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Papazian Lab Homepage Home Contact People Positions Projects
Electrical excitability in the brain: voltage-gated ion channels, cell & circuit function, neural control of behavior, relationship between spike activity and neuronal viability. Electrical activity underlies most aspects of brain function. Our research focuses on the voltage-gated ion channels that confer electrical excitability on neurons and the consequences of changes in channel activity for neuronal firing, circuit function, behavior, and neuronal viability during development and aging. Work in our lab spans many levels of analysis, from the molecular to the behavioral. We are studying how voltage controls the activity of K+ channels, how changes in channel function or expression affect the firing patterns of neurons and the emergent properties of neuronal circuits, and how altering neuronal excitability affects behavior. We are also investigating the relationship between excitability and neuronal survival at different stages of life. We use a wide variety of experimental approaches to address these issues, including electrophysiology, imaging, biochemistry, molecular biology, genetics, and behavioral analysis. In the past few years, we have adopted the zebrafish, Danio rerio, as our main model system for integrative analysis. We also use Xenopus oocytes to investigate channel function and primary cultures of rodent neurons to explore the relationship between channel activity and neuronal function and viability. We are always looking for bright, hard-working individuals who want to work in a collaborative environment focusing on mechanistic, quantitative approaches to key questions in neuroscience. Home People Projects Publications Contact Positions Map & Directions Links
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Electrical activity underlies most aspects of brain function
Electrical activity underlies most aspects of brain function. Our research focuses on the voltage-gated ion channels that confer electrical excitability on neurons and the consequences of changes in channel activity for neuronal firing, circuit function, behavior, and neuronal viability during development and aging. Work in our lab spans many levels of analysis, from the molecular to the behavioral. We are studying how voltage controls the activity of K+ channels, how changes in channel function or expression affect the firing patterns of neurons and the emergent properties of neuronal circuits, and how altering neuronal excitability affects behavior. We are also investigating the relationship between excitability and neuronal survival at different stages of life. We use a wide variety of experimental approaches to address these issues, including electrophysiology, imaging, biochemistry, molecular biology, genetics, and behavioral analysis. In the past few years, we have adopted the zebrafish, Danio rerio, as our main model system for integrative analysis. We also use Xenopus oocytes to investigate channel function and primary cultures of rodent neurons to explore the relationship between channel activity and neuronal function and viability. We are always looking for bright, hard-working individuals who want to work in a collaborative environment focusing on mechanistic, quantitative approaches to key questions in neuroscience.
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People Current Lab Members Former Lab Members
Home Projects Publications Contact Positions Map & Directions Links Current Lab Members Jie Yi (Ray) Hsieh Fadi (Pete) Issa Meng-chin Lin Natali Minassian Allan Mock Liz Vuong Former Lab Members Chih-Yung Tang, National Taiwan University Seema Tiwari-Woodruff, UCLA Lucia Santacruz-Toloza, Duke University Christine Schulteis, Immusol Will Silverman, University of Miami Muriel Lainé, University of Chicago John Bannister, University of Tennessee Chris Mazzochi Jessica Richardson, UC Davis School of Law Myong-chul Koag Mike Myers, Cal State Long Beach Diane M Papazian PhD Professor Department of Physiology UCLA Raj Khanna, Indiana University Naomi Nagaya, University of Michigan Yu Huang, Chinese University of Hong Kong Scott John, UCLA Max Shao, UCLA Sang-Ah Seoh Miriam Pillos Lab Photos
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Diane M Papazian PhD Professor Department of Physiology UCLA
Education: B.S. (Chemistry), with high distinction University of Michigan Ann Arbor, Michigan Ph.D. (Biological Chemistry) Harvard University Cambridge, Massachusetts Professional Positions: Postdoctoral Fellow Laboratory of Lily and Yuh Nung Jan University of California, San Francisco Assistant Professor, Department of Physiology UCLA School of Medicine Associate Professor, Department of Physiology Executive Vice Chair, Department of Physiology UCLA David Geffen School of Medicine 2000-now Professor, Department of Physiology Honors: Fellow of the Biophysical Society, 2009 H. W. Magoun Distinguished Lecturer, UCLA Brain Research Institute, 2008 Contributing Member, Faculty of 1000, Councilor, Biophysical Society, Fellow, American Association for the Advancement of Science, 1999 Grass Foundation Traveling Scientist, Society for Neuroscience, 1997 Pew Scholar in the Biomedical Sciences, Klingenstein Fellow in the Neurosciences, Home Back to People
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Jie Yi (Ray) Hsieh Home Back to People
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Fadi (Pete) Issa PhD Home Back to People
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Meng-chin A Lin PhD Home Back to People
