Ege Taner Kavalali, Ph.D.

Professor

ege.kavalali@vanderbilt.edu

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Faculty Appointments
Chair, Department of Pharmacology Professor of Pharmacology Professor of Biological SciencesWilliam Stokes Chair in Experimental Therapeutics
Education
Ph.D., Biomedical Engineering, Rutgers University, New Brunswick, New JerseyB.S., Electrical Engineeering, Bogazici University, Istanbul, Turkey
Office Address
465 21st Avenue South, 7130A MRBIII
Nashville, TN 37240
Research Description
As an undergraduate Dr. Kavalali studied Electrical Engineering at Bogazici University in Istanbul, Turkey. In 1995, he received his Ph.D. degree from Rutgers University, where he worked with Dr. Mark Plummer. In 1999, he completed his postdoctoral studies with Dr. Richard W. Tsien in Stanford University at the Department of Molecular and Cellular Physiology. The same year, Dr. Kavalali joined the faculty at the Center for Basic Neuroscience at UT Southwestern led by Dr. Thomas C. Südhof. After 19 years of service at UT Southwestern, in September 2018, Dr. Kavalali joined the Department of Pharmacology at Vanderbilt University as a Professor.

Dr. Kavalali studies mechanisms of neurotransmission and synaptic signaling in the central nervous system using electrical and optical recording techniques as well as molecular tools. His group focuses on the molecular basis and functional consequences of heterogeneity among synaptic vesicle recycling pathways present within individual synapses. In particular, his work has uncovered the role and underlying mechanisms of spontaneous neurotransmitter release that holds it apart mechanistically and functionally from evoked neurotransmission. These studies gave rise to the hypothesis that spontaneous neurotransmission acts as an autonomous neuronal signaling pathway independent of action potential-evoked synaptic transmission. In addition, Dr. Kavalali and colleagues have identified spontaneous neurotransmission-dependent signal transduction mechanisms that are required to trigger rapid antidepressant action.
Research Keywords
Electrophysiology, Mechanisms of Rapid Antidepressant Action, Neurotransmitter Release, Synaptic Transmission and Plasticity
Publications
Kim JW, Suzuki K, Kavalali ET, Monteggia LM. Ketamine: Mechanisms and Relevance to Treatment of Depression. Annu Rev Med [print-electronic]. 2023 Sep 9/20/2023; PMID: 37729028, DOI: 10.1146/annurev-med-051322-120608, ISSN: 1545-326X.

Krystal JH, Kavalali ET, Monteggia LM. Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms. Neuropsychopharmacology [print-electronic]. 2023 Jul 7/24/2023; PMID: 37488280, PII: 10.1038/s41386-023-01629-w, DOI: 10.1038/s41386-023-01629-w, ISSN: 1740-634X.

Kim JW, Suzuki K, Kavalali ET, Monteggia LM. Bridging rapid and sustained antidepressant effects of ketamine. Trends Mol Med [print-electronic]. 2023 May; 29(5): 364-75. PMID: 36907686, PMCID: PMC10101916, PII: S1471-4914(23)00035-7, DOI: 10.1016/j.molmed.2023.02.003, ISSN: 1471-499X.

Kavalali ET. Interrogating synaptic transmission at circadian time scales. J Physiol [print-electronic]. 2023 May; 601(10): 1697-8. PMID: 36994489, DOI: 10.1113/JP284668, ISSN: 1469-7793.

Guzikowski NJ, Kavalali ET. Super-resolution imaging of synaptic scaffold proteins in rat hippocampal neurons. STAR Protoc [print-electronic]. 2023 Feb 2/2/2023; 4(1): 102080. PMID: 36853692, PMCID: PMC9932186, PII: S2666-1667(23)00038-2, DOI: 10.1016/j.xpro.2023.102080, ISSN: 2666-1667.

Uzay B, Houcek A, Ma ZZ, Konradi C, Monteggia LM, Kavalali ET. Neurotransmitter release progressively desynchronizes in induced human neurons during synapse maturation and aging. Cell Rep [print-electronic]. 2023 Jan 1/25/2023; 42(2): 112042. PMID: 36701235, PII: S2211-1247(23)00053-0, DOI: 10.1016/j.celrep.2023.112042, ISSN: 2211-1247.

