Kelsey Martin, M.D., Ph.D.
Office Phone Number:
UCLA Biol Chem
615 Charles E Young
BOX 951737, 390-B BSRB
Los Angeles, CA 90095
615 Charles E. Young Dr. S.
Los Angeles, CA 90095
Psychiatry and Biobehavioral Sciences
UCLA-Caltech Medical Scientist Training Program
ACCESS Program: Dept. of Biological Chemistry
Access Cell and Developmental Biology Home Area
Access Neuroscience Home Area
Brain Research Institute
Center for Neurobehavioral Genetics
A Short Biography:
Dr. Kelsey Martin is a professor and chair of biological chemistry. Her research focuses on the cell biology of transcription-dependent forms of synaptic plasticity, particularly those underlying learning and memory. Her lab studies both directions of signaling between synapse and nucleus, focusing on 1) the role of the active nuclear import pathway in transport of signals from synapse to nucleus and 2) mRNA localization and regulated translation as a mechanism for spatially restricting the products of gene expression to specific synapses within a single neuron. These studies use a combination of cell biology, molecular biology and electrophysiology in cultured sensory-motor neurons from the marine invertebrate Aplysia californica, and cultured neurons from mouse hippocampus, and involve investigation of the function of specific molecules in neurons.
Dr. Martin will use the newly available Aplysia reference sequence together with RNA interference to conduct genetic screens in Aplysia. As the group identifies molecules that play roles in plasticity in reduced preparations, it will study the function of these molecules in vivo using genetically modified animals, e.g. BAC transgenic mice generated by William Yang. The availability of high throughput genomic and proteomic methodologies have allowed her group to identify, in an unbiased manner, populations of mRNAs that are present in dendrites (by microarray analysis, in collaboration with Dan Geschwind) and to identify proteins that interact with importin nuclear transporters (by mass spectrometric analysis). Her lab will collaborate with CNG members who identify genes underlying neuropsychiatric disorders and want to use cell and molecular biology to study the function of those genes.
Awards and Honors:
Columbia University, New York
Chair, Meeting on RNA Localization
Gordon Research Conference
Chair, Meeting on Cell Biology of the Neuron
Chair, Meeting on RNA Localization
Independent Investigator Award
Eleanor Leslie Term Chair in Innovative Brain Research
Foundation Scholar Award
Daniel X. Freeman Award
American Society of Neurochemistry
Jordi Folch-Pi Award
Fellowship in the Neurosciences
W.M. Keck Foundation
Distinguished Young Scholar Award
Burroughs Wellcome Fund
Career Award in the BiomedicalSciences
Young Investigator Award
Cell Biology of Learning-related Synaptic Plasticity
Synaptic plasticity, the modification of connections in the brain by experience, is the best correlate of learning and memory in invertebrate and vertebrate animals. Long-lasting forms of synaptic plasticity have been shown to require gene expression. This means that signals must be transported from the synapse, where they are generated, to the nucleus, where they are converted into changes in gene expression. The products of gene expression must then be transported from the cell soma to the synapse to produce enduring changes in synaptic strength. My lab is interested in both aspects of communication between the synapse and the nucleus during synaptic plasticity in neurons. We study these questions in cultured Aplysia sensory-motor neurons and in cultured rodent hippocampal neurons using cell biological, molecular biological and electrophysiological techniques.
Tranport of molecules from the synapse to the nucleus of neurons is particularly challenging because synapses are often very far from the cell body. We are focusing on the role of the active nuclear import pathway in mediating this transport. We find that the importin nuclear transport factors are present in distal synapses, and that distinct stimuli trigger the nuclear translocation of distinct importin alpha isoforms. We are now interested in understanding how synaptic stimulation triggers their nuclear import, in understanding the pathways whereby the importin-cargo complex travels from synapse to nucleus, and in identifying some of the cargoes themselves.
Since each neuron has a single nucleus but can form thousands of synaptic connections, the requirement for transcription during synaptic plasticity raises the question of how the products of gene expression can be targeted to alter synaptic strength at select synapses made by a given neuron. We have found that one important mechanism whereby long-lasting, transcription-dependent plasticity can occur in a synapse-specific manner involves the translation of synaptically localized mRNAs. Another mechanism involves local, regulated degradation of proteins via the ubiquitin proteasome pathway. We are using a variety of molecular, cell biological and pharmacological approaches to identify dendritically localized mRNAs, to study the regulated translation of these mRNAs, and to study the role of local protein degradation during synaptic plasticity.
