Johns Hopkins School of Medicine

The Regulation of Neuronal Gene Expression in Health and Disease

The Meffert lab investigates mechanisms underlying enduring change in mammalian nervous system function in health and disease. We are interested in how cells in the nervous system make decisions to turn genes on or off, and how those decisions are remembered in processes such as development or plasticity, and in injury or disease. The goal of the Meffert lab is to gain a mechanistic understanding of how selective gene programs are recruited and maintained to alter synaptic, neuronal, and cognitive function. Rather than focusing on single genes, we investigate the upstream processes that allow coordinate regulation of many genes to achieve biological impact. Cell-specific and subcellularly localized posttranscriptional control by RNA-binding proteins and noncoding RNAs is an ongoing focus.

Our laboratory elucidated a post-transcriptional mechanism capable of organizing pro-growth gene programs in which activity-dependent regulation of microRNA (miRNA) production governs the selection of gene targets for protein synthesis. An RNA-binding protein, Lin28, is one activity-responsive factor that promotes pro-growth protein synthesis by downregulating only select miRNAs (e.g. the family of let-7 ‘growth-suppressor’ miRNAs), which repress pro-growth genes. In neurons, pro-growth mRNA targets of the let-7 miRNAs include mRNA for proteins involved in excitatory synaptic function, as well as growth, metabolism, and repair. In recent work, we develop discovery-based sequencing strategies to reveal in vivo small RNA targets through the production of small RNA:target chimeric molecules.

Dr. Meffert’s work has been recognized with awards including the: March of Dimes research scholar, Simons Foundation Autism Research Initiative award, PLU Rho Award, Alfred P. Sloan Research Fellow Award, Hamilton Smith Award for Innovative Science, and The Sontag Foundation Distinguished Scientist and Distinguished Alumni Awards.  Dr. Meffert and her laboratory are the current recipients of the Eric C. Aker Award Endowment through the Braude Foundation.

Expertise

Dr. Meffert received her undergraduate degree (BS) from Stanford University. She earned her MD/PhD in neuroscience from Stanford University School of Medicine and completed a postdoctoral fellowship at California Institute of Technology with Dr. David Baltimore.

Areas of research expertise in Dr. Meffert’s laboratory include molecular neuroscience, RNA biology, and gene expression. Her laboratory uses tools of molecular diagnostics, biochemistry, computational biology, quantitative imaging, and mouse and human genetic models of neurodevelopment and neural disease