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Dr. Mollie Meffert is an associate professor of biological chemistry and neuroscience at the Johns Hopkins University School of Medicine. Her research focuses on the regulation of neuronal gene expression in health and disease.
Dr. Meffert received her undergraduate degree from Stanford University. She also earned her MD/Ph.D in neuroscience from Stanford University. She completed a postdoctoral fellowship at California Institute of Technology. Dr. Meffert joined the Johns Hopkins faculty in 2004.
The Meffert lab studies mechanisms underlying enduring changes in brain function. We are interested in understanding how programs of gene expression are coordinated and maintained to produce changes in synaptic, neuronal, and cognitive function. Rather than concentrating on single genes, our research is particularly focused on understanding the upstream processes that allow neuronal stimuli to synchronously orchestrate both up and down-regulation of the many genes required to mediate changes in growth and excitation.
Our laboratory recently elucidated a mechanism responsible for pro-growth programs of protein synthesis 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. Let-7 ‘tumor 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, with examples being AMPA receptor subunits (GluA1), CaMKIIa, Homer, BDNF, and TrkB. Ongoing investigations in our laboratory are aimed at further exploration of the importance of miRNA 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.
Dr. Meffert’s work has been recognized with a number of awards including the March of Dimes research scholar, a Simons Foundation Autism Research Initiative award, the Alfred P. Sloan Research Fellow Award, and the Sontag Foundation Distinguished Scientist Award.
California Inst. of Technology, Pasadena, CA
Exploring how gene expression determines synaptic function
Mollie Meffert is a neuroscientist whose laboratory investigates how gene programs modify the brain during experience and disease. The Meffert Lab uses mouse genetics and animal models, molecular and biochemical strategies, expression arrays and bioinformatics, virology, histology, live confocal imaging and electrophysiology to explore the importance of gene expression in information storage at both transcriptional and post-transcriptional levels.
The Meffert 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. How do gene programs modify the brain during experience and disease?
The laboratory integrates multiple approaches to address the importance of gene expression in information storage at both transcriptional and post-transcriptional levels. They 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.
Lab Website: Mollie Meffert Lab
Erica C. Dresselhaus, Matthew C. Boersma, and Mollie K. Meffert, (2018), Targeting of NF-kB to dendritic spines is required for synaptic signaling and spine development. J.Neurosci., 8(17); 4093-4103. PMID 29555853.
Laurel M. Oldach, Kirill Gorshkov,William T. Mills, Jin Zhang*, and Mollie Meffert* (2018), A biosensor for MAPK-dependent Lin28 signaling. Molecular Biology of the Cell, 29(10), 1157-1167. PMID29540527.
Alexandra M Amen, Claudia R. Ruiz, Jay Shi, Megha Subramanian, Daniel Pham, and Mollie K. Meffert, (2017) A rapid induction mechanism for Lin28a in trophic responses. Molecular Cell, 65 (3); 490 - 503.
Subramanian M, Timmerman CK, Schwartz JL, Pham DL, Meffert MK. Characterizing autism spectrum disorders by key biochemical pathways. Front Neurosci. 2015 Sep 24;9:313. doi: 10.3389/fnins.2015.00313. eCollection 2015.
Yu-Wen A. Huang*, Claudia R. Ruiz*, E.C.H. Eyler*, Kathie Lin, and Mollie K. Meffert. "Dual regulation of miRNA biogenesis generates target specificity in neurotrophin-induced protein synthesis." Cell, 148(5); 933-946. 2012.
Graduate Program in Biological Chemistry
Biochemistry, Cellular and Molecular Biology Graduate Program
Neuroscience Graduate Program
XDBio cross-disciplinary graduate training program
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