Derek Toomre, PhD
Professor of Cell BiologyCards
Appointments
Additional Titles
Director of the YALE 'CINEMA' Laboratory (Cellular Imaging using New Microscopy Approaches)
Contact Info
Cell Biology
PO Box 208002, 333 Cedar Street
New Haven, CT 06520-8002
United States
Appointments
Additional Titles
Director of the YALE 'CINEMA' Laboratory (Cellular Imaging using New Microscopy Approaches)
Contact Info
Cell Biology
PO Box 208002, 333 Cedar Street
New Haven, CT 06520-8002
United States
Appointments
Additional Titles
Director of the YALE 'CINEMA' Laboratory (Cellular Imaging using New Microscopy Approaches)
Contact Info
Cell Biology
PO Box 208002, 333 Cedar Street
New Haven, CT 06520-8002
United States
About
Titles
Professor of Cell Biology
Director of the YALE 'CINEMA' Laboratory (Cellular Imaging using New Microscopy Approaches)
Appointments
Cell Biology
ProfessorPrimary
Other Departments & Organizations
- Biochemistry, Quantitative Biology, Biophysics and Structural Biology (BQBS)
- Cancer Signaling Networks
- Cell Biology
- Cell Biology Research
- Cytoskeletal Dynamics
- Diabetes Research Center
- Membrane Traffic
- Molecular Cell Biology, Genetics and Development
- Yale Cancer Center
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- Yale Ventures
Education & Training
- PhD
- University of California, San Diego (1996)
- MS
- University of California, San Diego (1992)
Research
Overview
Cellular Imaging and Analysis of Polarized Membrane Traffic. A major goal of my laboratory is to develop and apply new and state-of-the-art multidimensional optical methods to better understand the basic mechanisms of polarized membrane trafficking and spatial-temporal control of endo-exocytosis.
One important challenge facing modern biology is to understand how individual biochemical reactions are integrated in space and time. Increasingly, new vital probes and optical methods has begun to provide unique mechanistic insight into how molecules, vesicles, organelles and whole cells are (re)organized in response to internal and external cues. This is especially relevant for the dynamic process of membrane traffic and the cytoskeleton in cell polarity - key areas of our interest. Insight into how cells both establish and lose polarity are also essential for understanding disease processes such as metastasis. In particular we are applying the optical methods of Total Internal Reflections Fluorescence Microscopy (TIRFM) and 4D (3D + time) multicolor spinning-disk confocal imaging to directly address, at the single-vesicle level, where and how polarized membrane traffic is delivered. TIRFM imaging (also called evanescent wave microscopy) can selectively illuminate an extremely thin optical section (
Specifically, using advance optical methods our lab is exploring the following related topics:
1) organization and coordination of exocytosis and cytoskeleton in polarized cells and
2) coupling of exo- and endocytosis and molecular mechanisms that regulate this process. For instance, TIRFM imaging has lead to a number of novel observations including imaging of constitutive exocytosis (and the surprising presence of exocytic ‘hot-spots’ for fusion on the cell surface) and nanometer targeting of microtubule plus ends to the cell surface and focal adhesions. To facilitate these and other studies multicolor TIRFM instruments, a 4D spinning disk confocal and electrophysiology instrumentation has been recently implemented here as part of “The CINEMA Lab” ("Cinema Imaging Using New Microscopy Approaches"), with support from Ludwig Institute for Cancer Research (LICR), various grants, Yale and the private sector. We are also collaborating with other groups at Yale (Dr. Jim Duncan’s group, Dept. of Biomedical Engineering) and overseas (Elena Diaz, Spain) to develop novel software to detect, analyze and make computational cellular models of these processes.
