The teratogenic effects of alcohol consumption on the developing brain can lead to devastating structural, neurologic, and psychologic impairments. The primary goal of this project is to learn how ethanol exerts its effects on brain development by exploring the relationship between ethanol exposure, DNA repair, and cell cycle regulation. Our hypothesis is that ethanol inhibits proliferation of neural stem cells through disruption of genomic replication and repair by cell cycle regulatory molecules. We will approach this issue by investigating the effects of variable ethanol exposure on the cell cycle kinetics, genomic damage, and differential gene transcription of neural stem cells (NSCs). We will also explore the role of the securin gene (PTTG1) in ethanol-induced changes in NSCs. We will study the effects of increased securin expression on NSC proliferation and DNA-repair pathways following ethanol exposure. This research will provide a greater understanding of the mechanisms by which alcohol impairs brain development and cellular division. Such knowledge has widespread applications in fetal alcohol spectrum disorder, or chronic alcoholism.
|Hicks, Steven D; Miller, Michael W (2011) Effects of ethanol on transforming growth factor ?1-dependent and -independent mechanisms of neural stem cell apoptosis. Exp Neurol 229:372-80|
|Hicks, Steven D; Middleton, Frank A; Miller, Michael W (2010) Ethanol-induced methylation of cell cycle genes in neural stem cells. J Neurochem 114:1767-80|