Derek Sieburth

Associate Professor,
Cell & Neurobiology
Zilkha Neurogenetic Institute
Keck School of Medicine of USC
PIBBS Mentor

Derek  Sieburth

Research Images

(a) Using fluorescence profiling to analyze presynaptic structure, (b) presynaptic compartments, (c) use of functional profiling across different conditions to identify related proteins

Research Overview

Intercellular signaling in the brain occurs at highly specialized subcellular structures called synapses. Synapses are surprisingly diverse in their structural and functional properties. For example, different synapses in the brain vary significantly in size, the number of neurotransmitter release sites, the pool of synaptic vesicles available for release and the probability of vesicle release. Beyond this diversity between synapses, the properties of each synapse are highly dynamic. This plasticity in synaptic properties is thought to underlie the specificity of neuronal wiring during development, and processes such as learning and memory. Synapses are biochemically complex structures composed of hundreds of different proteins. However, very little is known about the changes in molecular composition and signal transduction properties that underlie the diversity of synaptic function.

The Sieburth lab studies synaptic signaling pathways that regulate synaptic function, with the goal of understanding how these pathways contribute to the function of neuronal circuits controlling behavioral programs in the nervous system. My laboratory uses C. elegans as a model organism for studying synaptic biology, because of its simple neuronal circuitry, the ability to visualize synapses by fluorescent imaging in live animals, and its powerful genetics. We combine state of-the-art behavioral, genetic, cell biological, and in vivo neuronal imaging techniques in to study the cellular molecular mechanisms underlying secretion of synaptic vesicles and dense core vesicles. My lab is interested in three major areas: 1) How does localized sphingolipid signaling at presynaptic terminals regulate synaptic transmission at neuromuscular junctions, 2) The mechanisms by which oxidative stress regulates synaptic transmission and behavior, and 3) How does a neuropeptide signaling pathway deliver timing information from a pacemaker to activate a rhythmic behavioral circuit.

Contact Information

Mailing Address 2821 HSC
Office Location ZNI 327
Office Phone (323) 442-2013
Lab Location ZNI 219
Lab Phone
Office Location ZNI 327



  • Ph.D. University of Colorado
  • Postdoctoral research: Massachusetts General Hospital, Harvard Medical School

Selected Publications

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  • Staab T, Egrafov I, Knowles J, and Sieburth D. Regulation of Neuronal nlg-1/Neuroligin Expression by the skn-1/Nrf Stress Response Pathway Protects against Oxidative Stress in C. elegans. PLoS Genetics 2014 (In Press)

  • Wang H and Sieburth D. PKA Controls Calcium Influx into Motor Neurons during a Rhythmic Behavior. PLoS Genetics 2013 (In Press)

  • Chan JP, Staab TA, Wang H, Mazzasette C, Sieburth D. Extrasynaptic Muscarinic Acetylcholine Receptors on Neuronal Cell Bodies Regulate Presynaptic Function in C. elegans. J Neurosci. 2013 (In Press)

  • Wang H, Girskis K, Janssen T, Chan JP, Dasgupta K, Knowles JA, Schoofs L, and Sieburth D. Neuropeptide Secreted from a Pacemaker Activates Neurons to Control a Rhythmic Behavior. Current Biology 2013 May 6;23(9):746-54

    PubMed Link
  • Staab TA, Griffen TC, Corcoran C, Evgrafov O, Knowles JA, Sieburth D. The conserved SKN-1/Nrf2 stress response pathway regulates synaptic function in Caenorhabditis elegans. PLoS Genet. 2013 Mar;9(3):e1003354

    PubMed Link
  • Pickering AM, Staab TA, Tower J, Sieburth D, Davies KJ. A conserved role for the 20S proteasome and Nrf2 transcription factor in oxidative stress adaptation in mammals, Caenorhabditis elegans and Drosophila melanogaster. J Exp Biol. 2013 Feb 15;216(Pt 4):543-53

    PubMed Link
  • Chan JP, Sieburth D. Localized sphingolipid signaling at presynaptic terminals is regulated by calcium influx and promotes recruitment of priming factors.  J Neurosci. 2012 Dec 5;32(49):17909-20

    PubMed Link
  • Chan JP, Hu Z, and Sieburth D. Recruitment of sphingosine kinase to presynaptic terminals by a conserved muscarinic signaling pathway promotes neurotransmitter release. Genes Dev. 2012 May 15;26(10):1070-85. PubMed
  • Bedrood S,Jayasinghe S,Sieburth D,Chen M,Erbel S,Butler PC,Langen R,Ritzel RA - Annexin A5 directly interacts with amyloidogenic proteins and reduces their toxicity. Biochemistry [2009] Nov 10;48(44):10568-76 Link
  • Sieburth D, Ch'ng Q, Dybbs M, Tavazoie M, Kennedy S, Wang D, Dupuy D, Rual JF, Hill DE, Vidal M, Ruvkun G, Kaplan JM. (2005) Systematic analysis of genes required for synapse structure and function. Nature. 436(7050):510-7. PubMed