Medical Subject Headings (MeSH)
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
James Duncan, PhD
Joerg Bewersdorf, PhD
Hai Feng Zhang
Jenny Huanjiao Zhou, MD, PhD
Jiasheng Zhang, MD
Jonathan Bogan, MD
Nanotechnology
Optics and Photonics
Publications
2024
Unraveling cellular complexity with transient adapters in highly multiplexed super-resolution imaging
Schueder F, Rivera-Molina F, Su M, Marin Z, Kidd P, Rothman J, Toomre D, Bewersdorf J. Unraveling cellular complexity with transient adapters in highly multiplexed super-resolution imaging. Cell 2024, 187: 1769-1784.e18. PMID: 38552613, DOI: 10.1016/j.cell.2024.02.033.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsInter-organelle contactsSuper-resolutionMultiplexed super-resolution microscopyIntricate spatial relationshipsGolgi stacksMammalian cellsCellular functionsSuper-resolution microscopyPrimary ciliaSuper-resolution fluorescence microscopyCellular complexityTransient adaptationFluorescence microscopyDNA-PAINTFluorogenic labelingMolecular targetsSpatial relationshipsImagesThroughputMechanisms of vesicle docking and fusion pore expansion by calcium-sensor synaptotagmin-1
Cheppali S, Tsemperouli M, Chetrit D, Rivera-Molina F, Toomre D, Karatekin E. Mechanisms of vesicle docking and fusion pore expansion by calcium-sensor synaptotagmin-1. Biophysical Journal 2024, 123: 381a. DOI: 10.1016/j.bpj.2023.11.2328.Peer-Reviewed Original Research
2023
Optogenetic Control of Oncogenic Signaling in B-Cell Malignancies
Kume K, Lee J, Cheng Z, Robinson M, Leveille E, Cosgun K, Chan L, Feng Y, Arce D, Khanduja D, Toomre D, Müschen M. Optogenetic Control of Oncogenic Signaling in B-Cell Malignancies. Blood 2023, 142: 4138. DOI: 10.1182/blood-2023-190926.Peer-Reviewed Original ResearchConceptsB-cell malignanciesB-cell lymphomaMature B-cell lymphomasB cell deathB cellsB cell developmentGenetic deletionMantle cell lymphomaNF-kB signalingBCR signal inhibitorsB cell precursorsCell of originCell viabilityChronic active BCRB cell survivalB cell receptor signalsHodgkin's diseaseMultiple myelomaNormal B cell developmentPlasma cellsBtk tyrosine kinaseCell lymphomaBurkitt's lymphomaNF-kBSmall molecule inhibitors
2019
New software for automated cilia detection in cells (ACDC)
Lauring MC, Zhu T, Luo W, Wu W, Yu F, Toomre D. New software for automated cilia detection in cells (ACDC). Cilia 2019, 8: 1. PMID: 31388414, PMCID: PMC6670212, DOI: 10.1186/s13630-019-0061-z.Peer-Reviewed Original ResearchCitationsAltmetricConceptsManual analysisNew softwareData setsHighest F1 scoreTraditional manual analysisSoftware applicationsF1 scoreDetection accuracyUser biasRepresentative imagesInput dataSoftwareIntensity standard deviationEntire data setMain stepsParameter combinationsFalse positivesExperimental data setsKey metricsImagesSpeed enhancementAccuracyFalse negative rateMicroscopic imagesImage magnificationAcylation – A New Means to Control Traffic Through the Golgi
Ernst AM, Toomre D, Bogan JS. Acylation – A New Means to Control Traffic Through the Golgi. Frontiers In Cell And Developmental Biology 2019, 7: 109. PMID: 31245373, PMCID: PMC6582194, DOI: 10.3389/fcell.2019.00109.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCitationsAltmetricConceptsDiverse protein clientsSorting of proteinsIntegral membrane proteinsProtein clientsS-acylationGolgi networkProtein adaptersMembrane proteinsAnterograde fluxLipid modificationGolgi cisternaeGolgiLipid acylationNeurodegenerative diseasesHuman physiologyProteinPotential relevanceOrganellesRecent dataRapid trafficAcylationCisternaePhysiologyCargoMechanismLabeling Strategies Matter for Super-Resolution Microscopy: A Comparison between HaloTags and SNAP-tags
Erdmann RS, Baguley SW, Richens JH, Wissner RF, Xi Z, Allgeyer ES, Zhong S, Thompson AD, Lowe N, Butler R, Bewersdorf J, Rothman JE, St Johnston D, Schepartz A, Toomre D. Labeling Strategies Matter for Super-Resolution Microscopy: A Comparison between HaloTags and SNAP-tags. Cell Chemical Biology 2019, 26: 584-592.e6. PMID: 30745239, PMCID: PMC6474801, DOI: 10.1016/j.chembiol.2019.01.003.Peer-Reviewed Original ResearchCitationsAltmetric
