Columbia University Medical Center

DEPARTMENT OF NEUROSCIENCE

Clarissa Waites, PhD

Clarissa Waites, PhD
  • Department of Pathology & Cell Biology
  • Department of Neuroscience
  • Assistant Professor of Pathology and Cell Biology
  • Assistant Professor of Neuroscience (in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain)

Excitatory synapses in the central nervous system must simultaneously be plastic, in order to change their response properties over time, and stable, in order to persist for weeks to months, or even throughout an organism’s lifetime. Defects in either property can lead to neurodevelopmental or neurodegenerative disorders, severely compromising cognition and quality of life. My laboratory studies the molecular mechanisms underlying these two critical yet seemingly contradictory synaptic properties. Our focus is on protein ubiquitination, a post-translational modification that targets proteins for degradation and has less-understood roles in coordinating their trafficking and binding interactions. At synapses, “regulated” ubiquitination is implicated in synapse formation/stabilization, neurotransmitter release, and plasticity mechanisms, while “dysregulated” ubiquitination is linked to synapse destabilization/loss and the etiology of several devastating neurodegenerative diseases. Accordingly, our major areas of investigation are: 1) how ubiquitination regulates normal synaptic function, focusing on its roles in neurotransmitter release, 2) how the ubiquitin proteasome system and other degradative pathways (e.g. autophagy, ESCRT system) regulate protein degradation at the synapse, and 3) how imbalances in synaptic protein ubiquitination/degradation disrupt protein homeostasis and lead to neurodegeneration. To address these questions, we perform gain and loss-of-function studies in primary neuronal cultures and brain slices, using a sophisticated lentiviral delivery system, quantitative live-cell imaging, electrophysiology, and biochemistry.

Biography

Education & Training

  • BS, Biological Sciences, Stanford University
  • PhD, Neuroscience, University of California , San Francisco
  • Lab Locations

    William Black Building

    650 West 168th Street
    BB1212
    New York, NY 10032

    Phone:
    (212) 305-6025
    Email:
    cw2622@cumc.columbia.edu

    Teaching Responsibilities

    Synaptic Transmission

    Neurodevelopment

    Research Interests

    Neural Degeneration and Repair
    cellular/molecular/developmental neuroscience
    Neurobiology of Learning and Memory
    Synapses and circuits

    Lab Members

  • Alexandria Wise, postdoctoral researcher
  • Patricia Sheehan, graduate student
  • Anne Beskow, postdoctoral fellow
  • Cyndel Vollmer, graduate student
  • Giuseppe Cortese, postdoctoral researcher
  • Collaborators

    Dalibor Sames, Dept. of Chemistry.
    We are working with the Sames lab and the Columbia High-Throughput Screening facility to develop high-throughput screening platforms in order to identify novel fluorescent compounds that label synapses.

    Publications

    Waites CL, Leal-Ortiz SA, Okerlund N, Dalke H, Fejtova A, Altrock WD, Gundelfinger ED, Garner CC (2013) Bassoon and Piccolo maintain synapse integrity by regulating protein ubiquitination and degradation. EMBO J., 32(7):954-69.

    Waites CL, Garner CC (2011) Presynaptic function in health and disease. Trends Neurosci. 34(6): 326-37.

    Waites CL, Leal-Ortiz SA, Andlauer TFM, Sigrist SJ, Garner CC. (2011) Piccolo regulates the dynamic assembly of presynaptic F-Actin. J Neurosci. 31(40):14250-63.

    Li D, Specht CG, Waites CL, Butler-Munro C, Leal-Ortiz SA, Foote JW, Genoux D, Garner CC, Montgomery JM (2011) SAP97 directs NMDA receptor spine targeting and synaptic plasticity. J Physiol. 589(18):4491-510. 

    Hua Z, Leal-Ortiz SA, Foss SM, Waites CL, Garner CC, Voglmaier SM, and Edwards, RH (2011) v-SNARE composition distinguishes synaptic vesicle pools. Neuron. 71(3):474-87.

    Waites CL, Garner CC (2011) Presynaptic function in health and disease. Trends Neurosci. 34(6): 326-37. 

    Jeyifous O, Waites CL, Specht CG, Fujisawa S, Schubert M, Lin EI, Marshall J, Aoki C, de Silva T, Montgomery JM, Garner CC, Green WN (2009) SAP97 and CASK mediate sorting of NMDA receptors through a previously unknown secretory pathway. Nat Neurosci. 12(18):1011-9.

    Waites CL*, Specht CG* (*contributed equally), Haertel K, Leal-Ortiz S, Genoux D, Li D, Drisdel RC, Jeyifous O, Cheyne JE, Green WN, Montgomery JM, Garner CC (2009) Synaptic SAP97 isoforms regulate AMPA receptor dynamics and access to presynaptic glutamate. J Neurosci. 29(14):4332-4345.

    Leal-Ortiz S*, Waites CL* (*contributed equally), Terry-Lorenzo R, Zamorano P, Gundelfinger ED, Garner CC (2008) Piccolo modulation of Synapsin1a dynamics regulates synaptic vesicle exocytosis.  J Cell Biol. 181:831-846.

    Regalado MP, Terry-Lorenzo RT, Waites CL, Garner CC, Malenka RC (2006) Transsynaptic signaling by postsynaptic synapse-associated protein 97. J Neurosci. 26(8): 2343-57.

    Garner CC, Waites CL, Ziv NE (2006) Synapse development: still looking for the forest, still lost in the trees. Cell Tissue Res. 326:249-62. 

    Waites CL, Craig AM, Garner CC (2005) Mechanisms of vertebrate synaptogenesis. Ann Rev Neurosci. 28:251-74.