The goal of the Meffert lab is to gain a mechanistic understanding of how selective gene programs are recruited and maintained to modify the nervous system during development, experience-dependent plasticity, and in injury or disease.  Rather than focusing on single genes, we investigate the upstream processes that allow stimuli to dynamically coordinate regulation of the many genes required to mediate changes in growth and excitation.  We test molecular mechanisms for spatial control of gene programs at the cellular and subcellular level, with a focus on the roles played by non-coding RNA and RNA-binding proteins.  Understanding how genes can be co-regulated post-transcriptionally to produce concerted programs is a fundamental biological question that is also attractive to our laboratory because of its particular relevance for compartmentalized responses in the nervous system, such as forms of synaptic plasticity.

We are highly collaborative and employ multi-disciplinary approaches of molecular diagnostics, biochemistry, high resolution cellular imaging, mouse genetics and behavior, and data science.  Discovery-based sequencing strategies have been developed to reveal in vivo small RNA targets through the production of small RNA: target chimeric molecules.  The Meffert lab leverages an understanding of basic gene control mechanisms to illuminate potential therapeutic targets in both nerve injury and the development of cognitive disabilities, including Autism Spectrum Disorders such as Fragile X Syndrome, in which disruption of the growth and function of synaptic connections is a central component.  Ongoing studies use mouse models and human samples to investigate how translation, miRNA biogenesis and miRNA:target interactions, may be pathologically regulated to produce the aberrant protein synthesis and phenotypes associated with autism.