Susan M. Smith, PhD
Institute Deputy Director for Science,
Dickson Foundation – Harris Teeter Distinguished Professor of Nutrition
Dr. Smith’s laboratory studies the molecular mechanisms by which dietary components affect prenatal development. Current work largely focuses upon ethanol and how it causes fetal alcohol syndrome. We are interested in how alcohol damages the embryo and fetus, and in the environmental and genetic factors that attenuate or heighten alcohols neurotoxicity.
First described in 1968, Fetal Alcohol Spectrum Disorders (FASD) remain a leading known cause of neurodevelopmental impairment in the U.S. Our work examines the molecular mechanism by which alcohol causes the specific neurobehavioral and craniofacial dysmorphologies that typify FASD. Our research has identified much of the intracellular signaling pathway initiated by ethanol to trigger the apoptotic elimination of craniofacial precursors, a population known as the neural crest.
These signals involve the G protein / inositide phosphate-mediated release of intracellular calcium stores, which in turn activate calcium signals including CaMKII, and the subsequent loss of nuclear ?-catenin, which is an important trophic factor for neural crest survival. We have identified two closely related chick embryo strains whose neural crest populations differ greatly in their sensitivity to ethanol-induced apoptosis. We have initiated molecular analysis to identify gene sequences that may confer sensitivity or resistance to ethanols neurotoxicity. We have also become very interested in maternal nutritional factors that modulate fetal sensitivity to alcohol. We have recently shown that a subclinical maternal iron inadequacy greatly exacerbates alcohols damage to the cerebellum and to cerebellum-dependent learning.