Bryan Cullen, PhD
Principal Investigator
James B. Duke Distinguished Professor of Molecular Genetics and Microbiology
Director, Center for Virology
Professor of Molecular Genetics and Microbiology
Professor in Medicine
Member of the Duke Cancer Institute
Contact Information

Box 3025 DUMC
Durham, N.C. 27710
Phone: (919) 684-3369
Fax: (919) 681-8979
Email: bryan.cullen@duke.edu

Location
424 CARL Building

Research

While my laboratory has for several years been a leader in research directed at identifying viral microRNAs and discovering their contributions to viral replication and pathogenicity, this work has now largely ended as departing postdocs have taken their viral microRNA projects with them to their own laboratories. Instead, our work is now broadly focused on two fairly new areas. Firstly, we have been working on optimizing CRISPR/Cas-based gene editing strategies as a way to treat diseases caused by several pathogenic human viruses, including HIV-1, human papillomavirus (HPV), hepatitis B virus (HBV) and herpes simplex virus. This work has led to a number of publications and also to a patent application. Secondly, my laboratory has recently become very interested in epitranscriptomic regulation of viral gene expression, that is how covalent modifications that are added co-transcriptionally to mRNAs at the single nucleotide level, including particularly addition of a methyl group at the N6 position of adenosine (m6A), affect viral replication and pathogenesis. The level of m6A found on viral mRNAs is substantially higher than seen on cellular mRNAs, suggesting that viruses have evolved to efficiently recruit the cellular methyltransferases that generate m6A. In fact, we have recently reported in three high profile manuscripts that m6A addition not only facilitates viral gene expression and replication but also increases viral pathogenicity in vivo. Going forward, we anticipate that investigation of m6A function in a viral context, as well as research into other RNA modifications, such as m5C and 2’OMe, that are found at high levels on viral RNAs, will form a major part of our research efforts.

Biography

Bryan R. Cullen obtained a B.Sc. in Biochemistry from Warwick University in the UK and a M.Sc. in Virology from the University of Birmingham before moving to the USA, where he obtained a Ph.D. in Microbiology from Rutgers University. In 1987, he was recruited to Duke University Medical Center as a Howard Hughes Medical Institute Investigator. He currently holds a James B. Duke Professorship in the Department of Molecular Genetics and Microbiology at Duke. Dr. Cullen’s research interests have historically revolved around the use of viruses as genetic tools to understand aspects of the biology of the eukaryotic cell, focusing particularly on RNA-sequence mediated gene regulation. Currently, his laboratory is studying the regulation of viral mRNA expression by epitranscriptomic modifications and the use of CRISPR/Cas as a potential approach to the treatment of chronic diseases caused by DNA viruses. Dr. Cullen has published over 315 research papers, is on the editorial board of 11 prominent journals and has been recognized as one of the most highly cited scientists in the field of microbiology.

Honors & Awards

•Recipient of the 1989 Eli Lilly Molecular Biology Contact Award

•Recipient of a 1993 Alexander von Humboldt Foundation Research Award

•Listed as one of the 10 most cited AIDS researchers by Science (Heavy Hitters in AIDS, Vol. 260, p. 1262, 1993)

•Recipient of the University of Medicine and Dentistry of New Jersey Distinguished Alumni Award (2000)

•Awarded the distinguished professorship James B. Duke Professor of Genetics (2000)
Listed as one of the world’s most “Highly Cited Researchers” by the Institute for Scientific Information (2001) [http://isihighlycited.com]

•Appointed to the honorary position of “Visiting Professor,” by the Imperial College of Science, Technology and Medicine, London, UK (2002)

•Awarded a Distinguished Fellowship at the Institute of Advanced Studies (IAS) at Durham University, U.K. (2007)

•Elected to Fellowship in the American Academy of Microbiology (2009)

•Bernard Fields Memorial Lectureship, 2011 Conference on Retroviruses and Opportunisitic Infections

•Elected to the rank of Fellow of the American Association for the Advancement of Science (AAAS) (2011)

•Awarded a Visiting Professorship by the Institute of Advanced Studies (IAS) at the University of Warwick, UK (2012)

•Recipient of the 2013 Research Mentoring Award for Basic Science Research, Duke University Medical Center (2013)

•Listed asbeing in top 1% of the world’s most “Highly Cited Researchers” by Thomson Reuters and Clarivate Analytics at Web of Science (2001-present) [http://highlycited.com].

