Featured Publications
Correlative three-dimensional super-resolution and block-face electron microscopy of whole vitreously frozen cells
Hoffman DP, Shtengel G, Xu CS, Campbell KR, Freeman M, Wang L, Milkie DE, Pasolli HA, Iyer N, Bogovic JA, Stabley DR, Shirinifard A, Pang S, Peale D, Schaefer K, Pomp W, Chang CL, Lippincott-Schwartz J, Kirchhausen T, Solecki DJ, Betzig E, Hess HF. Correlative three-dimensional super-resolution and block-face electron microscopy of whole vitreously frozen cells. Science 2020, 367 PMID: 31949053, PMCID: PMC7339343, DOI: 10.1126/science.aaz5357.Peer-Reviewed Original ResearchConceptsCorrelative super-resolution fluorescenceEndoplasmic reticulum-associated proteinSuper-resolution fluorescenceChromatin domainsMammalian cellsBlock-face electron microscopyDistinct proteinsTranscriptional activityBiochemical needsSpatial compartmentalizationIntranuclear vesiclesUltrastructural variabilityFrozen cellsWhole cellsFluorescence retentionCultured neuronsProteinCellsElectron microscopyCompartmentalizationVesiclesUltrastructureAdhesionDomainFluorescenceER-to-Golgi protein delivery through an interwoven, tubular network extending from ER
Weigel AV, Chang CL, Shtengel G, Xu CS, Hoffman DP, Freeman M, Iyer N, Aaron J, Khuon S, Bogovic J, Qiu W, Hess HF, Lippincott-Schwartz J. ER-to-Golgi protein delivery through an interwoven, tubular network extending from ER. Cell 2021, 184: 2412-2429.e16. PMID: 33852913, DOI: 10.1016/j.cell.2021.03.035.Peer-Reviewed Original ResearchConceptsTubular networkEarly secretory compartmentsAccurate traffickingProtein exportDiverse proteinsProtein localizationSecretory pathwayMammalian cellsSecretory compartmentsCargo entryGolgi apparatusLipid bilayersIllumination microscopyBeam scanning electron microscopyIon beam scanning electron microscopyProtein deliveryCOPIIERDynamic 3D viewsTraffickingMicrotubulesProteinVesiclesPathwayCompartmentsESCRT-mediated membrane repair protects tumor-derived cells against T cell attack
Ritter AT, Shtengel G, Xu CS, Weigel A, Hoffman DP, Freeman M, Iyer N, Alivodej N, Ackerman D, Voskoboinik I, Trapani J, Hess HF, Mellman I. ESCRT-mediated membrane repair protects tumor-derived cells against T cell attack. Science 2022, 376: 377-382. PMID: 35446649, DOI: 10.1126/science.abl3855.Peer-Reviewed Original ResearchConceptsESCRT machineryEndosomal Sorting ComplexCancer-derived cellsESCRT proteinsTarget cellsTumor-derived cellsPlasma membranePerforin poresTransport proteinsMembrane woundsMembrane repairRelease of perforinMachineryCytosolProteinCellsCytolytic attackCytotoxic T lymphocytesESCRTTumor cellsPerforin releaseGranzymesRepairApoptosisCell attack
2020
Chloroplast Sec14-like 1 (CPSFL1) is essential for normal chloroplast development and affects carotenoid accumulation in Chlamydomonas
García-Cerdán JG, Schmid EM, Takeuchi T, McRae I, McDonald KL, Yordduangjun N, Hassan AM, Grob P, Xu CS, Hess HF, Fletcher DA, Nogales E, Niyogi KK. Chloroplast Sec14-like 1 (CPSFL1) is essential for normal chloroplast development and affects carotenoid accumulation in Chlamydomonas. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 12452-12463. PMID: 32404426, PMCID: PMC7275715, DOI: 10.1073/pnas.1916948117.Peer-Reviewed Original ResearchConceptsChloroplast developmentCarotenoid accumulationNormal chloroplast developmentBiosynthesis of carotenoidsEndosymbiotic originInsertional mutantsDomain proteinsIsoprenoid precursorsOxygenic photosynthesisChloroplast structureSuch proteinsAuxiliary proteinsCarotenoid transportPhytoene synthesisLow carotenoid contentMutantsCommitted precursorsProteinChlamydomonasEssential roleImpaired biosynthesisCarotenoid contentPhotosynthesisBiosynthesisIon beam scanning electron microscopy
2018
The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles
Coulter ME, Dorobantu CM, Lodewijk GA, Delalande F, Cianferani S, Ganesh VS, Smith RS, Lim ET, Xu CS, Pang S, Wong ET, Lidov HGW, Calicchio ML, Yang E, Gonzalez DM, Schlaeger TM, Mochida GH, Hess H, Lee WA, Lehtinen MK, Kirchhausen T, Haussler D, Jacobs FMJ, Gaudin R, Walsh CA. The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles. Cell Reports 2018, 24: 973-986.e8. PMID: 30044992, PMCID: PMC6178983, DOI: 10.1016/j.celrep.2018.06.100.Peer-Reviewed Original ResearchConceptsExtracellular vesiclesMultivesicular bodiesIntraluminal vesicle formationESCRT proteinsHedgehog secretionProgenitor maintenanceMolecular mechanistic insightsComplex proteinsCell communicationEV subtypesVesicle formationChmp1AAutosomal recessive microcephalyHuman cerebral organoidsSonic hedgehogProgenitor proliferationFunction mutationsImpairs secretionAdult functionMechanistic insightsCerebral organoidsNull micePontocerebellar hypoplasiaShhProtein
2012
Correlative 3D superresolution fluorescence and electron microscopy reveal the relationship of mitochondrial nucleoids to membranes
Kopek BG, Shtengel G, Xu CS, Clayton DA, Hess HF. Correlative 3D superresolution fluorescence and electron microscopy reveal the relationship of mitochondrial nucleoids to membranes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 6136-6141. PMID: 22474357, PMCID: PMC3341004, DOI: 10.1073/pnas.1121558109.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAnimalsDNA, MitochondrialDNA-Binding ProteinsFibroblastsHigh Mobility Group ProteinsImaging, Three-DimensionalLuminescent ProteinsMiceMicroscopy, ElectronMicroscopy, FluorescenceMicroscopy, InterferenceMitochondriaMitochondrial MembranesMitochondrial ProteinsReproducibility of ResultsConceptsMitochondrial nucleoidsSuperresolution fluorescenceIon beam ablationOptical microscopy techniquesFluorescent protein labelsCellular contextUltrastructural contextDirect imagingBiological questionsBiological processesSpecific proteinsCellular ultrastructureSuperresolution microscopyProtein labelCellular architectureFluorescence microscopyLocalization microscopyEM imagesNucleoidsMicroscopy techniquesProteinSample preparation protocolElectron microscopyVivo natureMicroscopy