Holly Nicole Blackburn, MD
Hospital ResidentAbout
Research
Publications
2024
Mechanistic Investigation of Human DPP9 Deficiency
Xiao T, Brewer J, Zhou L, Han A, Takabe Y, Carlino M, Blackburn H, Flavell R. Mechanistic Investigation of Human DPP9 Deficiency. Blood 2024, 144: 5699-5699. DOI: 10.1182/blood-2024-211123.Peer-Reviewed Original ResearchHuman HSPCsDevelopment of human immune systemHuman NLRP1Loss of hematopoietic cellsHumanized mouse modelHuman hematopoietic stemStem cells in vivoSensors of infectionLaboratory mouse strainsCells in vivoHuman immune systemMouse genomeHematopoietic stemHuman hematopoiesisHematopoietic cellsCellular stressNegative regulatorPancytopeniaProgenitor cellsMouse strainsRegulatory pathwaysMouse modelHSPCsImmune systemDeletion
2023
1025 Tumor-specific CD8+ T cells epigenetically licensed by IL-7R are critical for anti-tumor immunity in melanoma
Micevic G, Daniels A, Flem-Karlsen K, Park K, Talty R, McGeary M, Mirza H, Blackburn H, Sefik E, Cheung J, Hornick N, Aizenbud L, Joshi N, Kluger H, Iwasaki A, Bosenberg M, Flavell R. 1025 Tumor-specific CD8+ T cells epigenetically licensed by IL-7R are critical for anti-tumor immunity in melanoma. 2023, a1133-a1133. DOI: 10.1136/jitc-2023-sitc2023.1025.Peer-Reviewed Original ResearchIL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory
Micevic G, Daniels A, Flem-Karlsen K, Park K, Talty R, McGeary M, Mirza H, Blackburn H, Sefik E, Cheung J, Hornick N, Aizenbud L, Joshi N, Kluger H, Iwasaki A, Bosenberg M, Flavell R. IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2304319120. PMID: 37459511, PMCID: PMC10372654, DOI: 10.1073/pnas.2304319120.Peer-Reviewed Original ResearchConceptsIL-7R expressionT cellsIL-7RAntitumor memorySuperior antitumor efficacyCell-based therapiesTumor-specific T cellsAntigen-specific T cellsAntitumor efficacyPowerful antitumor immune responseMarkers of exhaustionTumor-specific CD8Antitumor immune responseIndependent prognostic factorAntitumor immune memoryMemory T cellsMajor risk factorSuperior antitumor activityFunctional CD8Memory CD8Prognostic factorsSurgical resectionAdvanced melanomaLymph nodesNaive miceCutting Edge: IL-21 and Tissue-Specific Signals Instruct Tbet+CD11c+ B Cell Development following Viral Infection.
Song W, Sanchez G, Mayer D, Blackburn H, Chernova I, Flavell R, Weinstein J, Craft J. Cutting Edge: IL-21 and Tissue-Specific Signals Instruct Tbet+CD11c+ B Cell Development following Viral Infection. The Journal Of Immunology 2023, 210: 1861-1865. PMID: 37133336, PMCID: PMC10247523, DOI: 10.4049/jimmunol.2300027.Peer-Reviewed Original ResearchConceptsAge-associated B cellsIL-21Acute lymphocytic choriomeningitis virus infectionB cellsLymphocytic choriomeningitis virus infectionB cell activationHumoral immunityLymphoid organsVirus infectionMouse modelViral infectionB cell developmentCell activationLymphotoxin αVivo generationTissue-specific signalsInfectionDe novo generationOrgan contributionIFNTissue microenvironmentCell developmentLiverPivotal contributorStage-specific roles
2022
Inflammasome activation in infected macrophages drives COVID-19 pathology
Sefik E, Qu R, Junqueira C, Kaffe E, Mirza H, Zhao J, Brewer JR, Han A, Steach HR, Israelow B, Blackburn HN, Velazquez SE, Chen YG, Halene S, Iwasaki A, Meffre E, Nussenzweig M, Lieberman J, Wilen CB, Kluger Y, Flavell RA. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature 2022, 606: 585-593. PMID: 35483404, PMCID: PMC9288243, DOI: 10.1038/s41586-022-04802-1.Peer-Reviewed Original ResearchConceptsInflammasome activationLung inflammationInflammatory responseInfected macrophagesSARS-CoV-2 infectionHuman macrophagesChronic lung pathologyPersistent lung inflammationSevere COVID-19Immune inflammatory responseInflammatory cytokine productionHumanized mouse modelNLRP3 inflammasome pathwayCOVID-19 pathologyCOVID-19SARS-CoV-2Productive viral cycleHyperinflammatory stateChronic stageIL-18Cytokine productionInflammatory cytokinesLung pathologyInflammasome pathwayInterleukin-1
2021
Analysis of Survival Among Adults With Early-Onset Colorectal Cancer in the National Cancer Database
