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

Martinez Campos, Cecilia, Kevin Tsai, David G. Courtney, Hal P. Bogerd, Christopher L. Holley, and Bryan R. Cullen. “Mapping of pseudouridine residues on cellular and viral transcripts using a novel antibody-based technique.” Rna 27, no. 11 (November 2021): 1400–1411. https://doi.org/10.1261/rna.078940.121.

PMID
34376564
Full Text

Tsai, Kevin, Hal P. Bogerd, Edward M. Kennedy, Ann Emery, Ronald Swanstrom, and Bryan R. Cullen. “Epitranscriptomic addition of m6A regulates HIV-1 RNA stability and alternative splicing.” Genes Dev 35, no. 13–14 (July 1, 2021): 992–1004. https://doi.org/10.1101/gad.348508.121.

PMID
34140354
Full Text

Irwan, Ishak D., and Bryan R. Cullen. “Tax Induces the Recruitment of NF-κB to Unintegrated HIV-1 DNA To Rescue Viral Gene Expression and Replication.” J Virol 95, no. 13 (June 10, 2021): e0028521. https://doi.org/10.1128/JVI.00285-21.

PMID
33883218
Full Text

Kelly, Megan L., Chia-Chieh Chu, Honglue Shi, Laura R. Ganser, Hal P. Bogerd, Kelly Huynh, Yuze Hou, Bryan R. Cullen, and Hashim M. Al-Hashimi. “Understanding the characteristics of nonspecific binding of drug-like compounds to canonical stem-loop RNAs and their implications for functional cellular assays.” Rna 27, no. 1 (January 2021): 12–26. https://doi.org/10.1261/rna.076257.120.

PMID
33028652
Full Text

Tsai, Kevin, Ananda Ayyappan Jaguva Vasudevan, Cecilia Martinez Campos, Ann Emery, Ronald Swanstrom, and Bryan R. Cullen. “Acetylation of Cytidine Residues Boosts HIV-1 Gene Expression by Increasing Viral RNA Stability.” Cell Host Microbe 28, no. 2 (August 12, 2020): 306-312.e6. https://doi.org/10.1016/j.chom.2020.05.011.

PMID
32533923
Full Text

Irwan, Ishak D., Heather L. Karnowski, Hal P. Bogerd, Kevin Tsai, and Bryan R. Cullen. “Reversal of Epigenetic Silencing Allows Robust HIV-1 Replication in the Absence of Integrase Function.” Mbio 11, no. 3 (June 2, 2020). https://doi.org/10.1128/mBio.01038-20.

PMID
32487757
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 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

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