•Raymond Schinazi Distinguished Lectureship, Emory University School of Medicine, Atlanta, Georgia (2014)

PLoS Pathogens selected two manuscripts from the Cullen laboratory (#220 and #269) as among the most important published in the first ten years of the journal’s existence (42 total and 11 virology manuscripts were chosen)

•Honorary doctorate of science (D.Sc.) awarded by Warwick University, UK (2016).

Lab Members

Research Scientist
Postdoctoral Fellow

Publications

Google Scholar Profile

Representative Publications: 

Zeng, Y., Wagner, E.J., and Cullen, B.R. (2002). Both natural and designed micro RNAs can inhibit the expression of cognate mRNAs when expressed in human cells. Mol Cell, 9:1327-1333.

Bogerd, H.P., Doehle, B.P., Wiegand, H.L., and Cullen, B.R. (2004). A single amino acid difference in the host APOBEC3G protein controls the primate species specificity of HIV type 1 virion infectivity factor. Proc Natl Acad Sci. USA, 101:3770-3774.

Cai, X., Hagedorn, C.H., and Cullen, B.R. (2004).   Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA, 10:1957-1966.

Zeng, Y., Yi, R., and Cullen, B.R. (2005). Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme drosha. EMBO J, 24:138-148.

Cai, X., Lu, S., Zhihong, Z., Gonzalez, C.M., Damania, B., and Cullen, B.R. (2005). Kaposi’s sarcoma-associated herpesvirus expresses an array of novel viral microRNAs in latently infected cells. Proc Natl Acad Sci. USA, 102:5570-5575.

Cai, X., Schäfer, A., Lu, S., Bilello, J.P., Desrosiers, R.C., Edwards, R., Raab-Traub, N., and Cullen, B.R. (2006). Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed. PLoS Pathogens, 2:e23.

Bogerd, H.P., Wiegand, H.L., Hulme, A.E., Garcia-Perez, J.L., O’Shea, K.S., Moran, J.V., and Cullen, B.R. (2006). Cellular inhibitors of long interspersed element 1 and Alu retrotransposition. Proc Natl Acad Sci. USA, 103:8780-8785.

Lin, J. and Cullen, B.R. (2007). Analysis of the interaction of primate retroviruses with the human RNA interference machinery. Journal of Virology, 81:12218-12226.

Gottwein, E., Mukherjee, N., Sachse, C., Frenzel, C., Majoros, W.H., Chi, J.-T.A., Braich, R., Manoharan, M., Soutschek, J., Ohler, U., and Cullen, B.R. (2007). A viral microRNA functions as an ortholog of cellular miR-155. Nature, 450:1096-1099.

Umbach, J.L., Kramer, M.F., Jurak, I., Karnowski, H.W., Coen, D.m., and Cullen, B.R. (2008). MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs. Nature, 454:780-783.

Gottwein, E. and Cullen, B.R. (2008). Viral and cellular microRNAs as determinants of viral pathogenesis and immunity. Cell Host Microbe, 3:375-387.

Cullen, B.R. (2009). Viral and cellular messenger RNA targets of viral microRNAs. Nature, 457:421-425.

Cullen, B.R. (2009). Viral RNAs: Lessons from the enemy. Cell, 136:592-597.

Umbach, J.L. and Cullen, B.R. (2009). The role of RNAi and microRNAs in animal virus replication and antiviral immunity. Genes Dev, 23:1151-1164.

Gottwein, E. and Cullen, B.R. (2010). A human herpesvirus microRNA inhibits p21 expression and attentuates p21-mediated cell cycle arrest. J Virol, 84:5229-5237.

Bogerd, H.P., Karnowski, H.W., Cai, X., Shin, J., Pholers, M., and Cullen, B.R. (2010). A mammalian herpesvirus uses noncanonical expression and processing mechanisms to generate viral MicroRNAs. Mol Cell, 37:135-142.

