Department of Pathology and Anatomical Sciences
Research Associate Professor
Apoptosis and cell death; Molecular Basis of Disease; Neurobiology
The research in my laboratory has been focused on the effects of chronic ethanol abuse on aging neurons and the effects of ethanol on development of neuronal systems. These investigations are associated with major socioeconomic issues that will become more pronounced with time. For example, alcoholism in the elderly will become more pronounced as the alcohol-drinking baby boomer generation reaches old age. In addition, alcohol consumption during pregnancy remains the number one cause of mental retardation in the western world. In our aging and alcohol studies, extensive investigation of the Purkinje neuron (PN) of the cerebellar cortex have demonstrated that dendritic regression accompanies chronic ethanol consumption in aging Fischer 344 rats. Dendritic regression in PN alters synaptic transmission from the cerebellum, the major brain center for coordination. Further ethanol-induced alteration of regressing dendrites include dilation of the smooth endoplasmic reticulum (SER), a major calcium homeostatic component, and the formation of degenerating structures in dendrites of Purkinje neurons following chronic ethanol consumption in aging rats. These morphologic changes have been recently shown to be accompanied by decreased levels of the SERCA 2b pump which pumps calcium back into the SER following an action potential. Homeostasis between uptake and release of calcium from the SER is essential for cell health as uncontrolled release of calcium results in activation of a myriad of cellular pathways and cell death. Current investigations in the laboratory as focusing on the role ATF6 and caspase 12, both residents of the SER, in the development of ethanol-induced SER stress as a result of chronic ethanol consumption. Future investigations will include other ethanol-induced alterations to calcium homeostatic systems and the role of ethanol-induced alterations in epigenetics in decreases in calcium buffering mechanisms. The fetal alcohol study has focused on the effects of ethanol on the eye and the heart in the zebrafish model. Zebrafish are good models for developmental studies because they are transparent the short developmental period of three days between fertilization and hatching. Early investigations in collaboration with Dr. Richard Rabin established that the zebrafish was sensitive to ethanol and that the sensitivity was dose and strain dependent. Later studies focused on morphological and pharmacological assessment of ethanol-induced alterations to the heart and eye using pharmacologically relevant effects of ethanol. Current plans include focus on determining the mechanisms of ethanol’s actions on retinal ganglion cells and dopaminergic centers in the zebrafish.