Dr. Hey-Kyoung Lee is an professor of neuroscience at the Johns Hopkins University School of Medicine. Her research focuses on the cellular and molecular changes that happen at synapses to allow memory storage. The goals of her research include elucidating the mechanisms underlying cross-modal synaptic plasticity and exposing the events that occur in diseased brains.
Dr. Lee received her undergraduate degree in biology from Yonsei University in Seoul, Korea. She earned her PhD in neuroscience from Brown University in Providence, Rhode Island, and completed postdoctoral training in neuroscience at the Johns Hopkins University School of Medicine. Dr. Lee joined the Johns Hopkins faculty in 2011.
Prior to joining Johns Hopkins, Dr. Lee was an associate professor at the University of Maryland.
She was awarded The Sloan Research Fellowship in 2004 and was nominated as one of the "Yonsei 100 Women Leaders" in 2006. In 2009, Dr. Lee was awarded the Junior Faculty Award from the College of Chemical and Life Sciences at the University of Maryland.
Cellular/Molecular Mechanisms of Synaptic Plasticity Underlying Memory Formation
Our daily experience can trigger lasting memories, which are stored in our brains. Memories are stored ultimately by changing the way neurons convey information. More precisely, they are stored as changes in the function of synapses: the structures by which neurons contact and transmit signals to each other. My laboratory is interested in exploring the cellular and molecular changes that happen at the synapses to allow memory storage.
Combining various techniques, such as electrophysiological recording, biochemical/molecular analysis, and imaging, we are aiming to understand the cellular and molecular changes that happen during synaptic plasticity. It is well established that neural activity can trigger synaptic changes, such as long-term potentiation (LTP) and long-term depression (LTD), which are cellular models of learning and memory. However, in addition to LTP and LTD, more global mode of plasticity needs to be in place to provide stability to neural networks. Currently, we are examining molecular and cellular mechanisms of global homeostatic synaptic plasticity using sensory cortices as model systems. We found that loss of vision elicits global changes in excitatory synaptic transmission in primary visual cortex, which is primarily due to regulation of postsynaptic AMPA type glutamate receptors. Interestingly, vision loss triggers opposite changes in other primary sensory cortices, which we postulate underlies sensory compensation in blind. Elucidating the mechanisms underlying such cross-modal synaptic plasticity is one of the main research foci of the lab.
In addition to understanding the basic mechanisms of how experience alters the brain, we are also interested in elucidating the events that occur in diseased brains. Alzheimer's disease is a devastating memory disorder that affects the social well-being of affected individuals. In collaboration with Dr. Philip Wong at Johns Hopkins School of Medicine, we are analyzing various mouse models of Alzheimer's disease, especially focusing on the possible alterations in synaptic plasticity mechanisms.
Wang H., L. Song, A. Lee, F. Laird, P. C. Wong, and H.-K. Lee(2010) Mossy fiber long-term potentiation deficits in BACE1 knock-outs can be rescued by activation of alpha7 nicotinic acetylcholine receptors. Journal of Neuroscience 30(41): 13808-13813.
Gao, M., K. Sossa, L. Song, L. Errington, L. W. Cummings, H. Hwang, D. Kuhl, P. Worley, and H.-K. Lee (2010) A specific requirement of Arc/Arg3.1 for visual experience-induced homeostatic synaptic plasticity in mouse primary visual cortex. Journal of Neuroscience 30: 7168-7178.
Jiang, B.*, S. Huang*, R. de Pasquale, D. Millman, L. Song, H.-K. Lee , T. Tsumoto, and A. Kirkwood (2010) The maturation of GABAergic transmission in visual cortex requires endocannabinoid-mediated LTD of inhibitory inputs during a critical period. Neuron 66: 248-259.
Lee, H.-K ., K. Takamiya, K. He, L. Song, and R. L. Huganir (2010) Specific roles of AMPA receptor subunit GluR1 (GluA1) phosphorylation sites in regulating synaptic plasticity in the CA1 region of hippocampus. Journal of Neurophysiology 103: 476-489.
He, K., L. Song, L. W. Cummings, J. Goldman, R. L. Huganir, and H.-K. Lee (2009) Stabilization of Ca2+-permeable AMPA receptors at perisynaptic sites by GluR1-S845 phosphorylation. Proceedings of National Academy of Sciences USA 106(47): 20033-20038.
Chung, H. J. and H.-K. Lee (2009) Constructing a road map from synapses to behavior. EMBO Reports 10 (9): 958-962.
Wang, H., L. Song, F. M. Laird, P. C. Wong, and H.-K. Lee(2008) BACE1 knock-outs display deficits in activity-dependent potentiation of synaptic transmission at mossy fiber to CA3 synapses in the hippocampus. Journal of Neuroscience 28: 8677-8681.
Crombag, H. S., J. M. Sutton, K. Takamiya, H.-K. Lee, P. C. Holland, M. Gallagher, and R. L. Huganir (2008) A necessary role for GluR1 serine 831 phosphorylation in appetitive incentive learning. Behavioural Brain Research 191: 178-183.
Lee, H.-K. and R. L. Huganir (2008) AMPA receptor regulation and the reversal of synaptic plasticity - LTP, LTD, depotentiation, and dedepression. In: Comprehensive Handbook of Learning and Memory (Chief Editor: J. Byrne, Volume Editor: J. D. Sweatt), Elsevier press.
Seol, G. H., J. Ziburkus, S. Huang, L. Song, I. T. Kim, K. Takamiya, R. L. Huganir, H.-K. Lee, and A. Kirkwood (2007) Neuromodulators control the polarity of spike-timing-dependent synaptic plasticity. Neuron 55: 919-929.