Bogerd, H.P., Karnowski, H.W., Cai, X., Shin, J., Pholers, M., and Cullen, B.R. (2010). A mammalian herpesvirus uses noncanonical expression and processing mechanisms to generate viral MicroRNAs. Mol Cell, 37:135-142.

Cullen, B.R. (2011). Viruses and microRNAs: RISCy interactions with serious consequences. Genes Dev; 25:1881-1894. PMCID: 3185961.

Gottwein, E., Corcoran, D.L., Mukherjee, N., Skalsky, R.L., Hafner, M., Nusbaum, J.D., Shamulailatpam, P., Love, C.L., Dave, S.S., Tuschl, T., Ohler, U. and Cullen, B.R. (2011). Viral microRNA targetome of KSHV-infected primary effusion lymphoma cell lines. Cell Host Microbe; 10:515-526. PMCID: 3222872.

Skalsky, R.L., Corcoran, D.L., Gottwein, E., Frank, C.L., Kang, D., Hafner, M., Nusbaum, J.D., Feederle, R., Delecluse, H.J., Luftig, M.A., Tuschl, T., Ohler, U. and Cullen, B.R. (2012). The viral and cellular microRNA targetome in lymphoblastoid cell lines. PLoS Pathog; 8:e1002484. PMCID: 3266933.

Feederle, R., Linnstaedt, S.D., Bannert, H., Lips, H., Bencun, M., Cullen, B.R. and Delecluse, H.J. (2011). A viral microRNA cluster strongly potentiates the transforming properties of a human herpesvirus. PLoS Pathog; 7:e1001294. PMCID: 3040666.

Kennedy, Edward M., Bogerd, Hal P., Kornepati, Anand V.R., Kang, Dong, Ghoshal, Delta, Marshall, Joy B., Poling, Brigid C., Tsai, Kevin, Gokhale, Nandan S., Horner, Stacy M. and Cullen, Bryan R. (2016). Posttranscriptional m6A Editing of HIV-1 mRNAs Enhances Viral Gene Expression. Cell Host and Microbe, 19: 675-685

Kennedy, Edward M. and Cullen, Bryan R. (2017) Gene Editing: A New Tool for Viral Disease. Annual Review of Medicine, 68: 401-411.

Kennedy, Edward M., Kornepati, Anand V., Bogerd, Hal P. and Cullen, Bryan R. (2017) Partial reconstitution of the RNAi response in human cells using Drosophila gene products. RNA, 23: 153-160.

Bogerd, Hal P., Kennedy, Edward M., Whisnant, Adam W. and Cullen, Bryan R. (2017) Induced packaging of cellular microRNAs into HIV-1 virions can inhibit infectivity. mBio, 8: e02125-16.

Kennedy, Edward M., Courtney, David G., Tsai, Kevin and Cullen, Bryan R. (2017) Viral epitranscriptomics. Journal of Virology, 91: e02263-16.

Poling, Brigid C., Tsai, Kevin, Kang, Dong, Ren, Linda, Kennedy, Edward M. and Cullen, Bryan R. (2017) A lentiviral vector bearing a reverse intron demonstrates superior expression of both proteins and microRNAs. RNA Biology. 1-10. doi:10.1080/15476286.2017.1334755.

Courtney, David G., Kennedy, Edward M., Dumm, Rebekah E., Bogerd, Hal P., Tsai, Kevin, Heaton, Nicholas S. and Cullen, Bryan R. (2017) Epitranscriptomic enhancement of influenza A virus gene expression and replication. Cell Host & Microbe, 22: 377-386.e5.

Cullen, Bryan R. (2017) RNA interference in mammals: The virus strikes back. Immunity, 46: 970-972.

Poling, Brigid C., Price, Alexander M., Luftig, Micah A. and Cullen, Bryan R. (2017). The Epstein-Barr virus miR-BHRF1 microRNAs regulate viral gene expression in cis. Virology, 512: 113-123.

Heaton, Nicholas S. and Cullen, Bryan R. (2017) Viruses hijack a long non-coding RNA. Nature, 552: 184-185.

Tsai, Kevin, Courtney, David G. and Cullen, Bryan R. (2018) Addition of m6A to SV40 late mRNAs enhances viral structural gene expression and replication. PLoS Pathogens 14: e1006919.