Jaczynska K, Esquivies L, Pfuetzner RA, Alten B, Brewer KD, Zhou Q, Kavalali ET, Brunger AT, Rizo J. Analysis of tripartite Synaptotagmin-1-SNARE-complexin-1 complexes in solution. FEBS Open Bio [print-electronic]. 2023 Jan; 13(1): 26-50. PMID: 36305864, PMCID: PMC9811660, DOI: 10.1002/2211-5463.13503, ISSN: 2211-5463.

Uzay B, Kavalali ET. Genetic disorders of neurotransmitter release machinery. Front Synaptic Neurosci. 2023; 15: 1148957. PMID: 37066095, PMCID: PMC10102358, DOI: 10.3389/fnsyn.2023.1148957, ISSN: 1663-3563.

Alten B, Guzikowski NJ, Zurawski Z, Hamm HE, Kavalali ET. Presynaptic mechanisms underlying GABAB-receptor-mediated inhibition of spontaneous neurotransmitter release. Cell Rep. 2022 Jan 1/18/2022; 38(3): 110255. PMID: 35045279, PMCID: PMC8793855, PII: S2211-1247(21)01767-8, DOI: 10.1016/j.celrep.2021.110255, ISSN: 2211-1247.

Wang CS, Kavalali ET, Monteggia LM. BDNF signaling in context: From synaptic regulation to psychiatric disorders. Cell [print-electronic]. 2022 Jan 1/6/2022; 185(1): 62-76. PMID: 34963057, PMCID: PMC8741740, PII: S0092-8674(21)01425-2, DOI: 10.1016/j.cell.2021.12.003, ISSN: 1097-4172.

Suzuki K, Kim JW, Nosyreva E, Kavalali ET, Monteggia LM. Convergence of distinct signaling pathways on synaptic scaling to trigger rapid antidepressant action. Cell Rep. 2021 Nov 11/2/2021; 37(5): 109918. PMID: 34731624, PMCID: PMC8590465, PII: S2211-1247(21)01391-7, DOI: 10.1016/j.celrep.2021.109918, ISSN: 2211-1247.

Chanaday NL, Kavalali ET. Synaptobrevin-2 dependent regulation of single synaptic vesicle endocytosis. Mol Biol Cell [print-electronic]. 2021 Sep 9/1/2021; 32(19): 1818-23. PMID: 34191540, DOI: 10.1091/mbc.E21-04-0213, ISSN: 1939-4586.

Lin PY, Ma ZZ, Mahgoub M, Kavalali ET, Monteggia LM. A synaptic locus for TrkB signaling underlying ketamine rapid antidepressant action. Cell Rep. 2021 Aug 8/17/2021; 36(7): 109513. PMID: 34407417, PMCID: PMC8404212, PII: S2211-1247(21)00943-8, DOI: 10.1016/j.celrep.2021.109513, ISSN: 2211-1247.

Horvath PM, Chanaday NL, Alten B, Kavalali ET, Monteggia LM. A subthreshold synaptic mechanism regulating BDNF expression and resting synaptic strength. Cell Rep. 2021 Aug 8/3/2021; 36(5): 109467. PMID: 34348149, PMCID: PMC8371576, PII: S2211-1247(21)00890-1, DOI: 10.1016/j.celrep.2021.109467, ISSN: 2211-1247.

Kim JW, Autry AE, Na ES, Adachi M, Björkholm C, Kavalali ET, Monteggia LM. Sustained effects of rapidly acting antidepressants require BDNF-dependent MeCP2 phosphorylation. Nat Neurosci [print-electronic]. 2021 Aug; 24(8): 1100-9. PMID: 34183865, PMCID: PMC8338784, PII: 10.1038/s41593-021-00868-8, DOI: 10.1038/s41593-021-00868-8, ISSN: 1546-1726.

Kim JW, Herz J, Kavalali ET, Monteggia LM. A key requirement for synaptic Reelin signaling in ketamine-mediated behavioral and synaptic action. Proc Natl Acad Sci U S A. 2021 May 5/18/2021; 118(20): PMID: 33975959, PMCID: PMC8157952, PII: 2103079118, DOI: 10.1073/pnas.2103079118, ISSN: 1091-6490.

Shin OH, Kavalali ET. Evolutionary diversity of the dual Ca2+ sensor system for neurotransmitter release. Cell Calcium [print-electronic]. 2021 Mar 3/26/2021; 96: 102402. PMID: 33813181, PII: S0143-4160(21)00056-7, DOI: 10.1016/j.ceca.2021.102402, ISSN: 1532-1991.

