Diane M. Papazian, Ph.D.

Work Address:
Los Angeles, CA 90095 CHS
Los Angeles, CA 90095

Professor, Physiology
Member, Brain Research Institute, Cell & Developmental Biology GPB Home Area, Molecular, Cellular & Integrative Physiology GPB Home Area, Neuroscience GPB Home Area
Research Interests
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 diisease 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.

Professor Papazian received her B.S. in Chemistry from the University of Michigan in 1977. She received her Ph.D. in Biological Chemistry from Harvard University in 1983. She was a postdoctoral fellow in Dr. Lily Jan's laboratory at the University of California at San Francisco from 1983-1989. She joined the UCLA faculty in 1989 and now holds the rank of Professor in the Department of Physiology

Issa FA, Mazzochi C, Mock AF, and Papazian DM Spinocerebellar ataxia type 13 mutant potassium channel alters neuronal excitability and causes locomotor deficits in zebrafish. J. Neurosci 2011; 31: 6831-6841.
Issa FA, O?Brien G, Kettunen P, Sagasti A, Glanzman DL, and Papazian DM Neural circuit activity in freely-behaving zebrafish (Danio rerio). J. Exp. Biol 2011; 214: 1028-1038.
Mock AF, Richardson JL, Hsieh JY, Rinetti G, and Papazian DM Functional effects of spinocerebellar ataxia type 13 mutations are conserved in zebrafish Kv3.3. BMC Neurosci 2010; 11: 99.
Figueroa, K.P., Minassian, N.A., Stevanin G., Waters, M., Garibyan, V., Bürk, K., Brice, A., Dürr, A., Papazian, D.M., and Pulst, S.M. KCNC3: Phenotype, mutations, channel biophysics—a study of 260 familial ataxia patients. . Hum. Mutat 2009; 31: 191-196.
Lin MA, Abramson J, and Papazian DM Transfer of ion binding site from ether-à-go-go to Shaker: Mg2+ binds to resting state to modulate channel opening. J. Gen. Physiol 2010; 135: 415-431.
Lin, M.A. and Papazian, D.M. Differences between ion binding to eag and HERG voltage sensors contribute to differential regulation of activation and deactivation gating. . Channels 2007; 1: 429-437.
Waters MF, Minassian NA, Stevanin G, Figueroa KP, Bannister JPA, Nolte D, Mock AF, Evidente VG, Fee D, Muller U, Durr A, Brice A, Papazian DM, and Pulst DM Mutations in the voltage-gated potassium channel KCNC3 cause degenerative and developmental CNS phenotypes. Nat. Genet 2006; 38: 447-451.
Bannister JPA, Chanda B, Bezanilla F, and Papazian DM Optical detection of rate-determining, ion-modulated conformational changes of the ether-a-go-go K+ channel voltage sensor. Roc. Natl. Acad. Sci. USA 2005; 102: 18718-18723.
Silverman, WR Bannister, JP Papazian, DM Binding site in eag voltage sensor accommodates a variety of ions and is accessible in closed channel. Biophysical journal. . 2004; 87(5): 3110-21.
Laine M, Lin MA, Bannister JPA, Silverman WR, Mock AF, Roux B, and Papazian DM Atomic proximity between S4 segment and pore domain in Shaker potassium channels. Neuron 2003; 39: 467-481.