Jack Donald Keene

About

Jack Donald Keene is the James B. Duke Distinguished Professor of Molecular Genetics and Microbiology, as well as a Professor of Molecular Genetics and Microbiology and an Associate Professor in Medicine at Duke University. He is a member of the Duke Cancer Institute. His research has a long-term focus on the structures and functions of viral and mammalian genomes. In the early 1980s, his lab determined the first genomic sequences for rabies, Ebola, and VS viruses, and studied small noncoding RNAs called leader RNAs generated by these viruses. His work revealed that leader RNAs of VSV and rabies bind to a cellular host RNA-binding protein called La, which assists virus infectivity by blocking access of the RIG-I protein to the leader RNA, thereby influencing the activation of the type I interferon response. Keene's lab derived cDNA clones of the La RBP using sera from patients with autoimmune diseases such as Lupus and Sjogren’s syndrome, leading to the development of the first recombinant diagnostic test for autoantibodies. He identified a common RNA-binding motif, the RNA Recognition Motif (RRM), which forms the core of a functional RNA-binding domain. Since 1991, his research has focused on the functions of human RRM-ELAV/Hu RBPs, demonstrating their role in binding AU-rich sequences and increasing the stability and translation of their mRNA targets. More recently, his lab devised methods to identify cellular mRNAs and microRNAs associated with RNA-binding proteins, a…

Research topics

• Biology
• Genetics
• Cell biology
• Molecular biology

Selected publications

• SHAPE reveals transcript-wide interactions, complex structural domains, and protein interactions across the <i>Xist</i> lncRNA in living cells

  Proceedings of the National Academy of Sciences · 2016-08-30 · 244 citations

  article

  The 18-kb Xist long noncoding RNA (lncRNA) is essential for X-chromosome inactivation during female eutherian mammalian development. Global structural architecture, cell-induced conformational changes, and protein-RNA interactions within Xist are poorly understood. We used selective 2'-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP) to examine these features of Xist at single-nucleotide resolution both in living cells and ex vivo. The Xist RNA forms complex w…

  PublisherDOI

• Post-transcriptional RNA regulons affecting cell cycle and proliferation

  Seminars in Cell and Developmental Biology · 2014-06-02 · 99 citations

  reviewOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• XRN1 Stalling in the 5’ UTR of Hepatitis C Virus and Bovine Viral Diarrhea Virus Is Associated with Dysregulated Host mRNA Stability

  PLoS Pathogens · 2015-03-06 · 78 citations

  articleOpen access

  We demonstrate that both Hepatitis C virus (HCV) and Bovine Viral Diarrhea virus (BVDV) contain regions in their 5' UTRs that stall and repress the enzymatic activity of the cellular 5'-3' exoribonuclease XRN1, resulting in dramatic changes in the stability of cellular mRNAs. We used biochemical assays, virus infections, and transfection of the HCV and BVDV 5' untranslated regions in the absence of other viral gene products to directly demonstrate the existence and mechanism of this novel host-v…

  PublisherOA PDFDOI

• RNA regulons in cancer and inflammation

  Current Opinion in Genetics & Development · 2017-11-23 · 65 citations

  reviewOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Quantifying RNA binding sites transcriptome-wide using DO-RIP-seq

  RNA · 2016-10-14 · 49 citations

  articleOpen accessSenior author

  RNA-binding proteins (RBPs) and noncoding RNAs orchestrate post-transcriptional processes through the recognition of specific sites on targeted transcripts. Thus, understanding the connection between binding to specific sites and active regulation of the whole transcript is essential. Many immunoprecipitation techniques have been developed that identify either whole transcripts or binding sites of RBPs on each transcript using cell lysates. However, none of these methods simultaneously measures…

  PublisherOA PDFDOI

Recent grants

• RNA Operons in Coordinated Gene Expression and Horizontal Transfer

  NSF · $930k · 2009–2014

• NIH Grant R01CA079907

  NIH · $1.5M · 2006

• NIH Grant R01AI016099

  NIH · $1.4M · 1993

Frequent coauthors

• Lucille D. Fresco

  Harvard University

  88 shared

• Charles C. Query

  Albert Einstein College of Medicine

  73 shared

• Jeffrey Wilusz

  Colorado State University

  68 shared

• Michael G. Kurilla

  59 shared

• Matthew Friedersdorf

  NeuroMetrix (United States)

  47 shared

• Daniel J. Kenan

  Arkana Laboratories

  46 shared

• Scott A. Tenenbaum

  41 shared

• David S. Pisetsky

  Durham VA Medical Center

  40 shared

Labs

• Keene LabPI

Similar researchers at Duke University

• Douglas Alan Marchukh-110
• Hiroaki Matsunamih-86
• Thomas Douglas Petesh-78