Cheng E, Blackburn HN, Ng K, Spiegelman D, Irwin ML, Ma X, Gross CP, Tabung FK, Giovannucci EL, Kunz PL, Llor X, Billingsley K, Meyerhardt JA, Ahuja N, Fuchs CS. Analysis of Survival Among Adults With Early-Onset Colorectal Cancer in the National Cancer Database. JAMA Network Open 2021, 4: e2112539. PMID: 34132794, PMCID: PMC8209612, DOI: 10.1001/jamanetworkopen.2021.12539.Peer-Reviewed Original ResearchConceptsEarly-onset colorectal cancerOnset colorectal cancerNational Cancer DatabaseColorectal cancerAge 51Overall survivalCancer DatabaseIncidence of CRCCox proportional hazards regressionPrimary colorectal cancerKaplan-Meier analysisProportional hazards regressionAge 50 yearsAge 25 yearsAnalysis of survivalCohort studySurvival benefitHazards regressionUnadjusted analysesCancer incidenceMAIN OUTCOMEAge 35Survival advantageLower riskStage IDickkopf-2 regulates the stem cell marker LGR5 in colorectal cancer via HNF4α1
Shin JH, Jeong J, Choi J, Lim J, Dinesh RK, Braverman J, Hong JY, Maher SE, Vesely M, Kim W, Koo JH, Tang W, Wu D, Blackburn HN, Xicola RM, Llor X, Yilmaz O, Choi JM, Bothwell ALM. Dickkopf-2 regulates the stem cell marker LGR5 in colorectal cancer via HNF4α1. IScience 2021, 24: 102411. PMID: 33997693, PMCID: PMC8099562, DOI: 10.1016/j.isci.2021.102411.Peer-Reviewed Original ResearchColorectal cancerDickkopf-2Colitis-associated cancerColorectal cancer stemnessStem cell marker Lgr5Colonic epithelial cellsAggressive progressionCancer stemnessLGR5 expressionColonic organoidsCancerEpithelial cellsCell marker genesStem cell marker genesSignificant increaseGenetic depletionWnt ligandsStem cellsProgressionLgr5StemnessCellsExpressionSequential mutationsMutations
2020
Paracrine orchestration of intestinal tumorigenesis by a mesenchymal niche
Roulis M, Kaklamanos A, Schernthanner M, Bielecki P, Zhao J, Kaffe E, Frommelt LS, Qu R, Knapp MS, Henriques A, Chalkidi N, Koliaraki V, Jiao J, Brewer JR, Bacher M, Blackburn HN, Zhao X, Breyer RM, Aidinis V, Jain D, Su B, Herschman HR, Kluger Y, Kollias G, Flavell RA. Paracrine orchestration of intestinal tumorigenesis by a mesenchymal niche. Nature 2020, 580: 524-529. PMID: 32322056, PMCID: PMC7490650, DOI: 10.1038/s41586-020-2166-3.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, LyArachidonic AcidCarcinogenesisCell Cycle ProteinsCell ProliferationColorectal NeoplasmsCyclooxygenase 2DinoprostoneFemaleFibroblastsHumansIntestinal MucosaIntestinesMaleMembrane ProteinsMesodermMiceNeoplastic Stem CellsOrganoidsParacrine CommunicationReceptors, Prostaglandin E, EP4 SubtypeSingle-Cell AnalysisStem Cell NicheYAP-Signaling ProteinsConceptsSingle-cell RNA-sequencing analysisTumor-initiating stem cellsRNA sequence analysisMesenchymal nicheStem cellsTumor initiationSca-1Hippo pathway effector YAPStem cell functionCell expansionPathway effector YAPMutant stem cellsEpithelial-specific ablationIntestinal stem cellsEarly tumor initiationProstaglandin E2Regenerative reprogrammingNormal epithelial stem cellsParacrine controlTumorigenic programsNiche modelsNuclear localizationTranscriptional activityYAP dephosphorylationEpithelial stem cells
2018
Identifying the low risk patient in surgical intensive and intermediate care units using continuous monitoring
Blackburn HN, Clark MT, Moorman JR, Lake DE, Calland JF. Identifying the low risk patient in surgical intensive and intermediate care units using continuous monitoring. Surgery 2018, 163: 811-818. PMID: 29433853, DOI: 10.1016/j.surg.2017.08.022.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overCritical CareCritical IllnessDecision Support TechniquesFemaleHumansIntensive Care UnitsMaleMiddle AgedMonitoring, PhysiologicPatient DischargePatient ReadmissionPoint-of-Care SystemsPredictive Value of TestsRetrospective StudiesRisk AssessmentYoung AdultConceptsIntermediate care unitIntensive care unitSafe patient dischargeCare unitFavorable outcomeNegative predictive valueAdverse eventsCritical illnessPatient dischargePredictive valueSurgical intensive care unitLow-risk patientsAdmitting servicesHospital durationRisk patientsAdverse outcomesWorse outcomesRelative riskPatientsSignificant predictorsOutcomesCharacteristic curveIllnessLowest decileRisk
2016
External validation in an intermediate unit of a respiratory decompensation model trained in an intensive care unit
Blackburn HN, Clark MT, Moss TJ, Young JS, Moorman JR, Lake DE, Calland JF. External validation in an intermediate unit of a respiratory decompensation model trained in an intensive care unit. Surgery 2016, 161: 760-770. PMID: 27894709, DOI: 10.1016/j.surg.2016.09.018.Peer-Reviewed Original ResearchConceptsIntensive care unitCare unitIntermediate care patientsLevel of careRelative riskUrgent intubationCare patientsSurgical intermediate care unitIntermediate care unitDuration of stayLowest decileObserved relative riskAdverse eventsSubclinical deteriorationHeart ratePatientsIntubationVital signsEarly detectionDemonstrated areasExternal validationRiskCareSeparate populationsHours