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 in the mid 1980’s to the cloning of six human genes involved in autoimmune diseases. These autoimmune protein genes encoded RRM-type RNA-binding proteins and led to the discovery of the RNA Recognition Motif (RRM) and the elucidation of RNA targets to which they bind. For many years, the lab has focused on the functions of human RRM-ELAV/Hu proteins that they found can bind and regulate subsets of cellular mRNAs involved in growth regulation, neuronal plasticity, immune regulation and cancer. More recently, the Keene lab devised methods to identify structurally and functionally related mRNAs and microRNAs that cluster together based upon their association with specific RNA-binding proteins. This general approach has been termed ribonomics because it uses microarrays and parallel analysis of mRNA and microRNA subsets en masse based upon their association with ribonucleoprotein complexes. These studies have revealed mRNA clusters, including those of the Wnt Pathway, that are post-transcriptionally regulated, and represent the organizational state of genetic information between the genome and the proteome in eukaryotic cells. Based on these findings, Dr. Keene proposed the concept of Post-Transcriptional RNA Operons (PTRO) based upon the combinatorial regulation of mRNAs from transcription to translation by trans-acting RNA-binding proteins and microRNAs that coordinate the production of functionally related proteins. The PTRO model can reveal targets for globally modulating gene expression networks and has a variety of therapeutic implications.