Diane M. Papazian, Ph.D.

Research

Our work focuses on voltage-gated K channels. These channels are integral membrane proteins that open a pore for K in response to depolarization of the transmembrane voltage. Functionally, K channels are important in controlling the excitability of nerve and muscle. In our current research projects, we are investigating how voltage controls the activity of K channel proteins and how mutations in Kv3.3 channels cause the human disease, Spinocerebellar Ataxia Type 13 (SCA13). SCA13 is characterized by substantial loss of cerebellar neurons and motor problems. SCA13 exists in two allelic forms. One form emerges in infancy and disrupts neurodevelopment, whereas the other form is a progressive neurodegenerative disease of aging. Because the function of Kv3.3 channels in the cerebellum is well understood, SCA13 provides an outstanding opportunity to dissect specific pathogenic mechanisms to determine how two different mutations in a voltage-gated K channel gene disrupt cerebellar development in one case or lead to progressive cerebellar degeneration in the other. As part of this project, we are making a zebrafish model of SCA13 to study the effects of disease-causing mutations on neuronal development and function. Zebrafish is an ideal system for this work because multiple levels of analysis from molecular to behavioral are readily accessible. We are a multi-disciplinary lab using the techniques of biochemistry, electrophysiology, molecular biology, cell biology, and genetics to address our questions of interest.