Kelsey Martin, Professor in the Department of Biological Chemistry, Eleanor Leslie Term Chair in Innovative Brain Research, and Co-Director of the UCLA-Caltech Medical Scientist Training Program (MSTP), is interested in the molecular and cell biology of learning and memory. Her lab studies long-term synaptic plasticity, the process whereby neurons change the strength and number of their synaptic connections with experience. Long-term forms of synaptic plasticity, like long-term memory, require new gene expression. The Martin lab focuses on two questions that emerge from this requirement: 1) how are signals received at distal synapses relayed to the nucleus to turn on transcription? and 2) how can gene expression be spatially restricted within the neuron to allow synapse-specific forms of transcription-dependent plasticity? They study these questions using two model systems of learning-related synaptic plasticity: Aplysia sensory-motor synapses and rodent hippocampal synapses, using a combination of electrophysiology, biochemistry, cell and molecular biology.
In 2004, the Martin lab discovered a role for importin-mediated active nuclear transport in carrying signals from the synapse to the nucleus during long-term synaptic plasticity. Current efforts are focused on identifying the synaptically-localized protein cargoes of importins and on understanding the cell biological pathway underlying this long-distance retrograde transport. In 1997, Kelsey Martin discovered that synapse-specific forms of long-term plasticity require translation of localized mRNAs at the synapse. The Martin lab has since identified a large population of mRNAs that are present in neurites of Aplysia sensory neurons and and dendrites of rodent hippocampal neurons. Using a combination of in situ hybridization, live cell imaging of RNA and translational reporters, siRNA-mediated gene silencing and electrophysiological recording, they are investigating the mechanisms underlying mRNA localization and regulated translation in neurons as well as the function of this form of regulated gene expression during synapse formation and synaptic plasticity. The goal of these studies is to understand how the brain forms and stores memories, and to provide insights into the pathophysiology of disorders in which learning and memory are impaired.
Dzudzor Bartholomew, Huynh Lucia, Thai Minh, Bliss Joanne M, Nagaoka Yoshiko, Wang Ying, Ch'ng Toh Hean, Jiang Meisheng, Martin Kelsey C, Colicelli John
Regulated expression of the Ras effector Rin1 in forebrain neurons
Molecular and cellular neurosciences,
Lyles, V., Zhao, Y. and Martin, K.C.
Synapse formation and mRNA localization in Aplysia sensory-motor neurons,
Ormond, J Hislop, J Zhao, Y Webb, N Vaillaincourt, F Dyer, JR Ferraro, G Barker, P Martin, KC Sossin, WS
ApTrkl, a Trk-like receptor, mediates serotonin- dependent ERK activation and long-term facilitation in Aplysia sensory neurons
Ormond Jake, Hislop Jonathan, Zhao Yali, Webb Neil, Vaillaincourt Francois, Dyer John R, Ferraro Gino, Barker Phil, Martin Kelsey C, Sossin Wayne S
ApTrkl, a Trk-like receptor, mediates serotonin- dependent ERK
activation and long-term facilitation in Aplysia sensory neurons
Martin, K.C. and Sun, Y.I
To Learn Better, Keep Your HAT On,
Moccia, R Chen, D Lyles, V Kapuya, E E, Y Kalachikov, S Spahn, CM Frank, J Kandel, ER Barad, M Martin, KC
An unbiased cDNA library prepared from isolated Aplysia sensory neuron processes is enriched for cytoskeletal and translational mRNAs
The Journal of Neuroscience. ,
Moccia Robert, Chen Dillon, Lyles Vlasta, Kapuya Estreya, E Yaping, Kalachikov Sergey, Spahn Christian M T, Frank Joachim, Kandel Eric R, Barad Mark, Martin Kelsey C
An unbiased cDNA library prepared from isolated Aplysia sensory neuron
processes is enriched for cytoskeletal and translational mRNAs
The Journal of neuroscience : the official journal of the Society for Neuroscience,
Martin, K.C., and Kosik, K.S
Synaptic Tagging - Who's it?,
Nature Neurosci. Rev,
Patterson, S.L., Pittenger, C., Morozov, A., Martin, K.C., Scanlin, H., Drake, C., and Kandel, E.R
Some forms of cAMP-mediated long-lasting potentiation are associated with release of BDNF and nuclear translocation of phospho-MAP kinase,
Martin, K.C., Bartsch, D., Bailey, C.H. and Kandel,E.R.
Molecular mechanisms underlying learning-related long-lasting synaptic plasticity,
The New Cognitive Neurosciences,
2000; 2nd edition:
Casadio, A.*, Martin, K.C.*, et al.
A novel, transient form of CREB-mediated long-term facilitation that is neuron-wide and can be stabilized at specific synapses by local rapamycin-sensitive protein synthesis,
Winder, D.G., Martin, K.C., Muzzio, I., Rohrer, D., Chruscinski, A., Kobilka, B. and Kandel, E.R.
ERK plays a novel role in the induction of LTP by theta frequency stimulation and its regulation by beta-adrenergic receptors in CA1 pyramidal cells,
Martin, KC Casadio, A Zhu, H Yaping, E Rose, JC Chen, M Bailey, CH Kandel, ER
Synapse-specific, long-term facilitation of aplysia sensory to motor synapses: a function for local protein synthesis in memory storage