A) A primary focus of our work is to decipher the molecular mechanisms governing the exciting field of RNA transport/localization. This process is of fundamental importance in development and differentiation, and its disruption can result in birth defects, infertility and certain nerve-muscle disorders. We take a multidisciplinary approach involving techniques from molecular biology, biochemistry, cell biology and genetics. Extensive use is made of synthetic RNA transcripts, cellular extracts and the battery of techniques used to investigate RNA-protein interactions in other steps of RNA biogenesis. Our model systems include Drosophila development and human neuromuscular disease. Efforts have included: 1) identifying composite discrete cis-acting RNA localization signals; 2) employing these signals to characterize/isolate localization factors which recognize them and 3) examining the regulatory link between RNA localization and other post-transcriptional processes. Efforts also explore the role of key riboregulators (microRNAs) in several of these post-transcriptional processes. Our investigation will facilitate definition of the fundamental principals underlying the important process of mRNA trafficking and provide insights into the creation of cell polarity. Additionally, it will elucidate how the process can go awry, leading to developmental defects and disease.

B) Recently, we identified the first human disease likely caused by RNA mislocalization. This opens a plethora of novel research avenues and created a second avenue of active lab research into human disease etiology and progression. In complimentary analyses, we are also embarking on a study to understand the molecular basis of pregnancy-induced autoimmunity with nerve and muscle targets. In both projects, our findings raise the possibility of totally new means of gene therapy.