Bryan R. Cullen

Last updated
Bryan R. Cullen
Born
Bryan Richard Cullen

December 1951 (age 70–71)
Bradford, England
NationalityBritish
Alma mater Rutgers University
Scientific career
Fields Molecular Genetics
Microbiology
Institutions Duke University

Bryan Richard Cullen is a James B. Duke Professor of Molecular Genetics and Microbiology at Duke University Medical Center in Durham, North Carolina. Cullen was the Founding Director of the Duke University Center for Virology. [1]

Contents

Early life and education

Cullen was born in December 1951 in Bradford, England, where he graduated head of his class from Thornton Grammar School in 1970. In 1973, he received a B.Sc. in biochemistry from Warwick University, England and in 1974, he received an M.Sc. in virology from Birmingham University, England. Dr. Cullen emigrated to the US in 1974, where he received a Ph.D. in microbiology from Rutgers University, New Jersey, in 1984. He became a US citizen in 1992. [2]

Research

Cullen and his laboratory are currently 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. [3] [4]

Cullen discovered the phenomenon of “transcriptional interference” in retroviruses and showed that this explained why proviral 5’LTRs are active while 3’ LTRs are silenced. [5] After starting his own research group in 1984, he demonstrated that the HIV-1 Tat protein activates viral transcription and that the HIV-1 Rev protein induces viral RNA nuclear export. [6] [7] [8] [9] He demonstrated that HIV-1 readily infects non-dividing cells, [10] an unexpected result that overturned then prevalent dogma, and showed that a single variable loop in the Envelope protein, the V3 loop, controls HIV-1 tissue tropism. [11]

His laboratory was the first to express and functionally characterize microRNAs in mammalian cells and the first to identify and functionally characterize the microRNAs encoded by the herpesviruses KHSV, EBV and HSV-1. [12] [13] [14] [15]

Recently, his laboratory was the first to report that several distinct epitranscriptomic modifications added to viral mRNAs promote viral gene expression and replication. [3] [16]

Controversy

On May 24, 2022, Cullen replied-all to a department-wide email about an inclusivity module by claiming that it is a "left-wing Maoist political propaganda workshop" and that he will refuse to engage in it "as a tenured faculty". He was widely criticized in the same email chain, where he was also perceived to be transphobic. [17]

Awards and honors

Cullen was the recipient of the 1989 Ely Lilly Molecular Biology Award. [18] [19] He was awarded a distinguished fellowship by Durham University, UK in 2007. [20] He is a Fellow of the American Academy of Microbiology since 2009 and of the American Association for the Advancement of Science since 2011. [21] [22] He was named one of the top peer reviewers by the Journal of Virology in 2009 and 2011 and has been identified as a highly cited scientist by both Clarivate Analytics at Web of Science and by Thomson Reuters annually since 2001. [23] He was awarded an honorary doctorate of science (D.Sc.) degree by Warwick University in 2016.

Key publications

Editorship

Dr. Cullen has served as an Associate Editor for Cell, and PLoS Pathogens. [26] He has also served as an editorial board member for several major journals.

Related Research Articles

<span class="mw-page-title-main">HIV</span> Human retrovirus, cause of AIDS

The human immunodeficiency viruses (HIV) are two species of Lentivirus that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment, average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype.

The genome and proteins of HIV have been the subject of extensive research since the discovery of the virus in 1983. "In the search for the causative agent, it was initially believed that the virus was a form of the Human T-cell leukemia virus (HTLV), which was known at the time to affect the human immune system and cause certain leukemias. However, researchers at the Pasteur Institute in Paris isolated a previously unknown and genetically distinct retrovirus in patients with AIDS which was later named HIV." Each virion comprises a viral envelope and associated matrix enclosing a capsid, which itself encloses two copies of the single-stranded RNA genome and several enzymes. The discovery of the virus itself occurred two years following the report of the first major cases of AIDS-associated illnesses.

<span class="mw-page-title-main">Virus latency</span> Ability of some viruses to lie dormant within a cell

Virus latency is the ability of a pathogenic virus to lie dormant within a cell, denoted as the lysogenic part of the viral life cycle. A latent viral infection is a type of persistent viral infection which is distinguished from a chronic viral infection. Latency is the phase in certain viruses' life cycles in which, after initial infection, proliferation of virus particles ceases. However, the viral genome is not eradicated. The virus can reactivate and begin producing large amounts of viral progeny without the host becoming reinfected by new outside virus, and stays within the host indefinitely.

<span class="mw-page-title-main">Sp1 transcription factor</span> Protein-coding gene in the species Homo sapiens

Transcription factor Sp1, also known as specificity protein 1* is a protein that in humans is encoded by the SP1 gene.

