James Trimmer, Ph.D.
1163 Life Sciences
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.
2015 Gong, B., Murray, K. D., and J. S. Trimmer. Developing High-Quality Mouse Monoclonal Antibodies for Neuroscience Research – Approaches, Perspectives and Opportunities. New Biotech. (in press). PMID: 26644354.
2015 Cobb, M. M., Austin, D. C., Sack, J. T., and J. S. Trimmer. (2015). Cell Cycle-Dependent Changes in Localization and Phosphorylation of the Plasma Membrane Kv2.1 K+ Channel Impact Endoplasmic Reticulum Membrane Contact Sites in COS-1 Cells. J. Biol. Chem. 290:29189-29201. PMID: 26442584.
2015 Bishop, H. I., Guan, D., Bocksteins, E., Parajuli, L., Murray, K. D., Cobb, M. M., Misonou, H., Zito, K., Foehring, R. C., and J. S. Trimmer. (2015). Distinct Cell- and Layer-Specific Expression Patterns and Independent Regulation of Kv2 Channel Subtypes in Cortical Pyramidal Neurons. J. Neurosci. 35:14922-14942. PMID: 26538660.
2015 Thiffault, I., Speca, D. J., Austin, D. C., Cobb, M. M., Eum, K. S., Safina, N. P., Grote, L., Farrow, E. G., Miller, N., Soden, S., Kingsmore, S. F., Trimmer, J. S., Saunders, C. J., and J. T. Sack. (2015) A Novel Epileptic Encephalopathy Mutation in KCNB1 Disrupts Kv2.1 Ion Selectivity, Expression, and Localization. J. Gen. Physiol. 146:399-410. PMID: 26503721.
2015 Cerda, O., Leiva-Salcedo, E., Park, K.-S., Cáceres, M., Romeroa, A., Varela, D., Trimmer, J. S., and A. Stutzinband. (2015). Casein Kinase-Mediated Phosphorylation of Serine 839 Is Necessary for Basolateral Localization of the Ca2+-Activated Non-Selective Cation Channel TRPM4. Pflugers Arch. 467: 1723-1732. PMID: 25231975.
2015 Jan, L. Y., Attali, B., Nerbonne, J., Sanguinetti, M. C., Trimmer, J. S., Chandy, K. G., Grissmer, S., Gutman, G. A., Lazdunski, M., Mckinnon, D., Pardo, L. A., Robertson, G. A., Rudy, B., Stühmer, W., and X. Wang. Voltage-Gated Potassium Channels. IUPHAR/BPS Guide to PHARMACOLOGY,
2015 Cáceres, M., Ortiz, L., Romero, A., Recabarren, T., Colombo, A., Leiva-Salcedo, E., Varela, D., Rivas, J., Silva, I., Campusano, C., Almarza, O., Simón, F., Toledo, H., Park, K.-S., Trimmer, J. S., and O. Cerda. (2015). TRPM4 is a Novel Component of the Adhesome Required for Focal Adhesion Disassembly, Migration and Contractility. PLoS ONE 10:e0130540. PMID: 26110647.
2015 Hirono, M., Ogawa, Y., Misono, K., Zollinger, D. R., Trimmer, J. S., Rasband, M. N., and H. Misonou. (2015). BK Channels Localize to the Paranodal Junction and Regulate Action Potentials in Myelinated Axons of Cerebellar Purkinje Cells. J. Neurosci. 35:7082-7094. PMID: 25948259.
2015 Trimmer, J. S., and H. Misonou. (2015). Ion Channel Phosphorylation. (Chapter 36, pages 531-544). InThe Handbook of Ion Channels. (J. Zheng and M. C. Trudeau, Editors). CRC Press, Boca Raton, FL.
2015 Hsiao, J. J., Ng, B. H., Smits, M. M., Wang, J., Jasavala, R. J., Martinez, H. D., Lee, J. A., Alston, J. J., Misonou, H., Trimmer, J. S., and M. E. Wright. (2015). Androgen Receptor and Chemokine Receptors 4 and 7 Form a Signaling Axis to Regulate CXCL12-Dependent Cellular Motility. BMC Cancer 15:204. PMID: 25884570.
2015 Trimmer, J. S. (2015). Subcellular Localization of K+ Channels in Mammalian Brain Neurons: Remarkable Precision in the Midst of Extraordinary Complexity. Neuron 85: 238-256. PMID: 25611506.
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: 190-194
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.
- 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
- NPB 107, Cell Signaling in Health and Disease
- National Institutes of Health