Office Phone Number:
615 Charles E Young
BOX 951737, 390-B BSRB
Los Angeles, CA 90095
615 Charles E. Young Dr. S.
Los Angeles, CA 90095
|Dean, David Geffen School of Medicine at UCLA|
|Professor, Biological Chemistry, Psychiatry and Biobehavioral Sciences|
Kelsey C. Martin, M.D., Ph.D., is Executive Vice Dean and Associate Vice Chancellor of the David Geffen School of Medicine at UCLA. She received her undergraduate degree in English and American Language and Literature at Harvard University. After serving as a Peace Corps volunteer in the Democratic Republic of Congo, she entered the MD-PhD program at Yale University where she studied influenza virus-host cell interactions in the laboratory of Dr. Ari Helenius, receiving her PhD degree in Molecular Biophysics and Biochemistry and her MD degree in 1992. She did her postdoctoral training in neurobiology with Dr. Eric Kandel at Columbia University, and joined the UCLA faculty in 1999. The Martin lab integrates cell biological, molecular and electrophysiological approaches to understand how experience changes brain connectivity to store memories. Their studies focus primarily on the spatial and temporal regulation of gene expression during long-lasting memory formation. Dr. Martin is on the editorial board of Cell and the scientific advisory boards of the Burroughs Wellcome Career Awards in Medicine and the McKnight Scholar Awards. She also serves as Chair of Basic Science Chairs and Chair of the Neuroscience Research Theme within the UCLA David Geffen School of Medicine.
How Does the Brain Store Memories?
Experience changes the strength and number of synaptic connections between neurons in the brain. This process, known as synaptic plasticity, provides a cellular mechanism for memory storage. Research in the Martin lab is aimed at understanding the cell and molecular biology of synaptic plasticity in mouse and Aplysia model systems. The results of their research shed light not only on healthy brain function, but also on the causes of many brain disorders in which neuronal plasticity and memory formation are altered, including mental retardation, autism spectrum disorders, drug addiction, anxiety disorders, and Alzheimers disease.
Long-term forms of plasticity, such as those underlying long-term memory, require new RNA and protein synthesis. This means that signals are transported from the synapse, where they are generated, to the nucleus, where they alter transcription. The transport of molecules from the synapse to the nucleus of neurons is particularly challenging because synapses are often very far from the cell body. The Martin lab has discovered a role for the active transport of signals from stimulated synapses to the nucleus during long-term neuronal plasticity. Current research is aimed at identifying synaptically localized signaling molecules that undergo stimulus-induced active nuclear import during plasticity, and at understanding the cell biological pathways that mediate long-distance retrograde transport from synapse to nucleus. In studies focused on the transcriptional regulator CRTC1, the Martin lab is exploring how specific patterns of neuronal stimulation trigger specific programs of transcription, and how neuromodulators such as dopamine and norepinephrine regulate the programs of gene expression that give rise to long-lasting plasticity. This work provides molecular insights into the role of emotion and attention in memory formation.
Research in the Martin lab also addresses the mechanisms by which transcription-dependent plasticity can occur at subsets of the thousands of synapses that are made by an individual neuron. Dr. Martin and her colleagues have shown that one important mechanism for restricting gene expression to stimulated synapses involves the regulated translation of synaptically localized mRNAs. Studies in her lab are aimed at identifying the populations of mRNAs that localize to synapses, the molecular mechanisms underlying the localization and translation of these mRNAs, as well as the function of local translation in long-term memory. Recent transcriptome and translatome profiling experiments suggest that the regulation of gene expression in neurons is highly decentralized and compartmentalized during plasticity, with transcriptional regulation placing the entire neuronal arbor in a state of readiness to respond to local cues via local translation to change the structure and function of subsets of synapses.
Kim Sangmok, Martin Kelsey C Neuron-wide RNA transport combines with netrin-mediated local translation to spatially regulate the synaptic proteome. eLife. 2015; 4: .
Ho Victoria M, Dallalzadeh Liane O, Karathanasis Nestoras, Keles Mehmet F, Vangala Sitaram, Grogan Tristan, Poirazi Panayiota, Martin Kelsey C GluA2 mRNA distribution and regulation by miR-124 in hippocampal neurons. Molecular and cellular neurosciences. 2014; 61: 1-12.
Ch'ng Toh Hean, Uzgil Besim, Lin Peter, Avliyakulov Nuraly K, O'Dell Thomas J, Martin Kelsey C Activity-Dependent Transport of the Transcriptional Coactivator CRTC1 from Synapse to Nucleus. Cell. 2012; 150(1): 207-21.
