2023
Anatomical Diversity of the Adult Corticospinal Tract Revealed by Single-Cell Transcriptional Profiling
Golan N, Ehrlich D, Bonanno J, O'Brien R, Murillo M, Kauer S, Ravindra N, Van Dijk D, Cafferty W. Anatomical Diversity of the Adult Corticospinal Tract Revealed by Single-Cell Transcriptional Profiling. Journal Of Neuroscience 2023, 43: 7929-7945. PMID: 37748862, PMCID: PMC10669816, DOI: 10.1523/jneurosci.0811-22.2023.Peer-Reviewed Original ResearchConceptsCorticospinal tract neuronsCorticospinal tractAdult corticospinal tractIrreversible functional deficitsCortical layer 2/3Lumbar spinal cordSpinal cord injuryLayer 5 neuronsClasses of neuronsMolecular heterogeneityAxon collateralizationTract neuronsCord injuryRetrograde labelingMotor pathwaysFemale miceFunctional deficitsLayer 2/3Primary axonsSpinal cordTerminal fieldsNeuron subtypesAdult tractTherapeutic interventionsSingle-cell RNA sequencing
2022
Prdm6 controls heart development by regulating neural crest cell differentiation and migration
Hong L, Li N, Gasque V, Mehta S, Ye L, Wu Y, Li J, Gewies A, Ruland J, Hirschi KK, Eichmann A, Hendry C, van Dijk D, Mani A. Prdm6 controls heart development by regulating neural crest cell differentiation and migration. JCI Insight 2022, 7: e156046. PMID: 35108221, PMCID: PMC8876496, DOI: 10.1172/jci.insight.156046.Peer-Reviewed Original ResearchConceptsCardiac NCCNeural crest cell fateNeural crest cell differentiationSingle-cell RNA-seq analysisRNA-seq analysisDorsal neural tubeG1-S progressionFate-mapping approachCNCC migrationSpecification genesH4K20 monomethylationCell fateTranscriptomic analysisEpigenetic modifiersHeart developmentRegulated networkTranscript levelsKey regulatorMolecular mechanismsCell differentiationNeural tubePRDM6Ductus arteriosusPotential targetDifferentiationSingle-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason L, Ko A, Montgomery R, Farhadian S, Iwasaki A, Shaw A, van Dijk D, Zhao H, Kleinstein S, Hafler D, Kaminski N, Dela Cruz C. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19. Nature Communications 2022, 13: 440. PMID: 35064122, PMCID: PMC8782894, DOI: 10.1038/s41467-021-27716-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAgedAntibodies, Monoclonal, HumanizedCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedCOVID-19COVID-19 Drug TreatmentFemaleGene Expression ProfilingGene Expression RegulationHumansImmunity, InnateMaleReceptors, Antigen, B-CellReceptors, Antigen, T-CellRNA-SeqSARS-CoV-2Single-Cell AnalysisConceptsProgressive COVID-19B cell clonesSingle-cell analysisT cellsImmune responseMulti-omics single-cell analysisCOVID-19Cell clonesAdaptive immune interactionsSevere COVID-19Dynamic immune responsesGene expressionSARS-CoV-2 virusAdaptive immune systemSomatic hypermutation frequenciesCellular effectsProtein markersEffector CD8Immune signaturesProgressive diseaseHypermutation frequencyProgressive courseClassical monocytesClonesImmune interactions
2021
A neutrophil activation signature predicts critical illness and mortality in COVID-19
Meizlish ML, Pine AB, Bishai JD, Goshua G, Nadelmann ER, Simonov M, Chang CH, Zhang H, Shallow M, Bahel P, Owusu K, Yamamoto Y, Arora T, Atri DS, Patel A, Gbyli R, Kwan J, Won CH, Dela Cruz C, Price C, Koff J, King BA, Rinder HM, Wilson FP, Hwa J, Halene S, Damsky W, van Dijk D, Lee AI, Chun HJ. A neutrophil activation signature predicts critical illness and mortality in COVID-19. Blood Advances 2021, 5: 1164-1177. PMID: 33635335, PMCID: PMC7908851, DOI: 10.1182/bloodadvances.2020003568.Peer-Reviewed Original ResearchConceptsCritical illnessHealth system databaseNeutrophil activationCOVID-19Neutrophil activation signatureSevere COVID-19Intensive care unitGranulocyte colony-stimulating factorHigh mortality rateColony-stimulating factorSystem databaseHepatocyte growth factorClinical decompensationNeutrophil countImmune hyperactivationCare unitEarly elevationLipocalin-2Interleukin-8Longitudinal cohortClinical dataMortality ratePatientsIllnessActivation signatureNeuroinvasion of SARS-CoV-2 in human and mouse brain
Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, Lu P, Weizman OE, Liu F, Dai Y, Szigeti-Buck K, Yasumoto Y, Wang G, Castaldi C, Heltke J, Ng E, Wheeler J, Alfajaro MM, Levavasseur E, Fontes B, Ravindra NG, Van Dijk D, Mane S, Gunel M, Ring A, Kazmi SAJ, Zhang K, Wilen CB, Horvath TL, Plu I, Haik S, Thomas JL, Louvi A, Farhadian SF, Huttner A, Seilhean D, Renier N, Bilguvar K, Iwasaki A. Neuroinvasion of SARS-CoV-2 in human and mouse brain. Journal Of Experimental Medicine 2021, 218: e20202135. PMID: 33433624, PMCID: PMC7808299, DOI: 10.1084/jem.20202135.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Central nervous systemSARS-CoV-2 neuroinvasionImmune cell infiltratesCOVID-19 patientsType I interferon responseMultiple organ systemsCOVID-19I interferon responseHuman brain organoidsNeuroinvasive capacityCNS infectionsCell infiltrateNeuronal infectionPathological featuresCortical neuronsRespiratory diseaseDirect infectionCerebrospinal fluidNervous systemMouse brainInterferon responseOrgan systemsHuman ACE2Infection
