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Senior Investigator

Katherine W. Roche, Ph.D.

Receptor Biology Section

Building 35 Room 2C-903
35 Convent Drive MSC 3704
Bethesda MD 20892-3704
Office: (301) 496-3800

Fax: (301) 480-4186

Dr. Roche received her B.S. from Duke University. In 1995 she received her Ph.D. from Johns Hopkins University, where she worked with Richard Huganir studying the regulation of glutamate receptors. She then did a postdoctoral fellowship with Robert Wenthold in the NIDCD, where she investigated the cell biology of glutamate receptor transport and localization. Dr. Roche joined NINDS as an Investigator in 2001. The main focus of her laboratory is the study of neurotransmitter receptor expression and targeting to the synapse.

Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system, and in addition to its central role in fast excitatory signaling it is also involved in synaptogenesis, synaptic plasticity, and the pathogenesis of certain neurologic diseases. Although glutamate acts as a neurotransmitter in all pathways of the central nervous system, the response to glutamate is not uniform at all glutamatergic synapses and varies with the type of glutamate receptor expressed on the postsynaptic membrane. In this context, we are interested in studying synapse-specific expression of postsynaptic NMDA and metabotropic glutamate receptors. My laboratory characterizes the molecular mechanisms underlying neurotransmitter receptor transport and localization at the synapse using several research strategies which include (1) defining sorting motifs present in neurotransmitter receptor cytosolic domains, (2) isolating neurotransmitter receptor-associated proteins, and (3) determining the role of protein-protein interactions in trafficking and specific synapse localization. Using these cell biological approaches, we hope to elucidate the mechanisms of neurotransmitter receptor trafficking in neurons and the role of accessory proteins at central synapses.

Staff Image
  • John Badger, M.S.
    Laboratory Manager

  • Elena Bagatelas, B.S.
    Post baccalaureate Fellow

  • Kai Chang, M.D.

