Recovery of function after brain insult such as Alzheimer's disease, stroke or trauma. The lab works on dendritic spines, small protrusions from dendritic shafts on which synaptic contacts are made with other neurons. Spines play a major role in providing a substrate for memory and learning and in allowing recovery from brain damage. The lab is currently examining the role of histone modification in spine growth-related and cell death related events. Special emphasis is placed on communication between spine and nucleus and consequent regulation of gene expression.
Karen Dietz is a graduate student who is growing slices of hippocampus, a brain region involved in learning and memory, in culture. These slices may then be subjected to various treatments such as hypoxia, lesions, receptor blockade and the insertion of specific genes to determine the factors, including the expression of specific genes, that make spines come and go. Karen has found that local synthesis of actin, a key protein that forms the backbone of the spine, is associated with the production of an increased number of spines. Increased spine number would foster the development of new circuitry that could compensate for damage-induced losses. The techniques Karen uses include immunocytochemistry, Western blotting, PCR, laser confocal microscopy and live imaging of neurons in culture during which spines can be observed as they move about, develop or retract. These studies will give us a better understanding of how the brain reacts to damage and how recovery from that damage might be facilitated.
Mike Darcy is a graduate student who is focusing on mechanisms by which dendritic spines may communicate with the nucleus to turn genes on or off. This type of communication is likely involved with signaling neurons that they should or should not commit suicide depending on how heavily they are used in a given circuit. These studies are particularly germane to Alzheimer's disease in which neurons become disconnected from circuits (for unknown reasons) and then commit suicide (apoptosis). Mike has found that histones regulating gene expression are dramatically modified during brain damage and is experimenting with drug treatments that may reverse or prevent that damage. The techniques he uses include PCR, Western blotting, laser confocal microscopy, immunocytochemistry and the chromatin histone immunoprecipitation assay. These studies will show how specific genes are regulated as spines develop or retract and will explore relationships between spine activity and gene expression.
Katie Cavnar is a senior biological scientist who keeps the lab running and participates in the experiments. In addition to all of the work described above, Katie works on the light and electron microscopic localization of spine-related proteins and plays a major role in experimental design and execution.