2020
Development and Validation of the Quick COVID-19 Severity Index: A Prognostic Tool for Early Clinical Decompensation
Haimovich AD, Ravindra NG, Stoytchev S, Young HP, Wilson FP, van Dijk D, Schulz WL, Taylor RA. Development and Validation of the Quick COVID-19 Severity Index: A Prognostic Tool for Early Clinical Decompensation. Annals Of Emergency Medicine 2020, 76: 442-453. PMID: 33012378, PMCID: PMC7373004, DOI: 10.1016/j.annemergmed.2020.07.022.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedBetacoronavirusClinical Laboratory TechniquesCoronavirus InfectionsCOVID-19COVID-19 TestingEmergency Service, HospitalFemaleHumansMaleMiddle AgedOxygen Inhalation TherapyPandemicsPneumonia, ViralRespiratory InsufficiencyRetrospective StudiesRisk AssessmentSARS-CoV-2Severity of Illness IndexYoung AdultConceptsCOVID-19 Severity IndexQuick COVID-19 severity indexQuick Sequential Organ Failure AssessmentSequential Organ Failure AssessmentOrgan Failure AssessmentHours of admissionRespiratory failureSeverity IndexScoring systemSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Bedside scoring systemOxygen requirementPneumonia severity scoresHours of hospitalizationElixhauser Comorbidity IndexEmergency department patientsSeverity Index scoreCOVID-19 patientsSyndrome coronavirus 2Coronavirus disease 2019Failure AssessmentSimple scoring systemIndependent test cohortSingle cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures
Zhao Y, Amodio M, Vander Wyk B, Gerritsen B, Kumar MM, van Dijk D, Moon K, Wang X, Malawista A, Richards MM, Cahill ME, Desai A, Sivadasan J, Venkataswamy MM, Ravi V, Fikrig E, Kumar P, Kleinstein SH, Krishnaswamy S, Montgomery RR. Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures. PLOS Neglected Tropical Diseases 2020, 14: e0008112. PMID: 32150565, PMCID: PMC7082063, DOI: 10.1371/journal.pntd.0008112.Peer-Reviewed Original ResearchConceptsZika virusCell subsetsDengue virusConcurrent dengue infectionInnate cell responsesInnate immune signaturesVirus-infected individualsDivergent clinical outcomesMosquito-borne human pathogenIntact immune responsePre-existing infectionInnate cell typesSingle-cell immune profilingPublic health importanceCell typesImmune signaturesVirus patientsWest Nile virusAcute patientsClinical outcomesImmune profilingDengue infectionImmune statusFunctional statusImmune cellsNeurohormonal Blockade and Clinical Outcomes in Patients With Heart Failure Supported by Left Ventricular Assist Devices
McCullough M, Caraballo C, Ravindra NG, Miller PE, Mezzacappa C, Levin A, Gruen J, Rodwin B, Reinhardt S, van Dijk D, Ali A, Ahmad T, Desai NR. Neurohormonal Blockade and Clinical Outcomes in Patients With Heart Failure Supported by Left Ventricular Assist Devices. JAMA Cardiology 2020, 5: 175-182. PMID: 31738366, PMCID: PMC6865330, DOI: 10.1001/jamacardio.2019.4965.Peer-Reviewed Original ResearchConceptsKansas City Cardiomyopathy Questionnaire scoreNeurohormonal blockadeAngiotensin receptor blockersVentricular assist deviceQuality of lifeMineralocorticoid antagonistsReceptor blockersHeart failureWalk testQuestionnaire scoresΒ-blockersEnzyme inhibitorsAssist deviceGuideline-directed medical therapyAngiotensin-converting enzyme inhibitorMechanically Assisted Circulatory SupportHeart failure regimenLeft ventricular assist deviceAdvanced heart failureRetrospective cohort analysisContinuous-flow LVADBetter survival rateOutcomes of interestInteragency RegistryTriple therapyUncovering axes of variation among single-cell cancer specimens
Chen WS, Zivanovic N, van Dijk D, Wolf G, Bodenmiller B, Krishnaswamy S. Uncovering axes of variation among single-cell cancer specimens. Nature Methods 2020, 17: 302-310. PMID: 31932777, PMCID: PMC7339867, DOI: 10.1038/s41592-019-0689-z.Peer-Reviewed Original ResearchAlgorithmsAnimalsAntineoplastic AgentsBiopsyBreast NeoplasmsCluster AnalysisCytophotometryDrug Screening Assays, AntitumorEnzyme InhibitorsEpithelial-Mesenchymal TransitionFemaleHumansImage Interpretation, Computer-AssistedMammary Neoplasms, AnimalMiceNeoplasm MetastasisPattern Recognition, AutomatedPhenotypeRecombinant ProteinsSingle-Cell AnalysisSoftwareTransforming Growth Factor beta