mefferd, Adam L., Hal P. Bogerd, Ishak D. Irwan, and Bryan R. Cullen. “Insights into the mechanisms underlying the inactivation of HIV-1 proviruses by CRISPR/Cas..” Virology 520 (July 2018): 116–26. https://doi.org/10.1016/j.virol.2018.05.016.

PMID
29857168
Full Text

Hsu, David S., Anand Vr Kornepati, Wayne Glover, Edward M. Kennedy, and Bryan R. Cullen. “Targeting HPV16 DNA using CRISPR/Cas inhibits anal cancer growth in vivo..” Future Virol 13, no. 7 (July 2018): 475–82. https://doi.org/10.2217/fvl-2018-0010.

PMID
30245733
Full Text

Mefferd, Adam L., Anand V. R. Kornepati, Hal P. Bogerd, Edward M. Kennedy, and Bryan R. Cullen. “Expression of CRISPR-Cas9 Single Guide RNA's Using Small tRNA Promoters.” In Molecular Therapy, 26:229–229. CELL PRESS, 2018.

Scholars@Duke

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