Keene studies the regulation of RNA and the mechanisms of RNA-protein interactions. In his work on molecular genetics, he and his coworkers have examined the role of DNA and RNA-binding proteins (RBPs) in the pathogenesis of autoimmunity. and for
Ebola virus and
Marburg virus from the broader group of negative-strand RNA viruses (NSRV). He identified the origins of
defective interfering particles of negative-strand RNA viruses. Through combinatorial studies of viral and bacterial systems, he has identified targets for novel pharmacological studies. In 1987, Query and Keene first identified a B-cell
epitope within the
U1-70K protein. Keene isolated the first human autoimmune antigen and elucidated its autoimmune epitopes, the parts of an antigen to which antibodies in the immune system can bind. Keene's lab has identified functions of the ELAV/Hu posttranscriptional regulators HuB, HuC and HuD and their roles and that of HuR in processes of growth, proliferation, differentiation, and immune response. The study of RNA-binding proteins such as HuR and the determination of the binding of specific sequences have informed Keene's later post-transcription theory and his coordination theory of RNA operons. In 2001–2002, Keene formalized the posttranscriptional operon and regulon (PTRO) model for global gene regulation. By 2007, Keene proposed the RNA regulon hypothesis, "that mRNAs encoded by functionally related genes may be coordinately regulated as posttranscriptional RNA regulons by specific mRNP processing machineries". The purpose of the RNA regulon model was to better understand
post-transcriptional regulation, to answer the question "How does the cell coordinate metabolism and regulation of mRNAs encoding proteins in the same biological process so that the proteins can be coordinately produced?" ==Awards and honors==