Featured Publications
Stimulation of the hepatoportal nerve plexus with focused ultrasound restores glucose homoeostasis in diabetic mice, rats and swine
Cotero V, Graf J, Miwa H, Hirschstein Z, Qanud K, Huerta TS, Tai N, Ding Y, Jimenez-Cowell K, Tomaio JN, Song W, Devarajan A, Tsaava T, Madhavan R, Wallace K, Loghin E, Morton C, Fan Y, Kao TJ, Akhtar K, Damaraju M, Barenboim L, Maietta T, Ashe J, Tracey KJ, Coleman TR, Di Carlo D, Shin D, Zanos S, Chavan SS, Herzog RI, Puleo C. Stimulation of the hepatoportal nerve plexus with focused ultrasound restores glucose homoeostasis in diabetic mice, rats and swine. Nature Biomedical Engineering 2022, 6: 683-705. PMID: 35361935, PMCID: PMC10127248, DOI: 10.1038/s41551-022-00870-w.Peer-Reviewed Original ResearchConceptsGlucose homeostasisGlucose toleranceNerve plexusAfferent autonomic nervesHyperinsulinemic euglycaemic clampNon-pharmacologic therapiesType 2 diabetesInsulin-resistant diabetesHepatic portal systemAutonomic nervesNerve pathwaysDiabetic miceFocused ultrasound stimulationPeripheral neuronsSensory projectionsIntestinal tissueMetabolic diseasesMulti-omics profilingPortal systemMetabolic tissuesGlucose availabilityDiabetesSelective activationPlexusUltrasound stimulation
2019
O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth
Singh JP, Qian K, Lee JS, Zhou J, Han X, Zhang B, Ong Q, Ni W, Jiang M, Ruan HB, Li MD, Zhang K, Ding Z, Lee P, Singh K, Wu J, Herzog RI, Kaech S, Wendel HG, Yates JR, Han W, Sherwin RS, Nie Y, Yang X. O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth. Oncogene 2019, 39: 560-573. PMID: 31501520, PMCID: PMC7107572, DOI: 10.1038/s41388-019-0975-3.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAcetylglucosamineAnimalsAntigens, NeoplasmCarrier ProteinsCell Line, TumorDatasets as TopicDisease ProgressionFemaleGene Expression ProfilingGlycolysisHEK293 CellsHistone AcetyltransferasesHumansHyaluronoglucosaminidaseMaleMembrane ProteinsMiceN-AcetylglucosaminyltransferasesNeoplasm GradingNeoplasm StagingNeoplasmsProtein Processing, Post-TranslationalThyroid HormonesTissue Array AnalysisUp-RegulationXenograft Model Antitumor AssaysConceptsPyruvate kinase M2O-GlcNAcaseAerobic glycolysisO-GlcNAcylationKinase M2Lysine acetyltransferase activityTumor growthMetabolic rheostatAcetyltransferase activityGlcNAc transferaseMolecular basisMetabolic shiftHuman cancersGlycolysisCancer cellsHigh glucose conditionsGlucose availabilityTumor progressionGlucose conditionsExquisite controlGrowthRheostatCausative roleTargetEnzymeMitochondrial MsrB2 serves as a switch and transducer for mitophagy
Lee SH, Lee S, Du J, Jain K, Ding M, Kadado AJ, Atteya G, Jaji Z, Tyagi T, Kim W, Herzog RI, Patel A, Ionescu CN, Martin KA, Hwa J. Mitochondrial MsrB2 serves as a switch and transducer for mitophagy. EMBO Molecular Medicine 2019, 11: emmm201910409. PMID: 31282614, PMCID: PMC6685081, DOI: 10.15252/emmm.201910409.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood PlateletsCell LineDiabetes MellitusFemaleHumansMethionine Sulfoxide ReductasesMice, Inbred C57BLMice, KnockoutMicrofilament ProteinsMicrotubule-Associated ProteinsMitochondriaMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition PoreMitophagyMutationOxidation-ReductionOxidative StressParkinson DiseaseSignal TransductionUbiquitinationUbiquitin-Protein LigasesConceptsReduced mitophagyOxidative stress-induced mitophagyNovel regulatory mechanismStress-induced mitophagyLC3 interactionMitochondrial matrixDamaged mitochondriaMsrB2Reactive oxygen speciesRegulatory mechanismsMethionine oxidationMitophagyMitochondriaPlatelet apoptosisOxygen speciesPlatelet-specific knockoutApoptosisPathophysiological importanceExpressionImportant roleUbiquitinationParkin mutationsParkinSpeciesLC3