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Natali A Minassian Home Back to People
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Allan Mock Home Back to People
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Papazian Lab Photos Home Back to People
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Projects Gating of voltage-dependent K+ channels (more . . .) Home
People Publications Contact Positions Map & Directions Links Projects Neuronal Excitability and Spinocerebellar Ataxia Type 13 (more . . .) Spinocerebellar Ataxia Type 13 is an autosomal dominant genetic disease in humans caused by mutations in KCNC3, which encodes Kv3.3, a voltage-gated K+ channel. The two original SCA13 mutations are associated with distinct clinical manifestations. A mutation in the voltage sensor domain leads to progressive adult onset ataxia accompanied by degeneration of cerebellar neurons. This mutant subunit has a strong dominant negative effect on Kv3 expression. In contrast, a mutation in the pore domain causes a form of SCA13 that emerges in infancy, characterized by a severely shrunken and malformed cerebellum and non-progressive motor deficits. This mutation affects gating, shifting the voltage dependence of activation in the negative direction and dramatically slowing channel closing. We are testing the hypothesis that changes in Kv3.3 channel function alter the excitability of cerebellar neurons, with detrimental consequences for motor behavior and neuronal survival during brain development or aging. We are working to determine how changes in excitability decrease the viability of neurons and why different mutations affect neuronal survival at different stages of life. Zebrafish Model of Human Ataxia (more . . .) We are expressing SCA13 mutant subunits in zebrafish to determine the consequences for neuronal function, development, viability, and locomotor behavior. Currently, we are focusing on the spinal cord. Endogenous Kv3.3 is expressed in primary motor neurons, which control the fastest and largest amplitude movements in zebrafish, including the startle (escape) response. Expression of a dominant negative SCA13 subunit dramatically affects the escape response, reducing the precision and amplitude of the C start and impairing the execution of subsequent steps in the motor program. These features strongly resemble human ataxia. Gating of voltage-dependent K+ channels (more . . .) We are investigating the mechanism of voltage-dependent activation in K+ channels. K+ channels are tetramers with a central K+-selective pore and 4 voltage sensor domains, one per subunit. Upon membrane depolarization, the voltage sensor domains undergo conformational changes that result in pore opening. Our current goals are to identify experimental constraints that make it possible to model the structure of the closed channel and to determine the pathway taken by the S4 segment, the main moving element in the voltage sensor, during activation.
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Selected Recent Publications
Home People Projects Contact Positions Map & Directions Links Full Publication List (PubMed)
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Home People Projects Publications Positions Map & Directions Links Contact Information U.S. Mailing Address: Department of Physiology David Geffen School of Medicine at UCLA 650 Charles Young Drive South Box , Room CHS Los Angeles, CA Diane M Papazian PhD Phone: (310) Lab: (310) Fax: (310) Shipping Address: Medical Receiving UCLA Physiology 650 Charles Young Drive South Box , Room CHS Los Angeles, CA Campus Address: Department of Physiology CHS Mail code
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Positions Graduate Students
Home People Projects Publications Contact Links Map & Directions Graduate Students Prospective graduate students have the option of applying to UCLA Access or directly to the Indepartmental PhD Programs in Neuroscience or in Molecular, Cellular and Integrative Physiology. Postdoctoral Fellows Recent PhD recipients with training relevant to our research are invited to apply. Please send your CV and the names of three references to Diane Papazian. At this time, only postdoc candidates who have or can raise their own salary support are being considered. Staff Research Positions We occasionally have open positions for Staff Research Associates. These jobs are posted at: (URL) Research Experiences for Undergraduates Motivated undergraduates who are interested in specific projects in the lab should contact Diane Papazian. Only undergraduates who will commit to spending a minimum of 15 hours per week at the bench will be considered.
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Map & Directions Campus map Westwood
Home People Projects Publications Contact Positions Links Map & Directions From the 405, exit on Wilshire Blvd heading east. Turn left on Westwood Blvd and follow it onto campus. Turn right at Charles Young Dr. South. You can enter The Center for Health Sciences through the School of Public Health on the south side of the block ( ). We are on the 5th floor, CHS. Campus map Westwood
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Links Molecular, Cellular and Integrative Physiology PhD Program
Home People Projects Publications Contact Positions Map & Directions Links Molecular, Cellular and Integrative Physiology PhD Program Neuroscience PhD Program UCLA Access Department of Physiology Brain Research Institute Molecular Biology Institute Science Links News & Politics Los Angeles California
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