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Department of Physiology and Membrane Biology

Department of Physiology and Membrane Biology

James Trimmer, Ph.D.

James Trimmer, Ph.D.

Professor
1163 Life Sciences
Davis Campus
(530) 754-6075
e-mail

Recent/Current Research Funding

National Institutes of Health

Graduate Group Affiliations

Biochemistry, Molecular Cellular and Developmental Biology

Neuroscience

Research Interests

As neuroscience enters the post-genomic era, a major goal is the translation of genomic sequence information into a molecular understanding of the mechanisms of neuronal information processing and transfer. My laboratory’s research focuses on protein function, biochemical pathways and networks of protein-protein interactions regulating intra- and inter-cellular signaling in mammalian neurons. In particular, we are interested in dynamic regulation of voltage-sensitive ion channel abundance, localization and function through reversible protein phosphorylation. These proteins determine the intrinsic electrical properties of neurons and how these cells respond to external stimuli, integrate the encoded information and generate an appropriate response. Modern proteomic techniques have allowed for insights into protein networks, and post-translational modifications, that provide for both the generation and maintenance of complex cellular functions, but also their dynamic regulation that underlies functional plasticity. Our studies are aimed at a molecular understanding of how neuronal ion channels generate and maintain the fidelity of neuronal signaling, and how these processes can be dynamically regulated to generate neuronal plasticity. Such information is necessary for an increased understanding of not only the normal functional plasticity of neurons, but also in understanding of disease states where neuronal function is altered and effects of acute external insults such as ischemia and drugs of abuse, and represent a key step towards the development of therapeutics that can address these and other psychiatric and neurological disorders. Moreover, these studies are representative of approaches that would prove advantageous to studies on other neuronal signaling proteins. To better translate findings from genome-based studies, we have also established the UC Davis/NIH NeuroMab facility, to use information on proteins encoded in the human and other genomes to generate monoclonal antibodies for use in the research community.

 

Representative Publications

2014  Cerda, O., Leiva-Salcedo, E., Park, K.-S., Cáceres, M., Romeroa, A., Varela, D., Trimmer, J. S., and A. Stutzinband. Casein Kinase-Mediated Phosphorylation of Serine 839 Is Necessary for Basolateral Localization of the Ca2+-Activated Non-Selective Cation Channel TRPM4. Pflugers Arch (in press).

2014  The Handbook of Ion Channels. (J. Zheng and M. C. Trudeau, Editors). Taylor and Francis Books, Inc., Oxon, UK. (in press).

2014  Mandikian, D., Bocksteins, E., Parajuli, L., Bishop, H. I., Cerda, O., Shigemoto, R., and J. S. Trimmer. Cell Type Specific Spatial and Functional Coupling Between Mammalian Brain Kv2.1 K+ Channels and Ryanodine Receptors. J. Comp. Neurol. 522: 3555-3574.

2014  King, A. N., Manning, C. F., and J. S. Trimmer. A Unique Ion Channel Clustering Domain on the Axon Initial Segment of Mammalian Neurons. J. Comp. Neurol.  522: 2594-2608.

2014  Baek, J.-H., Rubinstein, M., Scheuer, T., and J. S. Trimmer. Reciprocal Changes in Phosphorylation and Methylation of Mammalian Brain Sodium Channels in Response to Seizures. J. Biol. Chem. 289: 15363-15373.

2014  Trimmer, J. S. Ion Channels and Pain: Important Steps Towards Validating a New Therapeutic Target for Neuropathic Pain. Exp. Neurol. 254:

2014  Speca, D. J., Ogata, G., Mandikian, D., Bishop, H. I., Wiler, S. W., Eum, K., Wenzel, H. J., Doisy, E. T., Matt, L., Campi, K. L., Golub, M. S., Nerbonne, J. M., Hell, J. W., Trainor, B., Sack, J. T., Schwartzkroin P. A., and J. S. Trimmer. Deletion of the Kv2.1 Delayed Rectifier Potassium Channel Leads to Neuronal and Behavioral Hyperexcitability. Genes, Brain and Behavior 13: 394-408.

2013  Sack, J. T., Stephanopoulos, N., Austin, D. C., Francis, M. B., and J. S. Trimmer. Antibody guided photoablation of voltage-gated potassium currents. J. Gen. Physiol. 142:315-324. 

2012  Vacher, H., and J. S. Trimmer. Trafficking Mechanisms Underlying Neuronal Voltage-gated Ion Channel Localization at the Axon Initial Segment. Epilepsia 53 (suppl. 9): 21-31.

2012  Manning, C. F., Bundros, A. M., and J. S. Trimmer. Benefits and Pitfalls of Secondary Antibodies: Why Choosing The Right Secondary is of Primary Importance. PLoS ONE 7: e38313.

2012  Menegola, M., Clark, E., and J. S. Trimmer. The Importance of Immunohistochemical Analyses in Evaluating the Phenotype of Kv Channel Knockout Mice. Epilepsia 53 (suppl. 1): 142-149.

2011  Vacher, H., and J. S. Trimmer. Diverse Roles for Auxiliary Subunits in Phosphorylation-Dependent Regulation of Mammalian Brain Voltage-Gated Potassium Channels. Pflugers Arch. 462:631-643.

2011  Cerda, O., and J. S. Trimmer. Activity-Dependent Phosphorylation of Neuronal Kv2.1 Potassium Channels by CDK5. J. Biol. Chem. 286:28738-28748.

2011  Baek, J.-H., Cerda, O., and J. S. Trimmer. Mass Spectrometry-Based Phosphoproteomics Reveals Multisite Phosphorylation on Mammalian Brain Voltage-Gated Sodium and Potassium Channels. Semin. Cell Dev. Biol. 22:153-159.

2011  Trimmer, J. S. How Native Cells Regulate Their Ion Channels. Semin. Cell Dev. Biol. 22:131.

2011  Mandikian, D., Cerda, O., Sack, J. T., and J. S. Trimmer. A SUMO-Phospho Tag Team for Wrestling with Potassium Channel Gating. J. Gen. Physiol. 137:435-439.

2011  Vacher, H., Yang, J.-W., Cerda, O., Autillo-Touati, A., Dargent, B., and J. S. Trimmer. CDK-Mediated Phosphorylation of the Kvβ2 Auxiliary Subunit Regulates Kv1 Channel Axonal Targeting. J. Cell Biol. 192: 813-824.

2011  Cerda, O., Baek, J.-H., and J. S. Trimmer. Mining Recent Brain Proteomic Databases for Ion Channel Phosphosite Nuggets. J. Gen. Physiol. 137: 3-16.

 

Recent/Current Teaching

NPB 107, Cell Signaling in Health and Disease

 

Teaching and Research Awards

  • Established Investigatorship, American Heart Association
  • National Institute of Neurological Disorders and Stroke, National Institutes of Health, Jacob Javits Neuroscience Investigator (MERIT) Award
  • UC Davis Graduate Student Association Award for Excellence in Service to Graduate Students