Mollie Meffert

Mollie Meffert, MD, PhD

Associate Professor

Telephone Number: 410-502-2570

Lab Phone: 410-502-2571

Fax Number: 410-955-5759

Johns Hopkins University

School of Medicine

725 North Wolfe St.

Baltimore, MD 21205

Room: (Lab) 420, 413 Physiology Building

(Office) 421 Physiology

mkm@jhmi.edu

The Regulation of Neuronal Gene Expression in Health and Disease

Our laboratory is particularly interested in how changes in synaptic activity are converted into long-term alterations in the function and connectivity of neurons through the modulation of gene expression. Fundamental questions in gene expression of interest to the lab include:

Why are changes in gene expression required for enduring alterations in synaptic strength, such as during learning, development, or disease?

What pathways exist to generate distinct subcellular changes in gene expression, for example to regulate individual synapse protein composition and input specificity?

How do diverse neuronal stimuli induce specific patterns of gene expression on a synapse, cellular, or network level?

What mechanisms maintain changes in gene expression?

Our laboratory integrates multiple approaches to address the importance of gene expression in information storage at both transcriptional and post-transcriptional levels. We use animal models and techniques of molecular biology, cell biology, biochemistry, high-throughput expression analysis and bioinformatics, virology, histology, confocal imaging, electrophysiology, mouse genetics and behavior. Neuronal gene products of interest include both proteins and non-coding RNAs.

Study of the NF-kB transcription factor provides a good vantage point from which to explore transcriptional regulation in neurons. NF-kB has emerged as a key player in many CNS diseases, including neurodegenerative disorders and cancer. In the healthy CNS, studies from multiple laboratories including our own have demonstrated an evolutionarily conserved requirement for NF-kB in learning and memory. NF-kB is present at synapses and can undergo activation and nuclear translocation from distal processes upon synaptic stimulation. A current focus of our lab is to understand the signaling by the synaptic pool of NF-kB and how NF-kB regulates neuronal functions in both plasticity and disease.

Gene expression in the nervous system can be rapidly altered by control at the level of translation. Changes in translation, like transcription, are also critical for long-term information storage. A second major focus of our laboratory investigates how target specificity is generated in response to neuronal stimuli that regulate protein synthesis. We have discovered that the translating pool of RNA may be controlled through both positive and negative regulation of the biogenesis of mature microRNA from precursor microRNA. Ongoing investigations in our laboratory are aimed at further exploration of the importance of micoRNA biogenesis in determining rapid and specific changes in the neuronal and synaptic proteome and the in vivo roles of these pathways in healthy and dysregulated brain function.

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