2017
β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares
Goldberg EL, Asher JL, Molony RD, Shaw AC, Zeiss CJ, Wang C, Morozova-Roche LA, Herzog RI, Iwasaki A, Dixit VD. β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares. Cell Reports 2017, 18: 2077-2087. PMID: 28249154, PMCID: PMC5527297, DOI: 10.1016/j.celrep.2017.02.004.Peer-Reviewed Original ResearchConceptsKetogenic dietGouty flaresΒ-hydroxybutyrateMajor risk factorAnti-inflammatory moleculesNLRP3-dependent mannerAlternate metabolic fuelsGout flaresJoint destructionIL-1βIntense painInterleukin-1βNLRP3 inflammasomeRisk factorsInflammatory neutrophilsBacterial infectionsNeutrophilsNLRP3Immune defenseGoutMetabolic fuelsBHBS100A9 fibrilsDietPain
2016
Pigment epithelium‐derived factor restoration increases bone mass and improves bone plasticity in a model of osteogenesis imperfecta type VI via Wnt3a blockade
Belinsky GS, Sreekumar B, Andrejecsk JW, Saltzman WM, Gong J, Herzog RI, Lin S, Horsley V, Carpenter TO, Chung C. Pigment epithelium‐derived factor restoration increases bone mass and improves bone plasticity in a model of osteogenesis imperfecta type VI via Wnt3a blockade. The FASEB Journal 2016, 30: 2837-2848. PMID: 27127101, PMCID: PMC4970601, DOI: 10.1096/fj.201500027r.Peer-Reviewed Original ResearchConceptsPigment epithelium-derived factorOsteogenesis imperfecta type VIWnt/β-catenin signalingBone massOI type VIΒ-catenin signalingAbility of PEDFTrabecular bone volume/total volumeType VIBone volume/total volumeWild-type miceEpithelium-derived factorBone plasticityPEDF-knockout miceMesenchymal stem cell commitmentBone volume fractionKO micePEDF peptidesStem cell commitmentFluorescent protein reporterCombination of Wnt3aMouse modelWnt modulatorsBone mineralizationMice
2015
Hyperglycemia repression of miR-24 coordinately upregulates endothelial cell expression and secretion of von Willebrand factor
Xiang Y, Cheng J, Wang D, Hu X, Xie Y, Stitham J, Atteya G, Du J, Tang WH, Lee SH, Leslie K, Spollett G, Liu Z, Herzog E, Herzog RI, Lu J, Martin KA, Hwa J. Hyperglycemia repression of miR-24 coordinately upregulates endothelial cell expression and secretion of von Willebrand factor. Blood 2015, 125: 3377-3387. PMID: 25814526, PMCID: PMC4447857, DOI: 10.1182/blood-2015-01-620278.Peer-Reviewed Original ResearchConceptsVon Willebrand factorDiabetes mellitusMiR-24Diabetic patientsAdverse thrombotic eventsThrombotic cardiovascular eventsVWF expressionWillebrand factorDiabetic mouse modelNovel therapeutic targetHistamine H1 receptorsEndothelial cell expressionHyperglycemia-induced activationCardiovascular eventsThrombotic eventsH1 receptorsMouse modelVWF levelsTherapeutic targetCell expressionMellitusPatientsEndothelial cellsElevated levelsReactive oxygen species
2013
Vaccination with Single Chain Antigen Receptors for Islet-Derived Peptides Presented on I-Ag7 Delays Diabetes in NOD Mice by Inducing Anergy in Self-Reactive T-Cells