Meer Elliott J, Wang Dan Ohtan, Kim Sangmok, Barr Ian, Guo Feng, Martin Kelsey C Identification of a cis-acting element that localizes mRNA to synapses. Proceedings of the National Academy of Sciences of the United States of America. 2012; 109(12): 4639-44.
Ho Victoria M, Lee Ji-Ann, Martin Kelsey C The cell biology of synaptic plasticity. Science (New York, N.Y.). 2011; 334(6056): 623-8.
Ch'ng Toh Hean, Martin Kelsey C Synapse-to-nucleus signaling. Current opinion in neurobiology. 2011; 21(2): 345-52.
Martin Kelsey C Anchoring local translation in neurons. Cell. 2010; 141(4): 566-8.
Wang Dan Ohtan, Martin Kelsey C, Zukin R Suzanne Spatially restricting gene expression by local translation at synapses. Trends in neurosciences. 2010; 33(4): 173-82.
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. 2010; 43(1): 108-16.
Jeffrey Rachel A, Ch'ng Toh Hean, O'Dell Thomas J, Martin Kelsey C Activity-dependent anchoring of importin alpha at the synapse involves regulated binding to the cytoplasmic tail of the NR1-1a subunit of the NMDA receptor. The Journal of Neuroscience. 2009; 29(50): 15613-20.
Zhao Yali, Wang Dan O, Martin Kelsey C Preparation of Aplysia sensory-motor neuronal cell cultures. Journal of Visualized Experiments. 2009; 324(28): .
Wang Dan Ohtan, Kim Sang Mok, Zhao Yali, Hwang Hongik, Miura Satoru K, Sossin Wayne S, Martin Kelsey C Synapse- and stimulus-specific local translation during long-term neuronal plasticity. Science (New York, N.Y.). 2009; 324(5934): 1536-40.
Martin Kelsey C, Ephrussi Anne mRNA localization: gene expression in the spatial dimension. Cell. 2009; 136(4): 719-30.
Shobe Justin L, Zhao Yali, Stough Shara, Ye Xiaojing, Hsuan Vickie, Martin Kelsey C, Carew Thomas J Temporal phases of activity-dependent plasticity and memory are mediated by compartmentalized routing of MAPK signaling in aplysia sensory neurons. Neuron. 2009; 61(1): 113-25.
Lai Kwok-On, Zhao Yali, Ch'ng Toh Hean, Martin Kelsey C Importin-mediated retrograde transport of CREB2 from distal processes to the nucleus in neurons. Proceedings of the National Academy of Sciences of the United States of America. 2008; 105(44): 17175-80.
Delgado Jary Y, Coba Marcelo, Anderson Christopher N G, Thompson Kimberly R, Gray Erin E, Heusner Carrie L, Martin Kelsey C, Grant Seth G N, O'Dell Thomas J NMDA receptor activation dephosphorylates AMPA receptor glutamate receptor 1 subunits at threonine 840. The Journal of Neuroscience. 2007; 27(48): 13210-21.
Poon Michael M, Choi Sang-Hyun, Jamieson Christina A M, Geschwind Daniel H, Martin Kelsey C Identification of process-localized mRNAs from cultured rodent hippocampal neurons. The Journal of Neuroscience. 2006; 26(51): 13390-9.
Zhao Yali, Leal Karina, Abi-Farah Carole, Martin Kelsey C, Sossin Wayne S, Klein Marc Isoform specificity of PKC translocation in living Aplysia sensory neurons and a role for Ca2+-dependent PKC APL I in the induction of intermediate-term facilitation. The Journal of Neuroscience. 2006; 26(34): 8847-56.
Martin Kelsey C, Zukin R Suzanne RNA trafficking and local protein synthesis in dendrites: an overview. The Journal of Neuroscience. 2006; 26(27): 7131-4.
Lyles, V., Zhao, Y. and Martin, K.C. Synapse formation and mRNA localization in Aplysia sensory-motor neurons. Neuron 2006; 49: 349-356.
Otis Klara Olofsdotter, Thompson Kimberly R, Martin Kelsey C Importin-mediated nuclear transport in neurons. Current Opinion in Neurobiology. 2006; 16(3): 329-35.
Lyles Vlasta, Zhao Yali, Martin Kelsey C Synapse formation and mRNA localization in cultured Aplysia neurons. Neuron. 2006; 49(3): 349-56.
