Jack Donald Keene, PhD

Professor of Molecular Genetics and Microbiology
James B. Duke Distinguished 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

Ruthig, Victor A., Matthew B. Friedersdorf, Jason A. Garness, Steve C. Munger, Corey Bunce, Jack D. Keene, and Blanche Capel. “The RNA-binding protein DND1 acts sequentially as a negative regulator of pluripotency and a positive regulator of epigenetic modifiers required for germ cell reprogramming.” Development 146, no. 19 (July 25, 2019). https://doi.org/10.1242/dev.175950.

PMID
31253634
Full Text

Bisogno, Laura S., Matthew B. Friedersdorf, and Jack D. Keene. “Ras Post-transcriptionally Enhances a Pre-malignantly Primed EMT to Promote Invasion.” Iscience 4 (June 29, 2018): 97–108. https://doi.org/10.1016/j.isci.2018.05.011.

PMID
30240757
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Wang, Sihyung, Youngmi Jung, Jeongeun Hyun, Matthew Friedersdorf, Seh-Hoon Oh, Jieun Kim, Richard T. Premont, Jack D. Keene, and Anna Mae Diehl. “RNA Binding Proteins Control Transdifferentiation of Hepatic Stellate Cells into Myofibroblasts.” Cell Physiol Biochem 48, no. 3 (2018): 1215–29. https://doi.org/10.1159/000491987.

PMID
30045014
Full Text

Bisogno, Laura S., and Jack D. Keene. “Analysis of post-transcriptional regulation during cancer progression using a donor-derived isogenic model of tumorigenesis.” Methods 126 (August 15, 2017): 193–200. https://doi.org/10.1016/j.ymeth.2017.05.012.

PMID
28529064
Full Text

Nicholson, Cindo O., Matthew B. Friedersdorf, Laura S. Bisogno, and Jack D. Keene. “DO-RIP-seq to quantify RNA binding sites transcriptome-wide.” Methods 118–119 (April 15, 2017): 16–23. https://doi.org/10.1016/j.ymeth.2016.11.004.

PMID
27840290
Full Text

Nicholson, Cindo O., Matthew Friedersdorf, and Jack D. Keene. “Quantifying RNA binding sites transcriptome-wide using DO-RIP-seq.” Rna 23, no. 1 (January 2017): 32–46. https://doi.org/10.1261/rna.058115.116.

PMID
27742911
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Smola, Matthew J., Thomas W. Christy, Kaoru Inoue, Cindo O. Nicholson, Matthew Friedersdorf, Jack D. Keene, David M. Lee, J Mauro Calabrese, and Kevin M. Weeks. “SHAPE reveals transcript-wide interactions, complex structural domains, and protein interactions across the Xist lncRNA in living cells.” Proc Natl Acad Sci U S A 113, no. 37 (September 13, 2016): 10322–27. https://doi.org/10.1073/pnas.1600008113.

PMID
27578869
Full Text

Blackinton, Jeff G., and Jack D. Keene. “Functional coordination and HuR-mediated regulation of mRNA stability during T cell activation.” Nucleic Acids Res 44, no. 1 (January 8, 2016): 426–36. https://doi.org/10.1093/nar/gkv1066.

PMID
26490963
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Moon, Stephanie L., Jeffrey G. Blackinton, John R. Anderson, Mary K. Dozier, Benjamin J. T. Dodd, Jack D. Keene, Carol J. Wilusz, Shelton S. Bradrick, and Jeffrey Wilusz. “XRN1 stalling in the 5' UTR of Hepatitis C virus and Bovine Viral Diarrhea virus is associated with dysregulated host mRNA stability.” Plos Pathog 11, no. 3 (March 2015): e1004708. https://doi.org/10.1371/journal.ppat.1004708.

PMID
25747802
Full Text

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