Featured Publications
Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditis
Barmada A, Klein J, Ramaswamy A, Brodsky N, Jaycox J, Sheikha H, Jones K, Habet V, Campbell M, Sumida T, Kontorovich A, Bogunovic D, Oliveira C, Steele J, Hall E, Pena-Hernandez M, Monteiro V, Lucas C, Ring A, Omer S, Iwasaki A, Yildirim I, Lucas C. Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditis. Science Immunology 2023, 8: eadh3455-eadh3455. PMID: 37146127, PMCID: PMC10468758, DOI: 10.1126/sciimmunol.adh3455.Peer-Reviewed Original ResearchConceptsMRNA vaccinesSARS-CoV-2 mRNA vaccinesSARS-CoV-2 mRNA vaccinationC-reactive protein levelsB-type natriuretic peptidePeripheral blood mononuclear cellsCardiac tissue inflammationDeep immune profilingSerum soluble CD163Vaccine-associated myocarditisCohort of patientsBlood mononuclear cellsCytotoxic T cellsLate gadolinium enhancementHypersensitivity myocarditisElevated troponinMRNA vaccinationImaging abnormalitiesNK cellsImmune profilingKiller cellsMyeloid responseNatriuretic peptideHumoral mechanismsInflammatory cytokinesPlatelet-derived TLT-1 promotes tumor progression by suppressing CD8+ T cells
Tyagi T, Jain K, Yarovinsky TO, Chiorazzi M, Du J, Castro C, Griffin J, Korde A, Martin KA, Takyar SS, Flavell RA, Patel AA, Hwa J. Platelet-derived TLT-1 promotes tumor progression by suppressing CD8+ T cells. Journal Of Experimental Medicine 2022, 220: e20212218. PMID: 36305874, PMCID: PMC9814191, DOI: 10.1084/jem.20212218.Peer-Reviewed Original ResearchConceptsCD8 T cellsT cellsTLT-1Non-small cell lung cancer patientsCell lung cancer patientsTREM-like transcript-1Tumor immunosuppressive mechanismsT cell suppressionLung cancer patientsPatient T cellsNF-κB pathwayPatient-derived tumorsDistinct activation phenotypesNSCLC patientsImmunosuppressive mechanismsSyngeneic tumorsHumanized miceImmunoregulatory rolePrognostic significanceImmunocompetent miceCancer patientsCell suppressionActivation phenotypeReduced tumorTumor growthSequelae of Eating Disorders at Imaging
Solomon N, Sailer A, Dixe de Oliveira Santo I, Pillai A, Heng LXX, Jha P, Katz DS, Zulfiqar M, Sugi M, Revzin MV. Sequelae of Eating Disorders at Imaging. Radio Graphics 2022, 42: 1377-1397. PMID: 35930473, DOI: 10.1148/rg.220018.Peer-Reviewed Educational MaterialsConceptsMedical historyPatient's medical historyHigh mortality rateOverview of managementClinical presentationMedical complicationsRelated complicationsImaging findingsPhysical examinationUncommon sequelaMedical attentionOnline supplemental materialPsychiatric disordersMedical treatmentMortality rateOrgan systemsSequelaeDisordersDiagnosisComplicationsPatientsPathophysiologySocial stigmaLaboratory resultsRadiologistsA guide to molecular and functional investigations of platelets to bridge basic and clinical sciences
Tyagi T, Jain K, Gu S, Qiu M, Gu V, Melchinger H, Rinder H, Martin K, Gardiner E, Lee A, Tang W, Hwa J. A guide to molecular and functional investigations of platelets to bridge basic and clinical sciences. Nature Cardiovascular Research 2022, 1: 223-237. PMID: 37502132, PMCID: PMC10373053, DOI: 10.1038/s44161-022-00021-z.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsVascular smooth muscle cellsPlatelet functional assaysCoronavirus disease 2019Smooth muscle cellsImmune cellsImmune regulationVascular remodelingDisease 2019Pathophysiological processesTranslational relevancePatient diagnosisFlow cytometryMuscle cellsPlatelet biologyFunctional assaysPlatelet investigationsHomeostatic processesPlateletsPhenotypic heterogeneityFunctional stateClinical scienceCellsAdditional roleThrombosisSuch diverse functionsBi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions
