|Faculty and Research
Debra L. Silver, PhD
Duke Institute for Brain Sciences Investigator
Our laboratory uses genetic and cell biological approaches to understand normal development and human disease. Specifically, our studies aim to elucidate the genetic and cell biological mechanisms of stem cells, neural development, and neurodevelopmental disorders.
Precise control of stem cells during development helps dictate the size, structure, and function of different organs of our body, including the adult brain. As evidence of this, genes essential for neural stem cell division are associated with reduced brain size in humans (microcephaly). However, the genes that regulate stem cell division remain poorly understood, as do mechanistic explanations of how aberrant division causes microcephaly. 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 several questions, including the following: How does Magoh regulate neural stem cell division and what are its critical binding partners during brain development? What is the role of mRNA metabolism in neural stem cells? 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.