2018
Seeing the long tail: A novel green fluorescent protein, SiriusGFP, for ultra long timelapse imaging
Zhong S, Rivera-Molina F, Rivetta A, Toomre D, Santos-Sacchi J, Navaratnam D. Seeing the long tail: A novel green fluorescent protein, SiriusGFP, for ultra long timelapse imaging. Journal Of Neuroscience Methods 2018, 313: 68-76. PMID: 30578868, PMCID: PMC9431725, DOI: 10.1016/j.jneumeth.2018.12.008.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsSuper-resolution structured illumination microscopyFluorescent proteinNovel green fluorescent proteinGreen fluorescent proteinMembrane proteinsPhotostable variantsCell biologyC-terminusStructured illumination microscopyEGFPProteinConfocal imagingSIM imagingCombination of novelIllumination microscopyKey mutationsKnown mutationsOmp25High intensity excitationMutationsLight intensityCo-operative effectSustained fluorescencePhotobleachingMisfoldingS-Palmitoylation Sorts Membrane Cargo for Anterograde Transport in the Golgi
Ernst AM, Syed SA, Zaki O, Bottanelli F, Zheng H, Hacke M, Xi Z, Rivera-Molina F, Graham M, Rebane AA, Björkholm P, Baddeley D, Toomre D, Pincet F, Rothman JE. S-Palmitoylation Sorts Membrane Cargo for Anterograde Transport in the Golgi. Developmental Cell 2018, 47: 479-493.e7. PMID: 30458139, PMCID: PMC6251505, DOI: 10.1016/j.devcel.2018.10.024.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsS-palmitoylationAnterograde cargoAnterograde signalMembrane cargoCargo selectionTransmembrane domainMembrane proteinsGolgi membranesGolgiSpecific signalsMembrane interfaceModel systemCargoProteinRate of transportAnterograde transportVesiclesCisternaeCurved regionsMembraneTransportRegionSignalsDomainFluorescenceAssessing photodamage in live-cell STED microscopy
Kilian N, Goryaynov A, Lessard MD, Hooker G, Toomre D, Rothman JE, Bewersdorf J. Assessing photodamage in live-cell STED microscopy. Nature Methods 2018, 15: 755-756. PMID: 30275592, PMCID: PMC6915835, DOI: 10.1038/s41592-018-0145-5.Peer-Reviewed Original ResearchCitationsAltmetricThe Rab-effector protein RABEP2 regulates endosomal trafficking to mediate vascular endothelial growth factor receptor-2 (VEGFR2)-dependent signaling
Kofler N, Corti F, Rivera-Molina F, Deng Y, Toomre D, Simons M. The Rab-effector protein RABEP2 regulates endosomal trafficking to mediate vascular endothelial growth factor receptor-2 (VEGFR2)-dependent signaling. Journal Of Biological Chemistry 2018, 293: 4805-4817. PMID: 29425100, PMCID: PMC5880142, DOI: 10.1074/jbc.m117.812172.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsAnimalsEndosomesEndothelial CellsMiceMice, Inbred BALB CProtein TransportProtein Tyrosine Phosphatase, Non-Receptor Type 1Rab GTP-Binding ProteinsRab4 GTP-Binding ProteinsRab7 GTP-Binding ProteinsSignal TransductionVascular Endothelial Growth Factor Receptor-2Vesicular Transport ProteinsConceptsEndosomal traffickingVascular endothelial growth factor receptor 2Phosphotyrosine phosphatase 1BVEGFR2 traffickingEndothelial growth factor receptor 2Small GTPase Rab4Rab effector proteinsEndothelial cell functionRab7-positive endosomesCell functionRab GTPaseSorting endosomesCell surface expressionMaster regulatorEndosomal compartmentsVEGFR2 degradationPhosphatase 1BRABEP2Dependent signalingVascular developmentVEGFR2 signalingHigh-resolution microscopyTraffickingEndosomesBiochemical assays
Academic Achievements and Community Involvement
honor Kavli Fellow
National AwardUS National Academy of SciencesDetails01/01/2008United Stateshonor NIH Director New Innovator Award
National AwardNIHDetails01/01/2007United States
Links & Media
News
- March 28, 2024Source: Cell
FLASH-PAINT enables highly-multiplexed super-resolution microscopy
- July 11, 2018Source: Medicine@Yale
Seeing How Cells Work as Never Before
- June 27, 2018
Seeing how cells work as never before
- May 04, 2016
Latest News from the Burd Lab
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Contacts
Cell Biology
PO Box 208002, 333 Cedar Street
New Haven, CT 06520-8002
United States