Vilcaes AA, Chanaday NL, Kavalali ET. Interneuronal exchange and functional integration of synaptobrevin via extracellular vesicles. Neuron [print-electronic]. 2021 Mar 3/17/2021; 109(6): 971-983.e5. PMID: 33513363, PMCID: PMC7979516, PII: S0896-6273(21)00007-6, DOI: 10.1016/j.neuron.2021.01.007, ISSN: 1097-4199.

Chanaday NL, Nosyreva E, Shin OH, Zhang H, Aklan I, Atasoy D, Bezprozvanny I, Kavalali ET. Presynaptic store-operated Ca2+ entry drives excitatory spontaneous neurotransmission and augments endoplasmic reticulum stress. Neuron [print-electronic]. 2021 Mar 3/4/2021; PMID: 33711258, PII: S0896-6273(21)00123-9, DOI: 10.1016/j.neuron.2021.02.023, ISSN: 1097-4199.

Alten B, Zhou Q, Shin OH, Esquivies L, Lin PY, White KI, Sun R, Chung WK, Monteggia LM, Brunger AT, Kavalali ET. Role of Aberrant Spontaneous Neurotransmission in SNAP25-Associated Encephalopathies. Neuron [print-electronic]. 2021 Jan 1/6/2021; 109(1): 59-72.e5. PMID: 33147442, PMCID: PMC7790958, PII: S0896-6273(20)30808-4, DOI: 10.1016/j.neuron.2020.10.012, ISSN: 1097-4199.

Guzikowski NJ, Kavalali ET. Nano-Organization at the Synapse: Segregation of Distinct Forms of Neurotransmission. Front Synaptic Neurosci. 2021; 13: 796498. PMID: 35002671, PMCID: PMC8727373, DOI: 10.3389/fnsyn.2021.796498, ISSN: 1663-3563.

Simmons RL, Li H, Alten B, Santos MS, Jiang R, Paul B, Lalani SJ, Cortesi A, Parks K, Khandelwal N, Smith-Packard B, Phoong MA, Chez M, Fisher H, Scheuerle AE, Shinawi M, Hussain SA, Kavalali ET, Sherr EH, Voglmaier SM. Overcoming presynaptic effects of VAMP2 mutations with 4-aminopyridine treatment. Hum Mutat [print-electronic]. 2020 Nov; 41(11): 1999-2011. PMID: 32906212, DOI: 10.1002/humu.24109, ISSN: 1098-1004.

Lin PY, Chanaday NL, Horvath PM, Ramirez DMO, Monteggia LM, Kavalali ET. VAMP4 maintains a Ca2+-sensitive pool of spontaneously recycling synaptic vesicles. J. Neurosci [print-electronic]. 2020 Jun 6/12/2020; PMID: 32532887, PII: JNEUROSCI.2386-19.2020, DOI: 10.1523/JNEUROSCI.2386-19.2020, ISSN: 1529-2401.

Kavalali ET, Monteggia LM. Targeting Homeostatic Synaptic Plasticity for Treatment of Mood Disorders. Neuron. 2020 Jun 6/3/2020; 106(5): 715-26. PMID: 32497508, PII: S0896-6273(20)30361-5, DOI: 10.1016/j.neuron.2020.05.015, ISSN: 1097-4199.

Horvath PM, Piazza MK, Monteggia LM, Kavalali ET. Spontaneous and evoked neurotransmission are partially segregated at inhibitory synapses. Elife. 2020 May 5/13/2020; 9: PMID: 32401197, PMCID: PMC7250572, PII: 52852, DOI: 10.7554/eLife.52852, ISSN: 2050-084X.

Chanaday NL, Kavalali ET. Is Ca2+ Essential for Synaptic Vesicle Endocytosis?. Trends Neurosci [print-electronic]. 2020 Feb; 43(2): 77-9. PMID: 31910996, PII: S0166-2236(19)30223-1, DOI: 10.1016/j.tins.2019.12.001, ISSN: 1878-108X.

Bezprozvanny I, Kavalali ET. Presynaptic endoplasmic reticulum and neurotransmission. Cell Calcium [print-electronic]. 2020 Jan; 85: 102133. PMID: 31812114, PII: S0143-4160(19)30202-7, DOI: 10.1016/j.ceca.2019.102133, ISSN: 1532-1991.