Lee, H.-K., K. Takamiya, K. Kameyama, K. He, S. Yu , L. Rossetti, D. Wilen, and R. L. Huganir (2007) Identification and characterization of a novel phosphorylation site on the GluR1 subunit of AMPA receptors. Molecular and Cellular Neuroscience.
Goel, A. and H.-K. Lee (2007) Persistence of experience-induced homeostatic synaptic plasticity through adulthood in superficial layers of mouse visual cortex. Journal of Neuroscience 27 (25): 6692-6700.
Laird, F. M., M. H. Farah, H.-K. Lee, A. V. Savonenko, D. L. Price, and P. C. Wong (2007) Beta-secretase: Physiological Role and Target Validation. In: Alzheimer's Disease (Editors: S. S. Sisodia and R. E. Tanzi). Springer.
Goel, A., B. Jiang , L.W. Xu , L. Song ,A. Kirkwood , and H.-K. Lee(2006) Cross-modal regulation of synaptic AMPA receptors in primary sensory cortices by visual experience. Nature Neuroscience 9 (8): 1001-1003.
Lee, H.-K. (2006) AMPA receptor phosphorylation in synaptic plasticity: Insights from knockin mice. In: The Dynamic Synapse: Molecular methods in ionotropic receptor biology(Editors: J. Kittler and S. J. Moss). CRC press.
Laird, F. M., H. Cai, A. V. Savonenko,M. H. Farah, K. He, T. Melnikova, H. Wen, H.-C. Chiang, G. Xu, V. E. Koliatsos, D. R. Borchelt, D. L. Price, H.-K. Lee, and P. C. Wong(2005) BACE1, a major determinant of selective vulnerability of the brain to amyloid- amyloidogenesis, is essential for cognitive, emotional, and synaptic functions. Journal of Neuroscience, 25(50):11693-11709.
Lee, H.-K., S. S. Min, M. Gallagher, and A. Kirkwood(2005) NMDA receptor-independent long-term depression correlates with successful aging in rats. Nature Neuroscience 8: 1657-1659.
Hayashi, M. L., S.-Y. Choi, B. S. S. Rao, H.-Y. Jung, H.-K. Lee, D. Zhang, S. Chattarji, A. Kirkwood, and S. Tonegawa (2004) Altered cortical synaptic morphology and impaired memory consolidation in forebrain-specific dominant-negative PAK transgenic mice. Neuron 42: 757-771.
Lee, H.-K., K. Takamiya, J.-S. Han, H. Man, C.-H. Kim, G. Rumbaugh, S. Yu, C. He, L. Ding, R. S. Petralia, R. J. Wenthold, M. Gallagher, and R. L. Huganir (2003) Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory. Cell 112: 631-643.
Kim, J. H., H.-K. Lee, K. Takamiya, R. L. Huganir (2003) The role of Synaptic GTPase-Activating Protein in neuronal development and synaptic plasticity. Journal of Neuroscience 23: 1119-1124.
Chao, S. Z., W. Lu, H.-K. Lee, R. L. Huganir, and M. E. Wolf (2002) D1 dopamine receptor stimulation increases GluR1 phosphorylation in postnatal nucleus accumbens cultures. Journal of Neurochemistry 81: 984-992.
Choi, S.-Y., B. Morales, H.-K. Lee, and A. Kirkwood (2002) Long-term depression is reduced in the visual cortex of GAD65 knockout mice. Journal of Neuroscience 22: 5271-5276.
Kim, C.-H., H. J. Chung,, H.-K. Lee, J. Xia and R. L. Huganir (2001) Interaction of the AMPA receptor subunit GluR2/3 with PDZ domains regulates hippocampal long-term depression. Proceedings in National Academy of Sciences USA 98: 11725-11730.
Lee, H.-K. , M. Barbarosie, K. Kameyama, M. F. Bear and R. L. Huganir (2000) Regulation of distinct AMPA receptor phosphorylation sites during bi-directional synaptic plasticity. Nature 405: 955-959.
Banke, T. G., D. Bowie, H.-K. Lee, R. L. Huganir, A. Schousboe, and S. F. Traynelis (2000) Control of GluR1 AMPA receptor function by cAMP-dependent protein kinase and calcineurin. Journal of Neuroscience 20: 89-102.
Lee, H.-K. and R. L. Huganir (1999) Phosphorylation of glutamate receptors. In: Handbook of Experimental Pharmacology: Ionotropic Glutamate Receptors in the CNS(Editors: P. Jonas and H. Monyer). Springer-Verlag, Heidelberg.
Lee, H.-K., K. Kameyama, R. L. Huganir and M. F. Bear (1998) NMDA induces long-term synaptic depression and dephosphorylation of the GluR1 subunit of AMPA receptors in hippocampus. Neuron 21: 1151-1162.
Kameyama, K., H.-K. Lee, M. F. Bear and R. L. Huganir (1998) Involvement of a postsynaptic protein kinase A substrate in the expression of homosynaptic long-term depression. Neuron 21: 1163-1175.
Kirkwood, A., H.-K. Lee and M. F. Bear (1995) Co-regulation of long-term potentiation and experience-dependent plasticity in visual cortex by age and experience. Nature 375:328-331.
Selig, D. K., H.-K. Lee, M. F. Bear and R. C. Malenka (1995) Reexamination of the effects of MCPG on hippocampal LTP, LTD, and depotentiation. Journal of Neurophysiology 74 (3): 1075-1082.