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, EM, Bassit, LC, Mueller, H, Kornepati, AVR, Bogerd, HP, Nie, T, Chatterjee, P, Javanbakht, H, Schinazi, RF, and Cullen, BR. "Suppression of hepatitis B virus DNA accumulation in chronically infected cells using a bacterial CRISPR/Cas RNA-guided DNA endonuclease." Virology 476 (February 2015): 196-205.

PMID
25553515
Full Text

Skalsky, RL, and Cullen, BR. "EBV Noncoding RNAs." Current Topics in Microbiology and Immunology 391 (January 2015): 181-217. (Review)

PMID
26428375
Full Text

Friedland, AE, Baral, R, Singhal, P, Loveluck, K, Shen, S, Sanchez, M, Marco, E, Gotta, GM, Maeder, ML, Kennedy, EM, Kornepati, AVR, Sousa, A, Collins, MA, Jayaram, H, Cullen, BR, and Bumcrot, D. "Characterization of Staphylococcus aureus Cas9: a smaller Cas9 for all-in-one adeno-associated virus delivery and paired nickase applications." Genome Biology 16 (January 2015): 257-null.

PMID
26596280
Full Text

Renugopalakrishnan, V, Koester, SJ, McDevitt, MR, Ajayan, PM, Liepmann, D, Demirci, U, Paulmurugan, R, and Viswanathan, S. "Preface." Materials Research Society Symposium Proceedings 1725 (January 1, 2015).

Full Text

Cullen, BR. "Viruses and RNA interference: issues and controversies." Journal of Virology 88, no. 22 (November 2014): 12934-12936. (Review)

PMID
25210170
Full Text

Cullen, BR. "HIV-1 Packing to Leave." Cell 159, no. 5 (November 2014): 975-976.

PMID
25416937
Full Text

Kennedy, EM, Kornepati, AVR, Goldstein, M, Bogerd, HP, Poling, BC, Whisnant, AW, Kastan, MB, and Cullen, BR. "Inactivation of the human papillomavirus E6 or E7 gene in cervical carcinoma cells by using a bacterial CRISPR/Cas RNA-guided endonuclease." Journal of Virology 88, no. 20 (October 2014): 11965-11972.

PMID
25100830
Full Text

Bogerd, HP, Skalsky, RL, Kennedy, EM, Furuse, Y, Whisnant, AW, Flores, O, Schultz, KLW, Putnam, N, Barrows, NJ, Sherry, B, Scholle, F, Garcia-Blanco, MA, Griffin, DE, and Cullen, BR. "Replication of many human viruses is refractory to inhibition by endogenous cellular microRNAs." Journal of Virology 88, no. 14 (July 2014): 8065-8076.

PMID
24807715
Full Text

Bogerd, HP, Whisnant, AW, Kennedy, EM, Flores, O, and Cullen, BR. "Derivation and characterization of Dicer- and microRNA-deficient human cells." Rna (New York, N.Y.) 20, no. 6 (June 2014): 923-937.

PMID
24757167
Full Text

Skalsky, RL, Olson, KE, Blair, CD, Garcia-Blanco, MA, and Cullen, BR. "A "microRNA-like" small RNA expressed by Dengue virus?." Proceedings of the National Academy of Sciences of the United States of America 111, no. 23 (June 2014): E2359-. (Letter)

PMID
24853506
Full Text

Pages