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Mollie K. Meffert Portrait

Mollie K. Meffert
Associate Professor of Biological Chemistry
Johns Hopkins University School of Medicine

413 Physiology Building
725 N. Wolfe St
Baltimore, MD21205
Office Phone: 410-502-2570
Lab Phone: 410-502-2571
Fax: 410-955-5759
Email: mkm@jhmi.edu
Lab Web Site

Click Here for PDF of CV

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-κB transcription factor provides a good vantage point from which to explore transcriptional regulation in neurons.  NF-κB 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-κB in learning and memory.  NF-κB 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-κB and how NF-κB 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.
 

For images of our work 

Recent links to our work: 
Neuroscience Innovations   

Videos showing increased mRNA repression (RNA-processing bodies) in live neurons responding to BDNF:
Messenger RNA accumulates in a neuron
BDNF-treated neuron

Recent Publications

Huang*Y-WA, Ruiz*CR, Eyler ECH*, Lin K, and Meffert MK (2012). Dual regulation of miRNA biogenesis generates target specificity in neurotrophin-induced protein synthesis.  Cell, 148(5); 933-946.
PubMed Reference 

Boersma* MC, Dresselhaus*EC, De Biase LM, Mihalas AB, Bergles DE, and Meffert MK (2011), A requirement for NF-kB in developmental and plasticity-associated synaptogenesis.  J.Neurosci., 31; 5414-5425.
PubMed Reference
 

Shrum CK, Defrancisco D, and Meffert MK. (2009) Stimulated nuclear translocation of NF-kB and shuttling differentially depend on dynein and the dynactin complex. PNAS, 106; 2647-2652.
PubMed Reference
 

Boersma MC and Meffert MK (2008) Novel roles for the NF-kB signaling pathway in regulating neuronal function.  Science Signaling 1, pe7.
PubMed Reference
 

Shrum CK and Meffert MK (2008). The NF- kB Family in Learning and Memory. In J. David Sweatt(Ed.), Molecular Mechanisms of Memory. Vol. [4] of Learning and Memory: A Comprehensive Reference (J.Byrne Editor), pp. [567-586] Oxford: Elsevier 

Mattson MP and Meffert MK (2006). Roles for NF-kB in nerve cell survival, plasticity, and disease. Cell Death and Differentiation 13, 852-60.
PubMed Reference​ 

Meffert MK and Baltimore D (2005). Physiological functions for brain NF-kB.  Trends in Neurosciences 28, 37-43.
PubMed Reference 

Meffert MK, Chang JM, Wiltgen BJ, Fanselow MS, Baltimore D (2003).  NF-kB functions in synaptic signaling and behavior. Nature Neuroscience 6, 1072 - 1078.
PubMed Reference 

Meffert MK, Calakos NC, Scheller RH, Schulman H (1996). Nitric oxide modulates synaptic vesicle docking / fusion reactions. Neuron 16, 1229-1236.
PubMed Reference 

Meffert*MK, Haley*JE, Schuman EM, Schulman H, and Madison DV (1994). Inhibition of hippocampal heme oxygenase, nitric oxide synthase and long-term potentiation by metalloporphyrins. Neuron 13, 1225-1233.
PubMed Reference 

Meffert MK, Premack BA, and Schulman H (1994). Nitric oxide stimulates calcium-independent synaptic vesicle release. Neuron 12, 1235-1244.
PubMed Reference 

Schuman EM, Meffert MK, Schulman H, Madison DV (1994). An ADP-Ribosyltransferase as a Target for Nitric Oxide Action in Long-Term Potentiation. Proceedings of the National Academy of Sciences 91, 11958-11962.
PubMed Reference 


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