Antigenic variation or antigenic alteration refers to the mechanism by which an infectious agent such as a protozoan, bacterium or virus alters the proteins or carbohydrates on its surface and thus avoids a host immune response, making it one of the mechanisms of antigenic escape. It is related to phase variation. Antigenic variation not only enables the pathogen to avoid the immune response in its current host, but also allows re-infection of previously infected hosts. Immunity to re-infection is based on recognition of the antigens carried by the pathogen, which are "remembered" by the acquired immune response. If the pathogen's dominant antigen can be altered, the pathogen can then evade the host's acquired immune system. Antigenic variation can occur by altering a variety of surface molecules including proteins and carbohydrates. Antigenic variation can result from gene conversion, site-specific DNA inversions, hypermutation, or recombination of sequence cassettes. The result is that even a clonal population of pathogens expresses a heterogeneous phenotype. Many of the proteins known to show antigenic or phase variation are related to virulence.

Env is a viral gene that encodes the protein forming the viral envelope. The expression of the env gene enables retroviruses to target and attach to specific cell types, and to infiltrate the target cell membrane.

Visna-maedi virus from the genus Lentivirus and subfamily Orthoretrovirinae, is a retrovirus that causes encephalitis and chronic pneumonitis in sheep. It is known as visna when found in the brain, and maedi when infecting the lungs. Lifelong, persistent infections in sheep occur in the lungs, lymph nodes, spleen, joints, central nervous system, and mammary glands; The condition is sometimes known as ovine progressive pneumonia (OPP), particularly in the United States, or Montana sheep disease. White blood cells of the monocyte/macrophage lineage are the main target of the virus.

The HIV-1 Rev response element (RRE) is a highly structured, ~350 nucleotide RNA segment present in the Env coding region of unspliced and partially spliced viral mRNAs. In the presence of the HIV-1 accessory protein Rev, HIV-1 mRNAs that contain the RRE can be exported from the nucleus to the cytoplasm for downstream events such as translation and virion packaging.

<span class="mw-page-title-main">Trans-activation response element (TAR)</span>

The HIV trans-activation response (TAR) element is an RNA element which is known to be required for the trans-activation of the viral promoter and for virus replication. The TAR hairpin is a dynamic structure that acts as a binding site for the Tat protein, and this interaction stimulates the activity of the long terminal repeat promoter.

<span class="mw-page-title-main">EIF5A</span> Protein-coding gene in humans

Eukaryotic translation initiation factor 5A-1 is a protein that in humans is encoded by the EIF5A gene.

<span class="mw-page-title-main">PSMF1</span> Protein found in humans

Proteasome inhibitor PI31 subunit is a protein that in humans is encoded by the PSMF1 gene.

<span class="mw-page-title-main">PSME4</span> Protein found in humans

Proteasome activator complex subunit 4 is a protein that in humans is encoded by the PSME4 gene.

<span class="mw-page-title-main">PRKACB</span> Protein-coding gene in the species Homo sapiens

cAMP-dependent protein kinase catalytic subunit beta is an enzyme that in humans is encoded by the PRKACB gene.

<span class="mw-page-title-main">AGFG1</span>

Arf-GAP domain and FG repeat-containing protein 1 is a protein that in humans is encoded by the AGFG1 gene.

<span class="mw-page-title-main">PRKACG</span> Protein-coding gene in the species Homo sapiens

cAMP-dependent protein kinase catalytic subunit gamma is an enzyme that in humans is encoded by the PRKACG gene.

Tat (HIV)

In molecular biology, Tat is a protein that is encoded for by the tat gene in HIV-1. Tat is a regulatory protein that drastically enhances the efficiency of viral transcription. Tat stands for "Trans-Activator of Transcription". The protein consists of between 86 and 101 amino acids depending on the subtype. Tat vastly increases the level of transcription of the HIV dsDNA. Before Tat is present, a small number of RNA transcripts will be made, which allow the Tat protein to be produced. Tat then binds to cellular factors and mediates their phosphorylation, resulting in increased transcription of all HIV genes, providing a positive feedback cycle. This in turn allows HIV to have an explosive response once a threshold amount of Tat is produced, a useful tool for defeating the body's response.

<span class="mw-page-title-main">Rev (HIV)</span> HIV-1 regulating protein

Rev is a transactivating protein that is essential to the regulation of HIV-1 protein expression. A nuclear localization signal is encoded in the rev gene, which allows the Rev protein to be localized to the nucleus, where it is involved in the export of unspliced and incompletely spliced mRNAs. In the absence of Rev, mRNAs of the HIV-1 late (structural) genes are retained in the nucleus, preventing their translation.