Gurr W, Shaw M, Herzog RI, Li Y, Sherwin R. Vaccination with Single Chain Antigen Receptors for Islet-Derived Peptides Presented on I-Ag7 Delays Diabetes in NOD Mice by Inducing Anergy in Self-Reactive T-Cells. PLOS ONE 2013, 8: e69464. PMID: 23894487, PMCID: PMC3722102, DOI: 10.1371/journal.pone.0069464.Peer-Reviewed Original ResearchConceptsSelf-reactive T cellsSingle chain receptorT cellsNOD miceB cellsReceptor repertoireSelf-reactive T cell clonesT cell receptor repertoireAnti-idiotypic vaccinationNormal NOD micePancreatic lymph nodesOnset of T1D.NOD-scid recipientsB cell receptor repertoireType 1 diabetesT cell clonesBDC2.5 TCRNOD recipientsProfound anergyLymph nodesSpecific autoantigensInducer cellsVaccination approachesMHC IVaccinationLactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia
Herzog RI, Jiang L, Herman P, Zhao C, Sanganahalli BG, Mason GF, Hyder F, Rothman DL, Sherwin RS, Behar KL. Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia. Journal Of Clinical Investigation 2013, 123: 1988-1998. PMID: 23543056, PMCID: PMC3638906, DOI: 10.1172/jci65105.Peer-Reviewed Original ResearchConceptsAntecedent recurrent hypoglycemiaRecurrent hypoglycemiaHypoglycemic conditionsIntensive insulin therapyTight glycemic controlType 2 diabetesInsulin therapyGlycemic controlBrain metabolismElevated lactateNeuronal metabolismRodent modelsNeuronal activityGlucose metabolismHypoglycemiaLactate uptakeNeuronal functionType 1Metabolic regulatorOxidative capacityModest incrementLactateMetabolismUnexpected findingBrain
2009
Recurrent Antecedent Hypoglycemia Alters Neuronal Oxidative Metabolism In Vivo
Jiang L, Herzog RI, Mason GF, de Graaf RA, Rothman DL, Sherwin RS, Behar KL. Recurrent Antecedent Hypoglycemia Alters Neuronal Oxidative Metabolism In Vivo. Diabetes 2009, 58: 1266-1274. PMID: 19276443, PMCID: PMC2682668, DOI: 10.2337/db08-1664.Peer-Reviewed Original ResearchConceptsAntecedent recurrent hypoglycemiaAcute hypoglycemiaRecurrent hypoglycemiaEuglycemic conditionsGlucose utilizationRecurrent insulin-induced hypoglycemiaWhole-brain glucose metabolismNeuronal oxidative metabolismInsulin-induced hypoglycemiaHyperinsulinemic-hypoglycemic clampAntecedent hypoglycemiaPyruvate dehydrogenase fluxHigh glucose utilizationBrain metabolismRat modelHypoglycemiaGlucose metabolismHypoglycemic conditionsBrain metabolitesBrain functionTricarboxylic acid cycle activityOxidative metabolismEnergy substratesEuglycemiaInfusion
2008
Increased GABAergic Tone in the Ventromedial Hypothalamus Contributes to Suppression of Counterregulatory Reponses After Antecedent Hypoglycemia
Chan O, Cheng H, Herzog R, Czyzyk D, Zhu W, Wang A, McCrimmon RJ, Seashore MR, Sherwin RS. Increased GABAergic Tone in the Ventromedial Hypothalamus Contributes to Suppression of Counterregulatory Reponses After Antecedent Hypoglycemia. Diabetes 2008, 57: 1363-1370. PMID: 18375441, PMCID: PMC5518793, DOI: 10.2337/db07-1559.Peer-Reviewed Original ResearchConceptsVMH GABA levelsVentromedial hypothalamusGlutamic acid decarboxylaseHypoglycemic animalsHypoglycemic ratsSympathoadrenal responseRecurrent hypoglycemiaCounterregulatory responsesGABAergic toneInhibitory toneGABA levelsHypoglycemia-associated autonomic failureGABAergic inhibitory toneOnset of hypoglycemiaGABA synthetic enzymeQuantitative RT-PCRAntecedent hypoglycemiaAutonomic failureHypoglycemic stimulusReceptor blockadeEpinephrine releaseAcute hypoglycemiaReceptor antagonistInhibitory neurotransmitterSubsequent boutEffect of Acute and Recurrent Hypoglycemia on Changes in Brain Glycogen Concentration