  • Erin Fingleton, B.S.
    Post baccalaureate Fellow

  • Jaehoon Jeong, Ph.D.
    Postdoctoral Fellow

  • Richa Lomash, Ph.D.
    Postdoctoral Fellow

  • Thien Nguyen, B.S.
    Graduate Student

  • Jeremiah Paskus, B.S.
    Graduate Student

  • Marta Vieira, Ph.D.
    Postdoctoral Fellow

  • Sehoon Won, Ph.D.
    Postdoctoral Fellow

  • 1) Bemben MA, Nguyen TA, Li Y, Wang T, Nicoll RA, Roche KW (2019)
  • Isoform-specific cleavage of neuroligin-3 reduces synapse strength.
  • Molecular Psychiatry, 24(1), 145-160
  • 2) Won S, Incontro S, Li Y, Nicoll RA, Roche KW (2019)
  • The STEP61 interactome reveals subunit-specific AMPA receptor binding and synaptic regulation.
  • PNAS, 116(16), 8028-8037
  • 3) Liu S, Zhou L, Yuan H, Vieira M, Sanz-Clemente A, Badger JD 2nd, Lu W, Traynelis SF, Roche KW (2017)
  • A Rare Variant Identified Within the GluN2B C-Terminus in a Patient with Autism Affects NMDA Receptor Surface Expression and Spine Density
  • J Neurosci., 37(15), 4093-4102
  • 4) Bemben MA, Nguyen QA, Wang T, Li Y, Nicoll RA, Roche KW (2015)
  • Autism-associated mutation inhibits protein kinase C-mediated neuroligin-4X enhancement of excitatory synapses.
  • PNAS, 112(8), 2551-6
  • 5) Bemben, M.A., Shipman, S.L., Hirai, T., Herring, B.E., Li, Y., Badger, J.D. 2nd, Nicoll, R.A., Diamond, J.S., and Roche, K.W. (2014)
  • CaMKII Phosphorylation of Neuroligin-1 Regulates Excitatory Synapses
  • Nat. Neurosci, 17, 56-64
  • 6) Sanz-Clemente, A., Gray, J.S., Ogilvie, K.A., Nicoll, R.A., and Roche, K.W. (2013)
  • Activated CaMKII Couples GluN2B and Casein Kinase 2 to Control Synaptic NMDA Receptors
  • Cell Reports, 3(3), 607-14
  • 7) Chen, B.S., Gray, J.A., Sanz-Clemente, A., Wei, Z., Thomas, E.V., Nicoll, R.A., and Roche, K.W. (2012)
  • SAP102 Mediates Synaptic Clearance of NMDA Receptors.
  • Cell Reports, 2(5), 1120-8
  • 8) Lussier, M.P., Herring, B.E., Nasu-Nishimura, Y., Neutzner, A., Karbowski, M., Youle, R.J., Nicoll, R.A. and Roche, K.W. (2012)
  • Ubiquitin Ligase RNF167 Regulates AMPA Receptor -Mediated Synaptic Transmission
  • PNAS, 109(47), 19426-31
  • 9) Sanz-Clemente, A., Nicoll, R.A., and Roche, K.W. (2012)
  • Diversity in NMDA Receptor Composition: Many Regulators, Many Consequences.
  • Neuroscientist, 19(1), 62-75
  • 10) Chen, B.S., Thomas, E.V., Sanz-Clemente, A., and Roche, K.W. (2011)
  • NMDA Receptor-Dependent Regulation of Dendritic Spine Morphology by SAP102 Splice Variants.
  • J. Neurosci., 31(1), 89-96
  • 11) Choi, K.Y., Chang, K., Pickel, J.M., Badger, J.D. 2nd, and Roche K.W. (2011)
  • Expression of the metabotropic glutamate receptor 5 (mGluR5) induces melanoma in transgenic mice.
  • PNAS, 108 (37), 15219-24
  • 12) Nasu-Nishimura, Y., Jaffe, H., Isaac, J.T., and Roche, K.W. (2010)
  • Differential regulation of kainate receptor trafficking by phosphorylation of distinct sites on GluR6
  • J. Biol. Chem., 285(4), 2847-56
  • 13) Suh, Y.H., Terashima, A., Petralia, R.S., Wenthold, R.J., Isaac, J.T., Roche, K.W., and Roche, P.A. (2010)
  • A neuronal role for SNAP-23 in postsynaptic glutamate receptor trafficking
  • Nat. Neurosci.
  • 14) Sanz-Clemente, A., Matta, J.A., Isaac, J.T.R., and Roche, K.W. (2010)
  • Casein Kinase 2 Regulates the NR2 Subunit Composition of Synaptic NMDA Receptors
  • Neuron
  • 15) Chen, B.S. and Roche, K.W. (2009)
  • Growth Factor-Dependent Trafficking of Cerebellar NMDA Receptors Via Protein Kinase B/Akt Phosphorylation of NR2C
  • Neuron, 62, 471-8
  • 16) Lee, J.H., Lee, J., Choi, K.Y., Hepp, R., Lee J.Y., Lim, M.K., Chatani-Hinze, M., Kim, D.G., Ahn, Y.S., Kim, C.H., and Roche, K.W. (2008)
  • Calmodulin Dynamically Regulates the Trafficking of the Metabotropic Glutamate Receptor mGluR5
  • PNAS, 105, 12575-80
  • 17) Suh, Y.H., Pelkey, K.A., Lavezzari, G., Roche, P.A., Huganir, R.L., McBain, C.J., and Roche, K.W. (2008)
  • Co-Requirement of PICK1 Binding and PKC Phosphorylation for Stable Surface Expression of the Metabotropic Glutamate Receptor mGluR7
  • Neuron, 58, 736-48
  • 18) Nasu-Nishimura, Y., Hurtado, D., Braud, S., Tang, T.T., Isaac, J.T., and Roche, K.W. (2006)
  • Identification of an endoplasmic reticulum-retention motif in an intracellular loop of the kainate receptor subunit KA2
  • J. Neurosci., 26(26), 7014-21
  • 19) Chen, B.S., Braud, S., Badger, J.D. 2nd, Isaac, J.T., and Roche, K.W. (2006)
  • Regulation of NR1/NR2C N-methyl-D-aspartate (NMDA) receptors by phosphorylation
  • J. Biol. Chem., 281(24), 16583-90
  • 20) Kim, C.H., Braud, S., Isaac, J.T.R., and Roche, K.W. (2005)
  • PKC phosphorylation of the metabotropic glutamate receptor mGluR5 on serine 839 regulates Ca2+ oscillations
  • J. Biol. Chem., 280(27), 25409-15
  • 21) Pelkey, K.A., Lavezzari, G., Racca, C., Roche, K.W., and McBain, C.J. (2005)
  • mGluR7 is a metaplastic switch controllling bi-directional plasticity of feedforward inhibition
  • Neuron, 46, 89-102
  • 22) Roche, K.W. (2004)
  • The Expanding Role of PSD-95: A New Link to Addiction
  • Trends Neurosci., 27, 699-700
  • 23) Lavezzari, G., McCallum, J., Dewey, C. M., and Roche, K.W. (2004)
  • Subunit-Specific Regulation of NMDA Receptor Endocytosis
  • Journal of Neuroscience, 24(28), 6383-91
  • 24) Hayes D.M., Braud S., Hurtado D.E., McCallum J., Standley S., Isaac J.T.R., and Roche K.W. (2003)
  • Trafficking and surface expression of the glutamate receptor subunit, KA2
  • Biochem. Biophys. Res. Commun., 291, 85-90
  • 25) Lavezzari, G., McCallum, J., Lee, R., and Roche, K.W. (2003)
  • Differential binding of the AP-2 adaptor complex and PSD-95 to the C-terminus of the NMDA receptor subunit NR2B regulates surface expression
  • Neuropharmacology, 45, 729-737
  • 26) Roche, K.W., Standley, S., McCallum, J., Ly, C.D., Ehlers, M.D., and Wenthold, R.J. (2001)
  • Molecular Determinants of NMDA Receptor Internalization
  • Nature Neuroscience, 4, 794-802
  • 27) Standley, S., Roche, K.W., McCallum, J., Sans, N., and Wenthold, R.J. (2000)
  • PDZ-Domain Suppression of an ER Retention Signal in NMDA Receptor NR1 Splice Variants
  • Neuron, 28, 887-898
  • 28) Roche, K.W., Ly, C.D., Petralia, R.S., Wang, Y.X., McGee, A.W., Bredt, D.S., and Wenthold, R.J. (1999)
  • PSD-93 Interacts with the Delta 2 Glutamate Receptor Subunit at Parallel Fiber Synapses
  • J. Neurosc., 19, 3926-3934
  • 29) Roche, K.W., Tu, J.C., Petralia, R.S., Xiao, B., Wenthold, R.J., and Worley, P.F. (1999)
  • Homer 1b Regulates the Trafficking of Group I Metabotropic Glutamate Receptors
  • J. Biol. Chem., 274, 25953-25957
  • 30) Roche, K.W., O'Brien, R.J., Mammen, A.L., Bernhardt, J.P., and Huganir, R.L. (1996)
  • Characterization of Multiple Phosphorylation Sites on the AMPA Receptor GluR1 Subunit
  • Neuron, 16, 1179-1188
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