Monteggia LM, Lin PY, Adachi M, Kavalali ET. Behavioral Analysis of SNAP-25 and Synaptobrevin-2 Haploinsufficiency in Mice. Neuroscience [print-electronic]. 2019 Nov 11/10/2019; 420: 129-35. PMID: 30144509, PMCID: PMC6387657, PII: S0306-4522(18)30559-1, DOI: 10.1016/j.neuroscience.2018.08.014, ISSN: 1873-7544.

Hoerder-Suabedissen A, Korrell KV, Hayashi S, Jeans A, Ramirez DMO, Grant E, Christian HC, Kavalali ET, Wilson MC, Molnár Z. Cell-Specific Loss of SNAP25 from Cortical Projection Neurons Allows Normal Development but Causes Subsequent Neurodegeneration. Cereb. Cortex. 2019 May 5/1/2019; 29(5): 2148-59. PMID: 29850799, PMCID: PMC6754517, PII: 5025424, DOI: 10.1093/cercor/bhy127, ISSN: 1460-2199.

Kavalali ET. Neuronal Ca2+ signalling at rest and during spontaneous neurotransmission. J. Physiol. (Lond.) [print-electronic]. 2019 Feb 2/8/2019; PMID: 30735245, DOI: 10.1113/JP276541, ISSN: 1469-7793.

Chanaday NL, Kavalali ET. Time course and temperature dependence of synaptic vesicle endocytosis. FEBS Lett [print-electronic]. 2018 Nov; 592(21): 3606-14. PMID: 30311950, DOI: 10.1002/1873-3468.13268, ISSN: 1873-3468.

Lin PY, Kavalali ET, Monteggia LM. Genetic Dissection of Presynaptic and Postsynaptic BDNF-TrkB Signaling in Synaptic Efficacy of CA3-CA1 Synapses. Cell Rep. 2018 Aug 8/7/2018; 24(6): 1550-61. PMID: 30089265, PII: S2211-1247(18)31110-0, DOI: 10.1016/j.celrep.2018.07.020, ISSN: 2211-1247.

Chanaday NL, Kavalali ET. Presynaptic origins of distinct modes of neurotransmitter release. Curr. Opin. Neurobiol [print-electronic]. 2018 Aug; 51: 119-26. PMID: 29597140, PMCID: PMC6066415, PII: S0959-4388(17)30286-6, DOI: 10.1016/j.conb.2018.03.005, ISSN: 1873-6882.

Liu P, Khvotchev M, Li YC, Chanaday NL, Kavalali ET. Copine-6 Binds to SNAREs and Selectively Suppresses Spontaneous Neurotransmission. J. Neurosci [print-electronic]. 2018 Jun 6/27/2018; 38(26): 5888-99. PMID: 29802203, PMCID: PMC6021993, PII: JNEUROSCI.0461-18.2018, DOI: 10.1523/JNEUROSCI.0461-18.2018, ISSN: 1529-2401.

Chanaday NL, Kavalali ET. Optical detection of three modes of endocytosis at hippocampal synapses. Elife. 2018 Apr 4/23/2018; 7: PMID: 29683423, PMCID: PMC5959719, PII: 36097, DOI: 10.7554/eLife.36097, ISSN: 2050-084X.

Kavalali ET. Spontaneous neurotransmission: A form of neural communication comes of age. J. Neurosci. Res [print-electronic]. 2018 Mar; 96(3): 331-4. PMID: 29219198, PMCID: PMC5766395, DOI: 10.1002/jnr.24207, ISSN: 1097-4547.

Ramirez DMO, Crawford DC, Chanaday NL, Trauterman B, Monteggia LM, Kavalali ET. Loss of Doc2-Dependent Spontaneous Neurotransmission Augments Glutamatergic Synaptic Strength. J. Neurosci [print-electronic]. 2017 Jun 6/28/2017; 37(26): 6224-30. PMID: 28539418, PMCID: PMC5490061, PII: JNEUROSCI.0418-17.2017, DOI: 10.1523/JNEUROSCI.0418-17.2017, ISSN: 1529-2401.

Suzuki K, Nosyreva E, Hunt KW, Kavalali ET, Monteggia LM. Effects of a ketamine metabolite on synaptic NMDAR function. Nature. 2017 Jun 6/21/2017; 546(7659): E1-E3. PMID: 28640258, PII: nature22084, DOI: 10.1038/nature22084, ISSN: 1476-4687.