Herzog RI, Chan O, Yu S, Dziura J, McNay EC, Sherwin RS. Effect of Acute and Recurrent Hypoglycemia on Changes in Brain Glycogen Concentration. Endocrinology 2008, 149: 1499-1504. PMID: 18187548, PMCID: PMC2276713, DOI: 10.1210/en.2007-1252.Peer-Reviewed Original ResearchConceptsHypoglycemia-associated autonomic failureRecurrent hypoglycemiaAcute hypoglycemiaAutonomic failureBrain glycogenGlycogen levelsBrain glucoseGlucose levelsRH groupInsulin-induced acute hypoglycemiaSimilar blood glucose levelsIntensive insulin treatmentHyperinsulinemic-hypoglycemic clamp studyBrain glycogen concentrationHypoglycemic clamp studiesBlood glucose levelsBrain glucose levelsCounterregulatory failureDiabetic patientsGlycogen supercompensationRecurrent episodesSingle boutInsulin treatmentClamp studiesAnimal models
2005
Pharmacological properties of neuronal TTX-resistant sodium channels and the role of a critical serine pore residue
Leffler A, Herzog RI, Dib-Hajj SD, Waxman SG, Cummins TR. Pharmacological properties of neuronal TTX-resistant sodium channels and the role of a critical serine pore residue. Pflügers Archiv - European Journal Of Physiology 2005, 451: 454-463. PMID: 15981012, DOI: 10.1007/s00424-005-1463-x.Peer-Reviewed Original ResearchNav1.6 channels generate resurgent sodium currents in spinal sensory neurons
Cummins TR, Dib-Hajj SD, Herzog RI, Waxman SG. Nav1.6 channels generate resurgent sodium currents in spinal sensory neurons. FEBS Letters 2005, 579: 2166-2170. PMID: 15811336, DOI: 10.1016/j.febslet.2005.03.009.Peer-Reviewed Original ResearchConceptsResurgent sodium currentsResurgent currentsDRG neuronsLarge-diameter dorsal root ganglion neuronsSodium currentDorsal root ganglion neuronsSmall DRG neuronsSpinal sensory neuronsWild-type miceCerebellar Purkinje neuronsVoltage-gated sodium channelsGanglion neuronsSensory neuronsPurkinje neuronsNull miceNav1.6 channelsNeuronsSodium channelsMiceCell background
2003
Calmodulin Binds to the C Terminus of Sodium Channels Nav1.4 and Nav1.6 and Differentially Modulates Their Functional Properties
Herzog RI, Liu C, Waxman SG, Cummins TR. Calmodulin Binds to the C Terminus of Sodium Channels Nav1.4 and Nav1.6 and Differentially Modulates Their Functional Properties. Journal Of Neuroscience 2003, 23: 8261-8270. PMID: 12967988, PMCID: PMC6740705, DOI: 10.1523/jneurosci.23-23-08261.2003.Peer-Reviewed Original ResearchConceptsVoltage-gated sodium channelsSodium channelsNeuronal sodium channelsCalcium-independent mechanismVGSC isoformsNeuronal plasticityCell excitabilityNav1.6 channelsNav1.6Overexpression of CaMCalcium-dependent mannerCalcium-independent mannerNav1.4Sodium channel Nav1.4Channel Nav1.4Functional expressionCurrent amplitudeDistinct repriming and closed-state inactivation kinetics of Nav1.6 and Nav1.7 sodium channels in mouse spinal sensory neurons
Herzog RI, Cummins TR, Ghassemi F, Dib-Hajj SD, Waxman SG. Distinct repriming and closed-state inactivation kinetics of Nav1.6 and Nav1.7 sodium channels in mouse spinal sensory neurons. The Journal Of Physiology 2003, 551: 741-750. PMID: 12843211, PMCID: PMC2343279, DOI: 10.1113/jphysiol.2003.047357.Peer-Reviewed Original ResearchAnesthetics, LocalAnimalsCells, CulturedGanglia, SpinalIon Channel GatingKineticsMiceMice, Mutant StrainsNAV1.6 Voltage-Gated Sodium ChannelNAV1.7 Voltage-Gated Sodium ChannelNAV1.8 Voltage-Gated Sodium ChannelNerve Tissue ProteinsNeurons, AfferentPatch-Clamp TechniquesRecombinant ProteinsSodium ChannelsTetrodotoxinThe pentapeptide QYNAD does not block voltage-gated sodium channels