Levey DF, Stein MB, Wendt FR, Pathak GA, Zhou H, Aslan M, Quaden R, Harrington KM, Nuñez YZ, Overstreet C, Radhakrishnan K, Sanacora G, McIntosh AM, Shi J, Shringarpure SS, Concato J, Polimanti R, Gelernter J. Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions. Nature Neuroscience 2021, 24: 954-963. PMID: 34045744, PMCID: PMC8404304, DOI: 10.1038/s41593-021-00860-2.Peer-Reviewed Original ResearchConceptsTranscriptome-wide association studyMillion Veteran ProgramTranscriptome-wide association study (TWAS) analysisGenomic risk lociComplex psychiatric traitsGenetic architectureRisk lociGene expressionAssociation studiesLikely pathogenicityPsychiatric traitsVeteran ProgramNew therapeutic directionEuropean ancestryNew insightsAncestryUK BiobankAfrican ancestrySubstantial replicationExpressionLarge independent cohortsGWASTherapeutic directionsGenesLociImmune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children
Ramaswamy A, Brodsky NN, Sumida TS, Comi M, Asashima H, Hoehn KB, Li N, Liu Y, Shah A, Ravindra NG, Bishai J, Khan A, Lau W, Sellers B, Bansal N, Guerrerio P, Unterman A, Habet V, Rice AJ, Catanzaro J, Chandnani H, Lopez M, Kaminski N, Dela Cruz CS, Tsang JS, Wang Z, Yan X, Kleinstein SH, van Dijk D, Pierce RW, Hafler DA, Lucas CL. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children. Immunity 2021, 54: 1083-1095.e7. PMID: 33891889, PMCID: PMC8043654, DOI: 10.1016/j.immuni.2021.04.003.Peer-Reviewed Original ResearchConceptsMIS-C patientsDisease severityInflammatory syndromeTCR repertoireSARS-CoV-2-associated multisystem inflammatory syndromeAsymptomatic SARS-CoV-2 infectionSARS-CoV-2 infectionAdult COVID-19Post-infectious complicationsMultisystem inflammatory syndromeCytotoxicity genesHealthy pediatricImmune dysregulationMemory TActive infectionMyeloid dysfunctionPatientsSingle-cell RNA sequencingFlow cytometrySerum proteomicsRepertoire analysisElevated expressionSeverityAlarminsCOVID-19Lesions to the mediodorsal thalamus, but not orbitofrontal cortex, enhance volatility beliefs linked to paranoia
Suthaharan P, Thompson S, Rossi-Goldthorpe R, Rudebeck P, Walton M, Chakraborty S, Noonan M, Costa V, Murray E, Mathys C, Groman S, Mitchell A, Taylor J, Corlett P, Chang S. Lesions to the mediodorsal thalamus, but not orbitofrontal cortex, enhance volatility beliefs linked to paranoia. Cell Reports 2024, 43: 114355. PMID: 38870010, PMCID: PMC11231991, DOI: 10.1016/j.celrep.2024.114355.Peer-Reviewed Original ResearchOrbitofrontal cortexMediodorsal thalamusReward learning rateAssociated with paranoiaExcitotoxic lesionsBrain regionsUnoperated monkeysAction selectionAdaptive behaviorParanoiaBelief updatingMDmcMeaningful changeCortexThalamusBeliefsLearning rateRobust to variabilityCompare performanceRewardBehaviorBrainMonkeysAction policiesPerceptionAlcohol Use Disorder and Chronic Pain: An Overlooked Epidemic
De Aquino J, Sloan M, Nunes J, Costa G, Katz J, de Oliveira D, Ra J, Tang V, Petrakis I. Alcohol Use Disorder and Chronic Pain: An Overlooked Epidemic. American Journal Of Psychiatry 2024, 181: 391-402. PMID: 38706339, DOI: 10.1176/appi.ajp.20230886.Peer-Reviewed Original ResearchConceptsAlcohol use disorderChronic painAUD studiesChronic pain disordersChronic pain outcomesRisk of relapseAlcohol withdrawal syndromeAssessment of painHigher levels of alcohol consumptionLevels of alcohol consumptionWithdrawal syndromePain disordersPain outcomesAcute toleranceNeurobiological changesClinical significanceUse disorderPainClinical relevanceSelf-reportAlcohol intoxicationAlcohol consumptionGeneral populationMedical conditionsNarrative reviewFrom taboo to treatment: The emergence of psychedelics in the management of pain and opioid use disorder