Within the field of molecular biology, the epitranscriptome includes all the biochemical modifications of the RNA within a cell. In analogy to epigenetics that describes "functionally relevant changes to the genome that do not involve a change in the nucleotide sequence", epitranscriptomics involves all functionally relevant changes to the transcriptome that do not involve a change in the ribonucleotide sequence. Thus, the epitranscriptome can be defined as the ensemble of such functionally relevant changes.

Paul Darren Bieniasz is a British-American virologist whose main area of research is HIV/AIDS. He is currently a professor of retrovirology at the Rockefeller University. He received the 2015 KT Jeang Retrovirology Prize and the 2010 Eli Lilly and Company Research Award. Bieniasz has been a Howard Hughes Medical Institute investigator since 2008.

<span class="mw-page-title-main">Alex K. Shalek</span> Biomedical engineer

Alex K. Shalek is a biomedical engineer, and a core faculty member of the Institute for Medical Engineering and Science (IMES), an Associate Professor of Chemistry, and an Extramural Member of the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology. Additionally, he is a Member of the Ragon Institute and an Institute Member of the Broad Institute, an Assistant in Immunology at Massachusetts General Hospital, and an Instructor in Health Sciences and Technology at Harvard Medical School. The multi-disciplinary research of the Shalek Lab aims to create and implement broadly-applicable methods to study and engineer cellular responses in tissues, to drive biological discovery and improve prognostics, diagnostics, and therapeutics for autoimmune, infectious, and cancerous diseases. Shalek and his lab are best known for their work in single-cell genomics and for studying a number of devastating, but difficult to study, human diseases with partners around the world.

