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Dr. Debra Silver, Ph.D


Assistant Professor
Duke University School of Medicine
Durham , NC, USA

Hangout Title: From development to evolution: Common dynamic mechanisms shaping our brains and underlying disease.
Hangout Schedule : Jan 25th- 7.30 am CST, 8.30 am EST, 5.30 am PST, 7 pm IST

debra

Our laboratory studies embryonic brain development, focusing on the process of neurogenesis.  During neurogenesis of the cerebral cortex, neural progenitors produce neurons.  This process helps dictate the size, structure, and function of the adult brain. Moreover, aberrant neurogenesis can cause neurodevelopmental disorders such as microcephaly (reduced brain size associated with intellectual disability) and autism spectrum disorder. Despite the fundamental clinical relevance of neurogenesis, the mechanisms controlling this process remain poorly understood. Our goal is to help fill this void by elucidating genetic and cellular regulation of neural progenitors in the developing brain.

A major research direction of our lab is to understand mechanisms controlling brain size. We are especially interested in how post-transcriptional regulation influences dynamic neural progenitor behavior and function.  The RNA binding proteins studied are associated with neurodevelopmental pathologies including brain malformations.  A second focus of our research is to understand how regulatory sequences, termed enhancers, contribute to unique features of the human brain by modulating neural progenitor proliferation. The lab employs a repertoire of genetic and cell biological tools including mouse genetics, ex vivo and in vitro live imaging, genomics, and proteomics. Using multidisciplinary approaches give us mechanistic insights at molecular, cellular, and tissue levels.  Our long-term objective is to help broaden our fundamental understanding of how the brain is built, how stem cells behave, and the etiology of developmental diseases.

Education and Training
  • Tufts University, B.S. 1993
  • Johns Hopkins University, Ph.D. 2003
  • National Institutes of Health, Postdoctoral Fellowship, National Human Genome Research Institute
  • Associated Faculty Labs
  • Silver Lab

Selected Grants and Awards
  • RNA localization in neural stem cells during cortical development
  • Zika virus infection of neural stem cells to model pathogen-induced microcephaly
  • Mechanisms of neural progenitor division in the developing brain
  • Dissecting the role of the exon junction complex in embryonic corticogenesis
  • Serial Block Face Scanning Electron Microscope

Training Program in Developmental and Stem Cell Biology
  • Analysis of the Exon Junction Complex in Neural Development and Microcephaly
  • Department Affiliation
  • Department of Molecular Genetics and Microbiology


Publications

Mao, H, Brown, HE, and Silver, DL. "Mouse models of Casc3 reveal developmental functions distinct from other components of the exon junction complex." RNA (New York, N.Y.) 23, no. 1 (January 2017): 23-31.
McMahon, JJ, Miller, EE, and Silver, DL. "The exon junction complex in neural development and neurodevelopmental disease." International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 55 (December 2016): 117-123. (Review)
Pilaz, LJ, Lennox, AL, Rouanet, JP, and Silver, DL. "Dynamic mRNA Transport and Local Translation in Radial Glial Progenitors of the Developing Brain." Current biology : CB 26, no. 24 (December 2016): 3383-3392.
Mao, H, McMahon, JJ, Tsai, YH, Wang, Z, and Silver, DL. "Haploinsufficiency for Core Exon Junction Complex Components Disrupts Embryonic Neurogenesis and Causes p53-Mediated Microcephaly." PLoS genetics 12, no. 9 (September 12, 2016): e1006282-.
Silver, DL. "Genomic divergence and brain evolution: How regulatory DNA influences development of the cerebral cortex." BioEssays : news and reviews in molecular, cellular and developmental biology 38, no. 2 (February 2016): 162-171.
Pilaz, L-J, McMahon, JJ, Miller, EE, Lennox, AL, Suzuki, A, Salmon, E, and Silver, DL. "Prolonged Mitosis of Neural Progenitors Alters Cell Fate in the Developing Brain." NEURON 89, no. 1 (January 6, 2016): 83-99.
Singh, SK, Stogsdill, JA, Pulimood, NS, Dingsdale, H, Kim, YH, Pilaz, LJ, Kim, IH, Manhaes, AC, Rodrigues, WS, Pamukcu, A, Enustun, E, Ertuz, Z, Scheiffele, P, Soderling, SH, Silver, DL, Ji, RR, Medina, AE, and Eroglu, C. "Astrocytes Assemble Thalamocortical Synapses by Bridging NRX1α and NL1 via Hevin." Cell 164, no. 1-2 (January 2016): 183-196.
Pilaz, LJ, and Silver, DL. "Post-transcriptional regulation in corticogenesis: how RNA-binding proteins help build the brain." Wiley interdisciplinary reviews. RNA 6, no. 5 (September 2015): 501-515. (Review)
Mao, H, Pilaz, LJ, McMahon, JJ, Golzio, C, Wu, D, Shi, L, Katsanis, N, and Silver, DL. "Rbm8a haploinsufficiency disrupts embryonic cortical development resulting in microcephaly." The Journal of neuroscience : the official journal of the Society for Neuroscience 35, no. 18 (May 2015): 7003-7018.
Boyd, JL, Skove, SL, Rouanet, JP, Pilaz, LJ, Bepler, T, Gordân, R, Wray, GA, and Silver, DL. "Human-chimpanzee differences in a FZD8 enhancer alter cell-cycle dynamics in the developing neocortex." Current biology : CB 25, no. 6 (March 2015): 772-779.