Cummins T, Renganathan M, Herzog R, Dib-Hajj S, Waxman S, Stys P, Horn R. The pentapeptide QYNAD does not block voltage-gated sodium channels. Neurology 2003, 60: 1871-1872. PMID: 12796562, DOI: 10.1212/wnl.60.11.1871-a.Peer-Reviewed Original ResearchThe pentapeptide QYNAD does not block voltage-gated sodium channels
Cummins TR, Renganathan M, Stys PK, Herzog RI, Scarfo K, Horn R, Dib-Hajj SD, Waxman SG. The pentapeptide QYNAD does not block voltage-gated sodium channels. Neurology 2003, 60: 224-229. PMID: 12552035, DOI: 10.1212/01.wnl.0000042423.36650.bd.Peer-Reviewed Original ResearchConceptsVoltage-gated sodium channelsSodium channelsDifferent sodium channel subtypesSodium currentDorsal root ganglion neuronsInflammatory neurologic disordersMajor sodium channelPatch-clamp recordingsSodium channel subtypesSodium channel functionNodes of RanvierPentapeptide QYNADOptic nerveGanglion neuronsIntact neuronsNeurologic disordersQYNADChannel subtypesHuman CSFAbnormal myelinFiber tractsElevated levelsEndogenous pentapeptideMicro MChannel function
2001
Persistent TTX-Resistant Na+ Current Affects Resting Potential and Response to Depolarization in Simulated Spinal Sensory Neurons
Herzog RI, Cummins TR, Waxman SG. Persistent TTX-Resistant Na+ Current Affects Resting Potential and Response to Depolarization in Simulated Spinal Sensory Neurons. Journal Of Neurophysiology 2001, 86: 1351-1364. PMID: 11535682, DOI: 10.1152/jn.2001.86.3.1351.Peer-Reviewed Original ResearchConceptsPersistent TTX-R currentTTX-R currentsSmall DRG neuronsSodium currentDRG neuronsSmall dorsal root ganglion neuronsTTX-resistant sodium currentsDorsal root ganglion neuronsVoltage-gated sodium currentTetrodotoxin-sensitive sodium currentTTX-S currentsSpinal sensory neuronsGanglion neuronsNeuronal excitabilitySensory neuronsAction potentialsNeuronsSubthreshold stimuliDepolarizing phaseSpike electrogenesisAnode break excitationElectrogenic propertiesBreak excitationPossible contributionInactivation gateNav1.3 Sodium Channels: Rapid Repriming and Slow Closed-State Inactivation Display Quantitative Differences after Expression in a Mammalian Cell Line and in Spinal Sensory Neurons
Cummins TR, Aglieco F, Renganathan M, Herzog RI, Dib-Hajj SD, Waxman SG. Nav1.3 Sodium Channels: Rapid Repriming and Slow Closed-State Inactivation Display Quantitative Differences after Expression in a Mammalian Cell Line and in Spinal Sensory Neurons. Journal Of Neuroscience 2001, 21: 5952-5961. PMID: 11487618, PMCID: PMC6763143, DOI: 10.1523/jneurosci.21-16-05952.2001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxotomyBiolisticsCells, CulturedGanglia, SpinalGene ExpressionGenes, ReporterHumansIon Channel GatingKidneyMaleMembrane PotentialsMutagenesis, Site-DirectedNeurons, AfferentPatch-Clamp TechniquesPolymerase Chain ReactionProtein SubunitsRatsReaction TimeSodiumSodium ChannelsSpinal CordTetrodotoxinConceptsNav1.3 channelsRapid reprimingHEK-293 cellsDRG neuronsTTX-sensitive sodium currentDorsal root ganglion neuronsNav1.3 sodium channelsSodium channelsSpinal sensory neuronsVoltage-gated sodium channelsSteady-state inactivationLarger ramp currentsHuman embryonic kidney 293 cellsPeripheral axotomyEmbryonic kidney 293 cellsGanglion neuronsSlow depolarizationSensory neuronsVoltage-dependent propertiesKidney 293 cellsSodium currentRamp currentsNav1.3NeuronsBeta2 subunit