Jack Donald Keene, PhD

Professor of Molecular Genetics and Microbiology
James B. Duke Professor of Molecular Genetics and Microbiology
Associate Professor in Medicine
Member of the Duke Cancer Institute
Campus mail 207 Research Drive, 414 Jones Box 3020, Durham, NC 27717
Phone (919) 684-5138
Email address keene001@mc.duke.edu

The Keene Laboratory has a long-term interest in the structure and function of viral and mammalian genomes. Having determined the first genomic sequences for rabies, Ebola, Marburg and vesicular stomatitis virus, and discerned the origins of defective interfering viruses, interests shifted to the cloning of six human genes involved in autoimmune reactivity. This resulted in the identification of numerous autoimmune RRM-type RNA-binding proteins the discovery of the RRM, and the RNA targets to which they bind. The current interests of the lab surround the functions of the human RRM-ELAV/Hu proteins that are bound to a subset of cellular mRNAs involved in growth regulation neuronal plasticiyt and cancer. The laboratory demonstrated that ELAV/Hu proteins bind and regulate the expression of early response gene transcripts such as those encoding the protooncogene and cytokine proteins.

In addition, it was shown that while stabilizing these mRNAs and/or activating their translation, the ELAV/Hu proteins participate in cellular , differentiation and carcinogenesis. More recently, the laboratory has examined dozens of RNA-binding proteins in order to identify large numbers of structurally
and/or functionally related mRNAs that cluster in vivo based upon their binding to these proteins. This has been termed ribonomics because it involves parallel analysis of mRNA subsets en masse based upon their presence in messenger ribonucleoprotein complexes. This new approach to functional genomics is being applied to virus-infected cells, tumors and cells treated with various agents. Ribonomics has led to the identification of mRNA clusters that are posttranscriptionally regulated, and represent the organizational state of genetic information between the genome and the proteome. Dr. Keen has propsed the existence of post-transcriptional operons based upon the association of structurally and functionally-linked mRNAs in vivo.

Education and Training

  • Ph.D., University of Washington, 1974

Publications

Bisogno, LS, and Keene, JD. "Analysis of post-transcriptional regulation during cancer progression using a donor-derived isogenic model of tumorigenesis." Methods (San Diego, Calif.) 126 (August 2017): 193-200.

PMID
28529064
Full Text

Nicholson, CO, Friedersdorf, MB, Bisogno, LS, and Keene, JD. "DO-RIP-seq to quantify RNA binding sites transcriptome-wide." Methods (San Diego, Calif.) 118-119 (April 2017): 16-23.

PMID
27840290
Full Text

Nicholson, CO, Friedersdorf, M, and Keene, JD. "Quantifying RNA binding sites transcriptome-wide using DO-RIP-seq." RNA (New York, N.Y.) 23, no. 1 (January 2017): 32-46.

PMID
27742911
Full Text

Smola, MJ, Christy, TW, Inoue, K, Nicholson, CO, Friedersdorf, M, Keene, JD, Lee, DM, Calabrese, JM, and Weeks, KM. "SHAPE reveals transcript-wide interactions, complex structural domains, and protein interactions across the Xist lncRNA in living cells." Proceedings of the National Academy of Sciences of the United States of America 113, no. 37 (September 2016): 10322-10327.

PMID
27578869
Full Text

Blackinton, JG, and Keene, JD. "Functional coordination and HuR-mediated regulation of mRNA stability during T cell activation." Nucleic acids research 44, no. 1 (January 2016): 426-436.

PMID
26490963
Full Text

Moon, SL, Blackinton, JG, Anderson, JR, Dozier, MK, Dodd, BJT, Keene, JD, Wilusz, CJ, Bradrick, SS, and Wilusz, J. "XRN1 stalling in the 5' UTR of Hepatitis C virus and Bovine Viral Diarrhea virus is associated with dysregulated host mRNA stability." PLoS pathogens 11, no. 3 (March 6, 2015): e1004708-.

PMID
25747802
Full Text

Jiang, H, Xu, L, Wang, Z, Keene, J, and Gu, Z. "Coordinating expression of RNA binding proteins with their mRNA targets." Scientific reports 4 (November 24, 2014): 7175-.

PMID
25417751
Full Text

Blackinton, JG, and Keene, JD. "Post-transcriptional RNA regulons affecting cell cycle and proliferation." Seminars in Cell and Developmental Biology 34 (October 1, 2014): 44-54. (Review)

Full Text

Blackinton, JG, and Keene, JD. "Post-transcriptional RNA regulons affecting cell cycle and proliferation." Seminars in cell & developmental biology 34 (October 2014): 44-54. (Review)

PMID
24882724
Full Text

Payne, TL, Blackinton, J, Frisbee, A, Pickeral, J, Sawant, S, Vandergrift, NA, Freel, SA, Ferrari, G, Keene, JD, and Tomaras, GD. "Transcriptional and posttranscriptional regulation of cytokine gene expression in HIV-1 antigen-specific CD8+ T cells that mediate virus inhibition." Journal of virology 88, no. 17 (September 2014): 9514-9528.

PMID
24899193
Full Text

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