Li YC, Kavalali ET. Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets. Pharmacol. Rev. 2017 Apr; 69(2): 141-60. PMID: 28265000, PMCID: PMC5394918, PII: 69/2/141, DOI: 10.1124/pr.116.013342, ISSN: 1521-0081.

Crawford DC, Ramirez DM, Trauterman B, Monteggia LM, Kavalali ET. Selective molecular impairment of spontaneous neurotransmission modulates synaptic efficacy. Nat Commun. 2017 Feb 2/10/2017; 8: 14436. PMID: 28186166, PMCID: PMC5311059, PII: ncomms14436, DOI: 10.1038/ncomms14436, ISSN: 2041-1723.

Li YC, Chanaday NL, Xu W, Kavalali ET. Synaptotagmin-1- and Synaptotagmin-7-Dependent Fusion Mechanisms Target Synaptic Vesicles to Kinetically Distinct Endocytic Pathways. Neuron [print-electronic]. 2017 Feb 2/8/2017; 93(3): 616-631.e3. PMID: 28111077, PMCID: PMC5300960, PII: S0896-6273(16)30949-7, DOI: 10.1016/j.neuron.2016.12.010, ISSN: 1097-4199.

Reese AL, Kavalali ET. Single synapse evaluation of the postsynaptic NMDA receptors targeted by evoked and spontaneous neurotransmission. Elife. 2016 Nov 11/24/2016; 5: PMID: 27882871, PMCID: PMC5148599, DOI: 10.7554/eLife.21170, ISSN: 2050-084X.

Reese AL, Kavalali ET. Spontaneous neurotransmission signals through store-driven Ca(2+) transients to maintain synaptic homeostasis. Elife. 2015 Jul 7/24/2015; 4: PMID: 26208337, PMCID: PMC4534843, DOI: 10.7554/eLife.09262, ISSN: 2050-084X.

Kavalali ET. The mechanisms and functions of spontaneous neurotransmitter release. Nat. Rev. Neurosci. 2015 Jan; 16(1): 5-16. PMID: 25524119, PII: nrn3875, DOI: 10.1038/nrn3875, ISSN: 1471-0048.

Leitz J, Kavalali ET. Fast retrieval and autonomous regulation of single spontaneously recycling synaptic vesicles. Elife. 2014 Nov 11/21/2014; 3: e03658. PMID: 25415052, PMCID: PMC4270043, DOI: 10.7554/eLife.03658, ISSN: 2050-084X.

Gideons ES, Kavalali ET, Monteggia LM. Mechanisms underlying differential effectiveness of memantine and ketamine in rapid antidepressant responses. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2014 Jun 6/10/2014; 111(23): 8649-54. PMID: 24912158, PMCID: PMC4060670, PII: 1323920111, DOI: 10.1073/pnas.1323920111, ISSN: 1091-6490.

Kavalali ET, Jorgensen EM. Visualizing presynaptic function. Nat. Neurosci [print-electronic]. 2014 Jan; 17(1): 10-6. PMID: 24369372, PII: nn.3578, DOI: 10.1038/nn.3578, ISSN: 1546-1726.

Bal M, Leitz J, Reese AL, Ramirez DM, Durakoglugil M, Herz J, Monteggia LM, Kavalali ET. Reelin mobilizes a VAMP7-dependent synaptic vesicle pool and selectively augments spontaneous neurotransmission. Neuron [print-electronic]. 2013 Nov 11/20/2013; 80(4): 934-46. PMID: 24210904, PMCID: PMC3840105, PII: S0896-6273(13)00758-7, DOI: 10.1016/j.neuron.2013.08.024, ISSN: 1097-4199.

Nosyreva E, Szabla K, Autry AE, Ryazanov AG, Monteggia LM, Kavalali ET. Acute suppression of spontaneous neurotransmission drives synaptic potentiation. J. Neurosci. 2013 Apr 4/17/2013; 33(16): 6990-7002. PMID: 23595756, PMCID: PMC3661220, PII: 33/16/6990, DOI: 10.1523/JNEUROSCI.4998-12.2013, ISSN: 1529-2401.

Kavalali ET, Monteggia LM. Synaptic mechanisms underlying rapid antidepressant action of ketamine. Am J Psychiatry. 2012 Nov; 169(11): 1150-6. PMID: 23534055, DOI: 10.1176/appi.ajp.2012.12040531, ISSN: 1535-7228.