Edward Doherty, PhD
Associate Research Scientist (Rheumatology, Allergy & Immunology)Cards
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Associate Research Scientist (Rheumatology, Allergy & Immunology)
Biography
Dr. Edward Doherty studies the immune system and the dysregulation of the immune response that leads to autoimmunity. He focuses on the role of MIF receptor expressing T cells he identified in health and disease.
Appointments
Rheumatology
Associate Research ScientistPrimary
Other Departments & Organizations
Education & Training
- PhD
- State University of New York Upstate, Immunology
- BS
- University of New England, Biology
Research
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Overview
MIF is the first cytokine activity to be described and is found at high concentrations at sites of inflammation, including RA joints. I am focused on elucidating the role of the novel MIF receptor (CD74) expressing T cells I have identified in mouse models of RA. I am also building on this work to identify the role of CD74 expressing T cells in health and other diseases.
With the COVID pandemic came the widespread use of mRNA vaccines. I am a part of a collaboration to understand the larger immune response, beyond B cells and antibody production, to vaccinations with either an mRNA or a self-amplifying RNA vaccine.
ORCID
0009-0006-0642-8237
Research at a Glance
Publications Timeline
Yale Co-Authors
Joshua Bilsborrow, MD, MHS
Marta Piecychna
Richard Bucala, MD, PhD
Thuy Tran, MD, PhD
Publications
Featured Publications
Increased Mitochondrial Electron Transport Chain Activity at Complex I Is Regulated by N-Acetylcysteine in Lymphocytes of Patients with Systemic Lupus Erythematosus
Doherty E, Oaks Z, Perl A. Increased Mitochondrial Electron Transport Chain Activity at Complex I Is Regulated by N-Acetylcysteine in Lymphocytes of Patients with Systemic Lupus Erythematosus. Antioxidants & Redox Signaling 2014, 21: 56-65. PMID: 24673154, PMCID: PMC4048573, DOI: 10.1089/ars.2013.5702.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPatients' peripheral blood lymphocytesPeripheral blood lymphocytesSLE patientsN-acetylcysteineHealthy donorsOxidative stressT cellsElectron transport chain activityETC complex IMitochondrial ETC complex IMitochondrial dysfunctionSystemic lupus erythematosusLymphocytes of patientsT cell stimulationT cell activationDisease activityLupus erythematosusBlood lymphocytesHealthy controlsMitochondrial electron transport chain activityComplex I activityTherapeutic efficacyPatientsSLEETC activity
2024
CD74 promotes the formation of an immunosuppressive tumor microenvironment in triple-negative breast cancer in mice by inducing the expansion of tolerogenic dendritic cells and regulatory B cells
Pellegrino B, David K, Rabani S, Lampert B, Tran T, Doherty E, Piecychna M, Meza-Romero R, Leng L, Hershkovitz D, Vandenbark A, Bucala R, Becker-Herman S, Shachar I. CD74 promotes the formation of an immunosuppressive tumor microenvironment in triple-negative breast cancer in mice by inducing the expansion of tolerogenic dendritic cells and regulatory B cells. PLOS Biology 2024, 22: e3002905. PMID: 39576827, PMCID: PMC11623796, DOI: 10.1371/journal.pbio.3002905.Peer-Reviewed Original ResearchCitationsAltmetricConceptsTriple-negative breast cancerMacrophage migration inhibitory factorImmunosuppressive tumor microenvironmentTolerogenic dendritic cellsRegulatory B cellsChronic lymphocytic leukemiaTumor microenvironmentDendritic cellsImmune cellsB cellsBreast cancerInfiltration of immune cellsAggressive breast cancer subtypeMassive infiltration of immune cellsLevels of CD74Cytokine macrophage migration inhibitory factorBreast cancer subtypesMigration inhibitory factorBinding to CD74Naive BTol-DCsLymphocytic leukemiaTumor environmentMassive infiltrationCancer subtypes
2019
Macrophage migration inhibitory factor (MIF) as a therapeutic target for rheumatoid arthritis and systemic lupus erythematosus
Bilsborrow JB, Doherty E, Tilstam PV, Bucala R. Macrophage migration inhibitory factor (MIF) as a therapeutic target for rheumatoid arthritis and systemic lupus erythematosus. Expert Opinion On Therapeutic Targets 2019, 23: 733-744. PMID: 31414920, PMCID: PMC6800059, DOI: 10.1080/14728222.2019.1656718.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsMacrophage migration inhibitory factorSystemic lupus erythematosusRheumatoid arthritisMigration inhibitory factorLupus erythematosusMIF inhibitorsMIF inhibitionAutoimmune diseasesRole of MIFInhibitory factorPathogenesis of RARefractory autoimmune diseasesHigh expressionPleiotropic inflammatory cytokineClinical trial dataPrecision medicine approachGlucocorticoid dependenceInflammatory cytokinesAdaptive immunityTherapeutic targetClinical developmentSmall molecule inhibitorsTrial dataTherapeutic potentialErythematosus
2017
Measurement of Mitochondrial Mass by Flow Cytometry during Oxidative Stress.