Weleff J, Nunes J, Costa G, Sofuoglu M, MacLean R, De Aquino J. From taboo to treatment: The emergence of psychedelics in the management of pain and opioid use disorder. British Journal Of Clinical Pharmacology 2024 PMID: 38627909, DOI: 10.1111/bcp.16045.Peer-Reviewed Original ResearchOpioid use disorderChronic painLong-term opioid therapyManagement of chronic painPain management alternativeOpioid-induced analgesiaInnovative treatment optionsManagement of painReverse painCentral sensitizationOpioid therapyPain controlTreatment optionsClinical challengeClinical trialsPainPotential therapeutic applicationsPain experiencePotential of psychedelicsNovel therapeuticsHuman evidenceOpioid crisisNeurobiological substratesOpioidExploration of novel therapeuticsCOPII with ALG2 and ESCRTs control lysosome-dependent microautophagy of ER exit sites
Liao Y, Pang S, Li W, Shtengel G, Choi H, Schaefer K, Xu C, Lippincott-Schwartz J. COPII with ALG2 and ESCRTs control lysosome-dependent microautophagy of ER exit sites. Developmental Cell 2024, 59: 1410-1424.e4. PMID: 38593803, DOI: 10.1016/j.devcel.2024.03.027.Peer-Reviewed Original ResearchEndoplasmic reticulum exit sitesER exit sitesAmino acid starvationPurified recombinant componentsExit siteProtein sortingSecretory pathwayMammalian cellsNutrient stressCellular conditionsEndoplasmic reticulumGiant unilamellar vesiclesTubular outgrowthsESCRTMicroautophagyNutrient stressorsALG2COPIILysosomesPathwayMTOR inhibitionUnilamellar vesiclesRecombinant componentsFocused ion beam scanning electron microscopyIon beam scanning electron microscopyAssessing pain in persons with opioid use disorder: Approaches, techniques and special considerations
Nunes J, Costa G, Weleff J, Rogan M, Compton P, De Aquino J. Assessing pain in persons with opioid use disorder: Approaches, techniques and special considerations. British Journal Of Clinical Pharmacology 2024 PMID: 38556851, DOI: 10.1111/bcp.16055.Peer-Reviewed Original ResearchOpioid use disorderAssess painPain assessmentPain experienceConcomitant chronic painChronic opioid therapyQuantitative sensory testingVisual analogue scalePain assessment methodsPain assessment toolsComplex psychosocial backgroundImprove pain assessmentOpioid therapyOpioid usePain responseChronic painAnalogue scaleTraditional self-report methodsPainRisk factorsUse disorderOpioidNarrative reviewSelf-report methodsMultidisciplinary teamThe role of neurosteroids in posttraumatic stress disorder and alcohol use disorder: A review of 10 years of clinical literature and treatment implications
Peltier M, Verplaetse T, Altemus M, Zakiniaeiz Y, Ralevski E, Mineur Y, Gueorguieva R, Picciotto M, Cosgrove K, Petrakis I, McKee S. The role of neurosteroids in posttraumatic stress disorder and alcohol use disorder: A review of 10 years of clinical literature and treatment implications. Frontiers In Neuroendocrinology 2024, 73: 101119. PMID: 38184208, PMCID: PMC11185997, DOI: 10.1016/j.yfrne.2023.101119.Peer-Reviewed Original ResearchPosttraumatic stress disorderAlcohol use disorderStress disorderContext of PTSDPTSD/AUDConcurrent posttraumatic stress disorderUnderlying neurobiological mechanismsUse disordersAlcohol-related variablesNeurobiological mechanismsPTSD diagnosisTreatment developmentTreatment implicationsBody of literatureNovel interventionsClinical literatureRole of neurosteroidsDisordersTreatment outcomesYears of researchAlcohol consumptionExogenous pregnenolonePharmacological treatmentBiological variablesAllopregnanoloneNav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis
Fu W, Vasylyev D, Bi Y, Zhang M, Sun G, Khleborodova A, Huang G, Zhao L, Zhou R, Li Y, Liu S, Cai X, He W, Cui M, Zhao X, Hettinghouse A, Good J, Kim E, Strauss E, Leucht P, Schwarzkopf R, Guo E, Samuels J, Hu W, Attur M, Waxman S, Liu C. Nav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis. Nature 2024, 625: 557-565. PMID: 38172636, PMCID: PMC10794151, DOI: 10.1038/s41586-023-06888-7.Peer-Reviewed Original ResearchVoltage-gated sodium channelsOA progressionDorsal root ganglion neuronsStructural joint damagePain relief treatmentHuman OA chondrocytesCommon joint diseaseMultiple mouse modelsNav1.7 blockersPain behaviorGanglion neuronsPharmacological blockadeJoint damageJoint degenerationChannel blockersJoint diseaseOA chondrocytesMouse modelTherapeutic targetOsteoarthritisIntracellular Ca2Nav1.7Nav1.7 channelsGenetic ablationLimited evidenceThe impact of cannabis on non-medical opioid use among individuals receiving pharmacotherapies for opioid use disorder: a systematic review and meta-analysis of longitudinal studies
Costa G, Nunes J, Heringer D, Anand A, De Aquino J. The impact of cannabis on non-medical opioid use among individuals receiving pharmacotherapies for opioid use disorder: a systematic review and meta-analysis of longitudinal studies. The American Journal Of Drug And Alcohol Abuse 2024, 50: 12-26. PMID: 38225727, DOI: 10.1080/00952990.2023.2287406.Peer-Reviewed Original ResearchConceptsNon-medical opioid useOpioid use disorderOpioid useCannabis useOpioid use disorder pharmacotherapyUse disorderImpact of cannabis useAverage follow-up timeFollow-up timeMeta-analysisEvidence of moderate heterogeneityImpact of cannabisPooled odds ratioOpioids non-medicallyRandom-effects modelMeta-analysis of longitudinal studiesCannabis abstinenceTreatment modalitiesOdds ratioModerate heterogeneityPharmacotherapyCannabisOpioidComprehensive searchPublication biasCommon Pathways of Epileptogenesis in Patients With Epilepsy Post–Brain Injury
Misra S, Khan E, Lam T, Mazumder R, Gururangan K, Hickman L, Goswami V, Funaro M, Eldem E, Sansing L, Sico J, Quinn T, Liebeskind D, Montaner J, Kwan P, Mishra N. Common Pathways of Epileptogenesis in Patients With Epilepsy Post–Brain Injury. Neurology 2023, 101: e2243-e2256. PMID: 37550071, PMCID: PMC10727219, DOI: 10.1212/wnl.0000000000207749.Peer-Reviewed Original ResearchConceptsStandardized mean differencePoststroke epilepsyBrain injuryGenetic susceptibilityDisparate time pointsRisk of epileptogenesisLate-onset seizuresDevelopment of epilepsyBlood glucose levelsTraumatic brain injuryMean biomarker levelsIndividual genetic susceptibilityWeb of ScienceReported biomarkersPrimary outcomeEpileptogenic processBiofluid biomarkersBias assessmentBiomarker levelsCommon biological pathwaysEnrichment analysisGlucose levelsHigh riskPrognostic studiesEpilepsyMulti-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications
Levey D, Galimberti M, Deak J, Wendt F, Bhattacharya A, Koller D, Harrington K, Quaden R, Johnson E, Gupta P, Biradar M, Lam M, Cooke M, Rajagopal V, Empke S, Zhou H, Nunez Y, Kranzler H, Edenberg H, Agrawal A, Smoller J, Lencz T, Hougaard D, Børglum A, Demontis D, Gaziano J, Gandal M, Polimanti R, Stein M, Gelernter J. Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications. Nature Genetics 2023, 55: 2094-2103. PMID: 37985822, PMCID: PMC10703690, DOI: 10.1038/s41588-023-01563-z.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphism-based heritabilityMulti-ancestry genome-wide association studyAssociation studiesMillion Veteran ProgramGenome-wide association studiesWide significant lociWide association studySignificant lociReference panelSmall populationDisease biologyAncestryAmerican ancestryHeritabilityVeteran ProgramNumerous medical comorbiditiesLung cancer riskRelationship analysisLociBiologyPublic health implicationsEast AsiansPublic health consequencesMedical comorbiditiesCigarette smokingClinical characteristics and outcomes of patients with post-stroke epilepsy: protocol for an individual patient data meta-analysis from the International Post-stroke Epilepsy Research Repository (IPSERR)
