Overview
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.
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.
Current Appointments & Affiliations
James B. Duke Distinguished Professor of Molecular Genetics and Microbiology
·
1997 - Present
Molecular Genetics and Microbiology,
Basic Science Departments
Professor of Molecular Genetics and Microbiology
·
1989 - Present
Molecular Genetics and Microbiology,
Basic Science Departments
Associate Professor in Medicine
·
2020 - Present
Medicine, Rheumatology and Immunology,
Medicine
Member of the Duke Cancer Institute
·
1979 - Present
Duke Cancer Institute,
Institutes and Centers
Recent Publications
The RNA binding protein DND1 is elevated in a subpopulation of pro-spermatogonia and targets chromatin modifiers and translational machinery during late gestation.
Journal Article PLoS Genet · March 2023 DND1 is essential to maintain germ cell identity. Loss of Dnd1 function results in germ cell differentiation to teratomas in some inbred strains of mice or to somatic fates in zebrafish. Using our knock-in mouse line in which a functional fusion protein be ... Full text Link to item CiteA transgenic DND1GFP fusion allele reports in vivo expression and RNA-binding targets in undifferentiated mouse germ cells†.
Journal Article Biol Reprod · April 1, 2021 In vertebrates, the RNA-binding protein (RBP) dead end 1 (DND1) is essential for primordial germ cell (PGC) survival and maintenance of cell identity. In multiple species, Dnd1 loss or mutation leads to severe PGC loss soon after specification or, in some ... Full text Link to item CiteTHE RNA BINDING PROTEIN ZFP36L1 MAINTAINS HEPATOCYTE MATURITY IN HEALTHY ADULT LIVER
Conference HEPATOLOGY · 2020 CiteRecent Grants
Hematology & Transfusion Medicine (T32)
Inst. Training Prgm or CMEPreceptor · Awarded by National Institutes of Health · 1975 - 2026Genetic and Genomics Training Grant
Inst. Training Prgm or CMEMentor · Awarded by National Institutes of Health · 2020 - 2025Bioinformatics and Computational Biology Training Program
Inst. Training Prgm or CMEMentor · Awarded by National Institutes of Health · 2005 - 2021View All Grants
Education, Training & Certifications
University of Washington ·
1974
Ph.D.