Doherty E, Perl A. Measurement of Mitochondrial Mass by Flow Cytometry during Oxidative Stress. Reactive Oxygen Species 2017, 4: 275-283. PMID: 29806036, PMCID: PMC5964986, DOI: 10.20455/ros.2017.839.Peer-Reviewed Original ResearchCitations
2012
N‐acetylcysteine reduces disease activity by blocking mammalian target of rapamycin in T cells from systemic lupus erythematosus patients: A randomized, double‐blind, placebo‐controlled trial
Lai Z, Hanczko R, Bonilla E, Caza TN, Clair B, Bartos A, Miklossy G, Jimah J, Doherty E, Tily H, Francis L, Garcia R, Dawood M, Yu J, Ramos I, Coman I, Faraone SV, Phillips PE, Perl A. N‐acetylcysteine reduces disease activity by blocking mammalian target of rapamycin in T cells from systemic lupus erythematosus patients: A randomized, double‐blind, placebo‐controlled trial. Arthritis & Rheumatism 2012, 64: 2937-2946. PMID: 22549432, PMCID: PMC3411859, DOI: 10.1002/art.34502.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsGm/daySLE Disease Activity IndexSystemic lupus erythematosus patientsLupus erythematosus patientsDisease activityFatigue Assessment ScaleT cellsN-acetylcysteineBritish Isles Lupus Assessment Group (BILAG) indexGSH precursor N-acetylcysteineMammalian targetPlacebo-controlled trialDisease activity indexPlacebo-controlled studyAnti-DNA productionLupus disease activityT cell dysfunctionPrecursor N-acetylcysteineDaily placeboReversible nauseaSLEDAI scoreSLE patientsFoxp3 expressionCD4-CD8Cell dysfunctionAssessment of Mitochondrial Dysfunction in Lymphocytes of Patients with Systemic Lupus Erythematosus
Perl A, Hanczko R, Doherty E. Assessment of Mitochondrial Dysfunction in Lymphocytes of Patients with Systemic Lupus Erythematosus. Methods In Molecular Biology 2012, 900: 61-89. PMID: 22933065, DOI: 10.1007/978-1-60761-720-4_4.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsAdenosine DiphosphateAdenosine TriphosphateCaspasesCell SurvivalCells, CulturedChromatography, High Pressure LiquidElectron TransportEnzyme AssaysFlow CytometryGlutathioneHumansHydrogen-Ion ConcentrationIntracellular SpaceLupus Erythematosus, SystemicLymphocyte ActivationMembrane Potential, MitochondrialMitochondriaMolecular BiologyReactive Oxygen SpeciesT-LymphocytesConceptsSystemic lupus erythematosusLupus T cellsLupus erythematosusMitochondrial hyperpolarizationT cellsImmune systemPersistent mitochondrial hyperpolarizationLymphocytes of patientsReactive oxygen intermediate productionT cell activationOxygen intermediate productionT cell receptorActivation-induced apoptosisInner mitochondrial membraneMitochondrial transmembrane potentialTransient ATP depletionDeath of cellsT lymphocytesAbnormal activationEnhanced Ca2Cell activationROI productionCell receptorMammalian targetNitric oxide
2010
Expansion of CD3+/CD4+/CD25+/Foxp3+ T cells in rapamycin-treated lupus patients (143.52)
Perl A, Lai Z, Telarico T, Bartos A, Miklossy G, Hanczko R, Francis L, Tily H, Ramos I, Garcia R, Phillips P, Jimah J, Doherty E. Expansion of CD3+/CD4+/CD25+/Foxp3+ T cells in rapamycin-treated lupus patients (143.52). The Journal Of Immunology 2010, 184: 143.52-143.52. DOI: 10.4049/jimmunol.184.supp.143.52.Peer-Reviewed Original ResearchConceptsSLE patientsT cellsLupus patientsSystemic lupus erythematosus patientsMitochondrial hyperpolarizationFemale SLE patientsFrequency of TregsPrevalence of Foxp3Lupus erythematosus patientsT cell activationSLEDAI scoreHealthy controlsVivo treatmentPatientsB cellsFemale controlsTherapeutic efficacyCell activationMammalian targetVivo expansionMTOR activityRapamycin treatmentPotential mechanismsTregsRapamycin