Mishra N, Kwan P, Tanaka T, Sunnerhagen K, Dawson J, Zhao Y, Misra S, Wang S, Sharma V, Mazumder R, Funaro M, Ihara M, Nicolo J, Liebeskind D, Yasuda C, Cendes F, Quinn T, Ge Z, Scalzo F, Zelano J, Kasner S, Consortium I, Mishra N, Kwan P, Friedman A, Engel J. Clinical characteristics and outcomes of patients with post-stroke epilepsy: protocol for an individual patient data meta-analysis from the International Post-stroke Epilepsy Research Repository (IPSERR). BMJ Open 2023, 13: e078684. PMID: 37968000, PMCID: PMC10660442, DOI: 10.1136/bmjopen-2023-078684.Peer-Reviewed Original ResearchConceptsPost-stroke epilepsyPost-stroke seizuresIndividual patient dataClinical characteristicsLate post-stroke seizuresPatient dataOutcomes of patientsFuture clinical trialsPatient outcome measuresComprehensive search strategyAcute strokePeer-reviewed journalsStroke patientsPrognostic valueStroke mortalityBias assessmentClinical trialsObservational studyOutcome measuresLanguage of publicationEpileptic seizuresPatientsEthics approvalStudy authorsIPD-MAOutcomes in Patients With Poststroke Seizures
Misra S, Kasner S, Dawson J, Tanaka T, Zhao Y, Zaveri H, Eldem E, Vazquez J, Silva L, Mohidat S, Hickman L, Khan E, Funaro M, Nicolo J, Mazumder R, Yasuda C, Sunnerhagen K, Ihara M, Ross J, Liebeskind D, Kwan P, Quinn T, Engel J, Mishra N. Outcomes in Patients With Poststroke Seizures. JAMA Neurology 2023, 80: 1155-1165. PMID: 37721736, PMCID: PMC10507596, DOI: 10.1001/jamaneurol.2023.3240.Peer-Reviewed Original ResearchConceptsPoststroke seizuresPoor functional outcomeLate seizuresEarly seizuresStroke subtypesFunctional outcomeOdds ratioSystematic reviewJoanna Briggs Institute toolsHemorrhagic stroke subtypesOutcomes of patientsHistory of strokeTrials of interventionsRisk of biasMeta-Analyses (PRISMA) checklistPreferred Reporting ItemsMeta-regression analysisWeb of ScienceRecurrent strokeGreater disabilityPoor outcomeDementia riskSubgroup analysisBias assessmentEgger's testSequencing Quadruple Therapy for Heart Failure with Reduced Ejection Fraction: Does It Really Matter?
Hu J, Schwann A, Tan J, Nuqali A, Riello R, Beasley M. Sequencing Quadruple Therapy for Heart Failure with Reduced Ejection Fraction: Does It Really Matter? Cardiology Clinics 2023, 41: 511-524. PMID: 37743074, DOI: 10.1016/j.ccl.2023.06.007.Peer-Reviewed Original ResearchConceptsReduced ejection fractionEjection fractionHeart failureChronic kidney diseaseQuadruple therapyTarget dosingTherapy initiationAtrial fibrillationKidney diseaseSpecial populationsMedicationsConventional sequencesTolerabilityBradycardiaPatientsFailureFibrillationDosingTherapyInitiationDiseaseDosesGDMTEffectiveness of Nirmatrelvir-Ritonavir Against the Development of Post-COVID-19 Conditions Among U.S. Veterans : A Target Trial Emulation.
Ioannou G, Berry K, Rajeevan N, Li Y, Mutalik P, Yan L, Bui D, Cunningham F, Hynes D, Rowneki M, Bohnert A, Boyko E, Iwashyna T, Maciejewski M, Osborne T, Viglianti E, Aslan M, Huang G, Bajema K. Effectiveness of Nirmatrelvir-Ritonavir Against the Development of Post-COVID-19 Conditions Among U.S. Veterans : A Target Trial Emulation. Annals Of Internal Medicine 2023, 176: 1486-1497. PMID: 37903369, PMCID: PMC10620954, DOI: 10.7326/m23-1394.Peer-Reviewed Original ResearchConceptsAcute COVID-19Veterans Health AdministrationUntreated comparatorsThromboembolic eventsCOVID-19Severe COVID-19Target trial emulationSARS-CoV-2Post COVID-19 conditionIndex dateVenous thromboembolismBaseline characteristicsCumulative incidencePulmonary embolismAcute infectionMedian ageOral antiviralsTrial emulationVHA careOutpatient treatmentInternational ClassificationHealth AdministrationU.S. veteransVeterans AffairsOrgan systems