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Debra Silver

Assistant Professor
Molecular Genetics and Microbiology
(919) 668-7909
Research Interest: 
Developmental biology
Research Summary: 
Genetic mechanisms of stem cells and neural development
Research Description: 

Our laboratory is interested in mechanisms that underlie normal development and human disease. Specifically our studies aim to elucidate mechanisms of stem cells and brain development, as well as the causes of neurodevelopmental disorders. Precise control of stem cells during development helps dictate the size, structure, and function of different organs of our body. The factors that regulate stem cells remain poorly understood, and we lack a good mechanistic explanation of how aberrant stem cell division causes diseases such as microcephly (in which brain size is reduced). Our goal is to help fill this void by uncovering new genes important for stem cell division and brain development.

In previous studies utilizing a forward genetic screen in mice, we identified a requirement for Magoh, a component of an RNA binding complex, for proper brain size, asymmetric cell division, genomic stability, and neural stem cell function. Future projects in our laboratory will build upon these findings to ask: How does Magoh regulate stem cell division; what are its critical binding partners during brain development; does ithave a conserved role in other stem cells? What is the role of mRNA localization and metabolism during stem cell division? What additional genes regulate these processes and influence neurodevelopmental diseases such as microcephaly?

Our approach employs a repertoire of genetic and cell biological tools including mouse genetics, cell culture, microscopy, biochemistry, and genomics. Using this combination of in vivo and in vitro studies allows us to gain mechanistic insights both at a molecular and organismal level. Our long-term objective is that these approaches help broaden our fundamental understanding of both basic and translational problems ranging from how cells divide to the etiology of developmental diseases and cancers.

Dynamic mRNA Transport and Local Translation in Radial Glial Progenitors of the Developing Brain.
Pilaz LJ, Lennox AL, Rouanet JP, Silver DL.
Curr Biol. 2016. :.

Haploinsufficiency for Core Exon Junction Complex Components Disrupts Embryonic Neurogenesis and Causes p53-Mediated Microcephaly.
Mao H, McMahon JJ, Tsai YH, Wang Z, Silver DL.
PLoS Genet. 2016. 12:e1006282.

Prolonged Mitosis of Neural Progenitors Alters Cell Fate in the Developing Brain.
Pilaz LJ, McMahon JJ, Miller EE, Lennox AL, Suzuki A, Salmon E, Silver DL.
Neuron. 2016. 89:83-99.

Rbm8a haploinsufficiency disrupts embryonic cortical development resulting in microcephaly.
Mao H, Pilaz LJ, McMahon JJ, Golzio C, Wu D, Shi L, Katsanis N, Silver DL.
J Neurosci. 2015. 35:7003-18.

Human-chimpanzee differences in a FZD8 enhancer alter cell-cycle dynamics in the developing neocortex.
Boyd JL, Skove SL, Rouanet JP, Pilaz LJ, Bepler T, Gordân R, Wray GA, Silver DL.
Curr Biol. 2015. 25:772-9.