Derek S. Sieburth, PhD

The Sieburth lab studies signaling pathways that regulate neuronal 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 neuronal function, because of its simple neuronal circuitry, the ability to visualize synapses and neurotransmitters 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. The lab is interested in three major areas: 1) What are the molecular mechanisms underlying the regulation of neuropeptide storage and secretion from dense core vesicles? 2) What are the mechanisms by which oxidative stress regulates neurotransmitter secretion and stress responses, and 3) How does sphingolipid signaling control mitochondrial homeostasis in response to neuronal stress? Many of the genes we study are conserved in mammals, so our studies provide novel insight into the mechanisms by which neurotransmitter secretion may be regulated in humans.
To visit the Sieburth lab website go here: https://sites.usc.edu/sieburthlab/

• The head mesodermal cell couples FMRFamide neuropeptide signaling with rhythmic muscle contraction in Celegans. Nat Commun. 2023 07 14; 14(1):4218. . View in PubMed
• Mitochondrial hydrogen peroxide positively regulates neuropeptide secretion during diet-induced activation of the oxidative stress response Nat Commun. 2021 04 16; 12(1):2304. . View in PubMed
• Presynaptic coupling by electrical synapses coordinates a rhythmic behavior by synchronizing the activities of a neuron pair Proc Natl Acad Sci U S A. 2021 05 18; 118(20). . View in PubMed
• FSHR-1/GPCR Regulates the Mitochondrial Unfolded Protein Response in Caenorhabditis elegans Genetics. 2020 02; 214(2):409-418. . View in PubMed
• A Receptor Tyrosine Kinase Network Regulates Neuromuscular Function in Response to Oxidative Stress in Caenorhabditis elegans Genetics. 2019 04; 211(4):1283-1295. . View in PubMed
• Sphingosine Kinase Activates the Mitochondrial Unfolded Protein Response and Is Targeted to Mitochondria by StressCell Rep. 2018 09 11; 24(11):2932-2945. e4. . View in PubMed
• Sphingosine Kinase Regulates Neuropeptide Secretion During the Oxidative Stress-Response Through Intertissue Signaling J Neurosci. 2018 09 19; 38(38):8160-8176. . View in PubMed
• nu444 is a novel allele of pkc-1 in Celegans. MicroPubl Biol. 2017 May 18; 2017. . View in PubMed
• Aging and SKN-1-dependent Loss of 20S Proteasome Adaptation to Oxidative Stress in Celegans. J Gerontol A Biol Sci Med Sci. 2017 02; 72(2):143-151. . View in PubMed
• Coupling between endocytosis and sphingosine kinase 1 recruitment Nat Cell Biol. 2014 Jul; 16(7):652-62. . View in PubMed
• Regulation of synaptic nlg-1/neuroligin abundance by the skn-1/Nrf stress response pathway protects against oxidative stress PLoS Genet. 2014 Jan; 10(1):e1004100. . View in PubMed
• Extrasynaptic muscarinic acetylcholine receptors on neuronal cell bodies regulate presynaptic function in Caenorhabditis elegans J Neurosci. 2013 Aug 28; 33(35):14146-59. . View in PubMed
• Neuropeptide secreted from a pacemaker activates neurons to control a rhythmic behavior Curr Biol. 2013 May 06; 23(9):746-54. . View in PubMed
• The conserved SKN-1/Nrf2 stress response pathway regulates synaptic function in Caenorhabditis elegans PLoS Genet. 2013 Mar; 9(3):e1003354. . View in PubMed
• 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. . View in PubMed
• PKA controls calcium influx into motor neurons during a rhythmic behavior PLoS Genet. 2013; 9(9):e1003831. . View in PubMed
• Localized sphingolipid signaling at presynaptic terminals is regulated by calcium influx and promotes recruitment of priming factors J Neurosci. 2012 Dec 05; 32(49):17909-20. . View in PubMed
• 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. . View in PubMed
• RIC-7 promotes neuropeptide secretion PLoS Genet. 2012 Jan; 8(1):e1002464. . View in PubMed
• Annexin A5 directly interacts with amyloidogenic proteins and reduces their toxicity Biochemistry. 2009 Nov 10; 48(44):10568-76. . View in PubMed
• Profiling synaptic proteins identifies regulators of insulin secretion and lifespan PLoS Genet. 2008 Nov; 4(11):e1000283. . View in PubMed
• An RNAi screen identifies genes that regulate GABA synapses Neuron. 2008 May 08; 58(3):346-61. . View in PubMed
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• Systematic analysis of genes required for synapse structure and function Nature. 2005 Jul 28; 436(7050):510-7. . View in PubMed
• A PP2A regulatory subunit positively regulates Ras-mediated signaling during Caenorhabditis elegans vulval induction Genes Dev. 1999 Oct 01; 13(19):2562-9. . View in PubMed
• SUR-8, a conserved Ras-binding protein with leucine-rich repeats, positively regulates Ras-mediated signaling in Celegans. Cell. 1998 Jul 10; 94(1):119-30. . View in PubMed
• Interleukin-12 production by human monocytes infected with Mycobacterium tuberculosis: role of phagocytosis Infect Immun. 1996 Jul; 64(7):2523-31. . View in PubMed
• Resolution of cutaneous leishmaniasis: interleukin 12 initiates a protective T helper type 1 immune response J Exp Med. 1993 Jun 01; 177(6):1797-802. . View in PubMed

• Curran, Sean
• Davies, Kelvin
• Higuchi-Sanabria, Ryo
• Melov, Simon
• Mir, Dilawar