References

  1. ↑ "MGM Bryan Cullen, PhD". mgm.duke.edu. Retrieved 2019-09-14.
  2. ↑ Cullen, Bryan R (2014-04-01). "Interview with Bryan R Cullen". Future Virology. 9 (4): 345–350. doi:10.2217/fvl.14.17. ISSN   1746-0794.
  3. 1 2 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.; Cullen, Bryan R. (2017-12-13). "Posttranscriptional m6A Editing of HIV-1 mRNAs Enhances Viral Gene Expression". Cell Host & Microbe. 22 (6): 830. doi:10.1016/j.chom.2017.11.010. ISSN   1931-3128. PMC   5746179 . PMID   29241043.
  4. ↑ Courtney, David G.; Kennedy, Edward M.; Dumm, Rebekah E.; Bogerd, Hal P.; Tsai, Kevin; Heaton, Nicholas S.; Cullen, Bryan R. (2017-09-13). "Epitranscriptomic Enhancement of Influenza A Virus Gene Expression and Replication". Cell Host & Microbe. 22 (3): 377–386.e5. doi:10.1016/j.chom.2017.08.004. ISSN   1931-3128. PMC   5615858 . PMID   28910636.
  5. 1 2 Cullen, Bryan R.; Lomedico, Peter T.; Ju, Grace (1984-01-01). "Transcriptional interference in avian retroviruses—implications for the promoter insertion model of leukaemogenesis". Nature. 307 (5948): 241–245. Bibcode:1984Natur.307..241C. doi:10.1038/307241a0. ISSN   1476-4687. PMID   6363938. S2CID   4277058.
  6. 1 2 Cullen, Bryan R. (1986-09-26). "Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism". Cell. 46 (7): 973–982. doi:10.1016/0092-8674(86)90696-3. ISSN   0092-8674. PMID   3530501. S2CID   20968163.
  7. ↑ Malim, Michael H.; Hauber, Joachim; Le, Shu-Yun; Maizel, Jacob V.; Cullen, Bryan R. (March 1989). "The HIV-1 rev trans -activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA". Nature. 338 (6212): 254–257. Bibcode:1989Natur.338..254M. doi:10.1038/338254a0. ISSN   1476-4687. PMID   2784194. S2CID   4367958.
  8. 1 2 Malim, Michael H.; Böhnlein, Sabine; Hauber, Joachim; Cullen, Bryan R. (1989-07-14). "Functional dissection of the HIV-1 Rev trans-activator—Derivation of a trans-dominant repressor of Rev function". Cell. 58 (1): 205–214. doi:10.1016/0092-8674(89)90416-9. ISSN   0092-8674. PMID   2752419. S2CID   19289070.
  9. 1 2 Malim, Michael H.; Tiley, Laurence S.; McCarn, David F.; Rusche, James R.; Hauber, Joachim; Cullen, Bryan R. (1990-02-23). "HIV-1 structural gene expression requires binding of the rev trans-activator to its RNA target sequence". Cell. 60 (4): 675–683. doi:10.1016/0092-8674(90)90670-A. ISSN   0092-8674. PMID   2406030. S2CID   19377586.
  10. ↑ Weinberg, J. B.; Matthews, T. J.; Cullen, B. R.; Malim, M. H. (1991-12-01). "Productive human immunodeficiency virus type 1 (HIV-1) infection of nonproliferating human monocytes". Journal of Experimental Medicine. 174 (6): 1477–1482. doi: 10.1084/jem.174.6.1477 . ISSN   0022-1007. PMC   2119042 . PMID   1720811.
  11. ↑ Hwang, S. S.; Boyle, T. J.; Lyerly, H. K.; Cullen, B. R. (1992-07-24). "Identification of envelope V3 loop as the major determinant of CD4 neutralization sensitivity of HIV-1". Science. 257 (5069): 535–537. Bibcode:1992Sci...257..535H. doi:10.1126/science.1636088. ISSN   0036-8075. PMID   1636088.
  12. ↑ Zeng, Yan; Wagner, Eric J.; Cullen, Bryan R. (2002-06-01). "Both Natural and Designed Micro RNAs Can Inhibit the Expression of Cognate mRNAs When Expressed in Human Cells". Molecular Cell. 9 (6): 1327–1333. doi: 10.1016/S1097-2765(02)00541-5 . ISSN   1097-2765. PMID   12086629.
  13. ↑ Cai, Xuezhong; Lu, Shihua; Zhang, Zhihong; Gonzalez, Carlos M.; Damania, Blossom; Cullen, Bryan R. (2005-04-12). "Kaposi's sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells". Proceedings of the National Academy of Sciences. 102 (15): 5570–5575. Bibcode:2005PNAS..102.5570C. doi: 10.1073/pnas.0408192102 . ISSN   0027-8424. PMC   556237 . PMID   15800047.
  14. ↑ Umbach, Jennifer Lin; Kramer, Martha F.; Jurak, Igor; Karnowski, Heather W.; Coen, Donald M.; Cullen, Bryan R. (2008). "MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs". Nature. 454 (7205): 780–783. Bibcode:2008Natur.454..780U. doi:10.1038/nature07103. ISSN   1476-4687. PMC   2666538 . PMID   18596690.
  15. ↑ Cai, Xuezhong; Schäfer, Alexandra; Lu, Shihua; Bilello, John P.; Desrosiers, Ronald C.; Edwards, Rachel; Raab-Traub, Nancy; Cullen, Bryan R. (2006-03-24). "Epstein–Barr Virus MicroRNAs Are Evolutionarily Conserved and Differentially Expressed". PLOS Pathogens. 2 (3): e23. doi:10.1371/journal.ppat.0020023. ISSN   1553-7374. PMC   1409806 . PMID   16557291.
  16. ↑ Courtney, David G., Bryan (2017). "Epitranscriptomic enhancement of influenza A virus gene expression and replication". Cell Host & Microbe. 22 (3): 377–386.e5. doi: 10.1016/j.chom.2017.08.004 . PMC   5615858 . PMID   28910636.
  17. ↑ "Duke School of Medicine professor describes mandatory equity training as Maoist political propaganda, refuses to attend". dukechronicle.com. Retrieved 2022-05-26.
  18. ↑ "MGM Bryan Cullen, PhD – Biography". mgm.duke.edu. Retrieved 2020-02-25.
  19. ↑ "MGM FACULTY AWARDS AND HONORS". mgm.duke.edu. Retrieved 2020-02-25.
  20. ↑ "Institute of Advanced Study : IAS Fellows 2006/07: Publications – Durham University". www.dur.ac.uk. Retrieved 2020-02-25.
  21. ↑ "AAAS Members Elected as Fellows". American Association for the Advancement of Science. Retrieved 2020-02-25.
  22. ↑ "73 scientists elected to the American Academy of Microbiology". EurekAlert!. Retrieved 2020-02-25.
  23. ↑ "Global List of Highly Cited Puts Duke in Top Ten". today.duke.edu. Retrieved 2020-02-25.
  24. ↑ SS Hwang; TJ Boyle; HK Lyerly; BR Cullen (1991). "Identification of the envelope V3 loop as the primary determinant of cell tropism in HIV-1". Science. 253 (5015): 71–74. Bibcode:1991Sci...253...71H. doi:10.1126/science.1905842. PMID   1905842.
  25. ↑ Courtney, David G.; Kennedy, Edward M.; Dumm, Rebekah E.; Bogerd, Hal P.; Tsai, Kevin; Heaton, Nicholas S.; Cullen, Bryan R. (2017-09-13). "Epitranscriptomic Enhancement of Influenza A Virus Gene Expression and Replication". Cell Host & Microbe. 22 (3): 377–386.e5. doi: 10.1016/j.chom.2017.08.004 . ISSN   1931-3128. PMC   5615858 . PMID   28910636.
  26. ↑ "PLOS Pathogens: A Peer-Reviewed Open-Access Journal". journals.plos.org. Retrieved 2020-02-25.
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