2009
T-cell and B-cell signaling biomarkers and treatment targets in lupus
Perl A, Fernandez DR, Telarico T, Doherty E, Francis L, Phillips PE. T-cell and B-cell signaling biomarkers and treatment targets in lupus. Current Opinion In Rheumatology 2009, 21: 454-464. PMID: 19550330, PMCID: PMC4047522, DOI: 10.1097/bor.0b013e32832e977c.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsMitochondrial hyperpolarizationMammalian targetSystemic lupus erythematosusLupus erythematosusT cellsB cellsIntracellular signal processingMetabolic checkpointReceptor recyclingTyrosine kinaseIntercellular communicationRapamycin (mTOR) activationSyk kinaseDendritic cell activationExpression of Foxp3Regulatory T cellsAntinuclear autoantibody productionB cell biomarkersRapamycinKinaseAutoantibody productionDendritic cellsPivotal roleCell activationExpressionPrevention of hepatocarcinogenesis and increased susceptibility to acetaminophen-induced liver failure in transaldolase-deficient mice by N-acetylcysteine
Hanczko R, Fernandez DR, Doherty E, Qian Y, Vas G, Niland B, Telarico T, Garba A, Banerjee S, Middleton FA, Barrett D, Barcza M, Banki K, Landas SK, Perl A. Prevention of hepatocarcinogenesis and increased susceptibility to acetaminophen-induced liver failure in transaldolase-deficient mice by N-acetylcysteine. Journal Of Clinical Investigation 2009, 119: 1546-1557. PMID: 19436114, PMCID: PMC2689120, DOI: 10.1172/jci35722.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsLiver failureHepatocellular carcinomaN-acetylcysteineOxidative stressChronic liver cirrhosisPrevention of hepatocarcinogenesisRecent case reportsPotent antioxidant N-acetylcysteineHepatic mitochondrial dysfunctionAntioxidant N-acetylcysteineCD95/Fas-mediated apoptosisLifelong administrationLiver cirrhosisLiver diseaseCase reportC-jun expressionPromising treatmentProtective roleGlutathione levelsHepatocyte apoptosisFas-mediated apoptosisMitochondrial dysfunctionHepatocarcinogenesisATP/ADP ratioLipid hydroperoxides
2008
Molecular mimicry and immunomodulation by the HRES-1 endogenous retrovirus in SLE
Perl A, Nagy G, Koncz A, Gergely P, Fernandez D, Doherty E, Telarico T, Bonilla E, Phillips PE. Molecular mimicry and immunomodulation by the HRES-1 endogenous retrovirus in SLE. Autoimmunity 2008, 41: 287-297. PMID: 18432409, PMCID: PMC5294745, DOI: 10.1080/08916930802024764.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsHRES-1/Rab4Systemic lupus erythematosusEndogenous retrovirusesImmunological synapseKey intracellular transducersTransferrin receptorT cell activationKey molecular linkCommon fragile sitesNormal T cell activationERV proteinsHIV-1Endosome recyclingHRES-1/p28DNA demethylationIntracellular transducersHRES-1Cellular processesDevelopment of SLEMolecular mimicryHuman genomeAbnormal T-cell responsesGene activationHuman endogenous retrovirusesNuclear autoantigens
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