Thompson, KR Otis, KO Chen, DY Zhao, Y O'Dell, TJ Martin, KC Synapse to nucleus signaling during long-term synaptic plasticity; a role for the classical active nuclear import pathway. Neuron. . 2004; 44(6): 997-1009.
Thompson Kimberly R, Otis Klara Olofsdotter, Chen Dillon Y, Zhao Yali, O'Dell Thomas J, Martin Kelsey C Synapse to nucleus signaling during long-term synaptic plasticity; a role for the classical active nuclear import pathway. Neuron. 2004; 44(6): 997-1009.
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. Neuron. . 2004; 44(4): 715-28.
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. Neuron. 2004; 44(4): 715-28.
Martin, K.C. and Sun, Y.I To Learn Better, Keep Your HAT On. Neuron 2004; 42: 879-881.
Martin, KC Local protein synthesis during axon guidance and synaptic plasticity. Current Opinion in Neurobiology. . 2004; 14(3): 305-10.
Martin Kelsey C Local protein synthesis during axon guidance and synaptic plasticity. Current opinion in neurobiology. 2004; 14(3): 305-10.
Martin Kelsey C, Sun Yi E To learn better, keep the HAT on. Neuron. 2004; 42(6): 879-81.
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. . 2003; 23(28): 9409-17.
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. 2003; 23(28): 9409-17.
Zhao, Y Hegde, AN Martin, KC The ubiquitin proteasome system functions as an inhibitory constraint on synaptic strengthening. Current Biology. 2003; 13(11): 887-98.
Zhao Yali, Hegde Ashok N, Martin Kelsey C The ubiquitin proteasome system functions as an inhibitory constraint on synaptic strengthening. Current biology : CB. 2003; 13(11): 887-98.
Martin Kelsey C Synaptic tagging during synapse-specific long-term facilitation of Aplysia sensory-motor neurons. Neurobiology of learning and memory. 2002; 78(3): 489-97.
Martin, KC Synaptic tagging during synapse-specific long-term facilitation of Aplysia sensory-motor neurons. Neurobiology of Learning and Memory. . 2002; 78(3): 489-97.
Martin Kelsey C, Kosik Kenneth S Synaptic tagging -- who's it?. Nature reviews. Neuroscience. 2002; 3(10): 813-20.
Martin, K.C., and Kosik, K.S Synaptic Tagging - Who's it?. Nature Neurosci. Rev 2002; 10: 813-820.
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. Neuron 2001; 32: 123-140.
Martin, KC Barad, M Kandel, ER Local protein synthesis and its role in synapse-specific plasticity. Current Opinion in Neurobiology. . 2000; 10(5): 587-92.
Huang, YY Martin, KC Kandel, ER Both protein kinase A and mitogen-activated protein kinase are required in the amygdala for the macromolecular synthesis-dependent late phase of long-term potentiation. The Journal of Neuroscience. . 2000; 20(17): 6317-25.
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: 121-137.
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. Cell 1999; 99: 221-237.
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. Neuron 1999; 24: 715-726.
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. Cell. . 1997; 91(7): 927-38.
Martin, KC Michael, D Rose, JC Barad, M Casadio, A Zhu, H Kandel, ER MAP kinase translocates into the nucleus of the presynaptic cell and is required for long-term facilitation in Aplysia. Neuron. . 1997; 18(6): 899-912.
Martin, KC Kandel, ER Cell adhesion molecules, CREB, and the formation of new synaptic connections. Neuron. . 1996; 17(4): 567-70.
Martin, KC Hu, Y Armitage, BA Siegelbaum, SA Kandel, ER Kaang, BK Evidence for synaptotagmin as an inhibitory clamp on synaptic vesicle release in Aplysia neurons. Proceedings of the National Academy of Sciences of the United States of America. . 1995; 92(24): 11307-11.
Skehel, PA Martin, KC Kandel, ER Bartsch, D A VAMP-binding protein from Aplysia required for neurotransmitter release. Science. . 1995; 269(5230): 1580-3.
Martin, K Helenius, A Nuclear transport of influenza virus ribonucleoproteins: the viral matrix protein (M1) promotes export and inhibits import. Cell. . 1991; 67(1): 117-30.
Martin, K Helenius, A Transport of incoming influenza virus nucleocapsids into the nucleus. Journal of Virology. . 1991; 65(1): 232-44.