Featured Publications
The circadian neutrophil, inside-out
Ovadia S, Özcan A, Hidalgo A. The circadian neutrophil, inside-out. Journal Of Leukocyte Biology 2023, 113: 555-566. PMID: 36999376, PMCID: PMC10583762, DOI: 10.1093/jleuko/qiad038.Peer-Reviewed Original ResearchStrategies of neutrophil diversification
Palomino-Segura M, Sicilia J, Ballesteros I, Hidalgo A. Strategies of neutrophil diversification. Nature Immunology 2023, 24: 575-584. PMID: 36959290, PMCID: PMC10139675, DOI: 10.1038/s41590-023-01452-x.Peer-Reviewed Original ResearchBehavioural immune landscapes of inflammation
Crainiciuc G, Palomino-Segura M, Molina-Moreno M, Sicilia J, Aragones DG, Li JLY, Madurga R, Adrover JM, Aroca-Crevillén A, Martin-Salamanca S, del Valle AS, Castillo SD, Welch HCE, Soehnlein O, Graupera M, Sánchez-Cabo F, Zarbock A, Smithgall TE, Di Pilato M, Mempel TR, Tharaux PL, González SF, Ayuso-Sacido A, Ng LG, Calvo GF, González-Díaz I, Díaz-de-María F, Hidalgo A. Behavioural immune landscapes of inflammation. Nature 2022, 601: 415-421. PMID: 34987220, PMCID: PMC10022527, DOI: 10.1038/s41586-021-04263-y.Peer-Reviewed Original ResearchCo-option of Neutrophil Fates by Tissue Environments
Ballesteros I, Rubio-Ponce A, Genua M, Lusito E, Kwok I, Fernández-Calvo G, Khoyratty TE, van Grinsven E, González-Hernández S, Nicolás-Ávila JÁ, Vicanolo T, Maccataio A, Benguría A, Li JL, Adrover JM, Aroca-Crevillen A, Quintana JA, Martín-Salamanca S, Mayo F, Ascher S, Barbiera G, Soehnlein O, Gunzer M, Ginhoux F, Sánchez-Cabo F, Nistal-Villán E, Schulz C, Dopazo A, Reinhardt C, Udalova IA, Ng LG, Ostuni R, Hidalgo A. Co-option of Neutrophil Fates by Tissue Environments. Cell 2020, 183: 1282-1297.e18. PMID: 33098771, DOI: 10.1016/j.cell.2020.10.003.Peer-Reviewed Original ResearchConceptsNeutrophil fateDepletion of neutrophilsHematopoietic recoveryVascular repairNeutrophil statesNeutrophil propertiesViral infectionNeutrophilsTarget tissuesHealthy tissueGenotoxic injuryEarly ageMultiple tissuesTissueTissue environmentPhysiological demandsInflammationHematopoietic homeostasisCXCR4LungNon-canonical functionsInjuryCancerInfectionLeukocytesA Network of Macrophages Supports Mitochondrial Homeostasis in the Heart
Nicolás-Ávila JA, Lechuga-Vieco AV, Esteban-Martínez L, Sánchez-Díaz M, Díaz-García E, Santiago DJ, Rubio-Ponce A, Li JL, Balachander A, Quintana JA, Martínez-de-Mena R, Castejón-Vega B, Pun-García A, Través PG, Bonzón-Kulichenko E, García-Marqués F, Cussó L, A-González N, González-Guerra A, Roche-Molina M, Martin-Salamanca S, Crainiciuc G, Guzmán G, Larrazabal J, Herrero-Galán E, Alegre-Cebollada J, Lemke G, Rothlin CV, Jimenez-Borreguero LJ, Reyes G, Castrillo A, Desco M, Muñoz-Cánoves P, Ibáñez B, Torres M, Ng LG, Priori SG, Bueno H, Vázquez J, Cordero MD, Bernal JA, Enríquez JA, Hidalgo A. A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart. Cell 2020, 183: 94-109.e23. PMID: 32937105, DOI: 10.1016/j.cell.2020.08.031.Peer-Reviewed Original ResearchConceptsPhagocytic receptor MertkNetwork of macrophagesVentricular dysfunctionCardiac stressCardiac macrophagesDefective eliminationMetabolic alterationsOrgan functionImpaired autophagyHealthy myocardiumMyocardial tissueMurine heartMacrophagesMetabolic demandsCardiomyocytesMetabolic stabilityHeartAutophagy machineryMitochondrial homeostasisDysfunctional mitochondriaHomeostasisMembranous particlesDysfunctionInflammasomeMyocardium
2024
Recruited atypical Ly6G+ macrophages license alveolar regeneration after lung injury
Ruscitti C, Abinet J, Maréchal P, Meunier M, de Meeûs C, Vanneste D, Janssen P, Dourcy M, Thiry M, Bureau F, Schneider C, Machiels B, Hidalgo A, Ginhoux F, Dewals B, Guiot J, Schleich F, Garigliany M, Bellahcène A, Radermecker C, Marichal T. Recruited atypical Ly6G+ macrophages license alveolar regeneration after lung injury. Science Immunology 2024, 9: eado1227-eado1227. PMID: 39093958, PMCID: PMC7616420, DOI: 10.1126/sciimmunol.ado1227.Peer-Reviewed Original ResearchConceptsLung injuryAlveolar regenerationGranulocyte-macrophage colony-stimulating factorColony-stimulating factorType 2 epithelial cellsAlveolar type 2 epithelial cellsPopulation of macrophagesModels of injuryImmune cellsSuspected pneumoniaA virusAlveolar damageEpithelial regenerationInterleukin-4Lung damageMacrophage subsetsReceptor signalingLungPerilesional areaRepair responseMacrophagesTherapeutic targetInjuryCellsAirborne pathogensResident and recruited macrophages differentially contribute to cardiac healing after myocardial ischemia
Weinberger T, Denise M, Joppich M, Fischer M, Rodriguez C, Kumaraswami K, Wimmler V, Ablinger S, Räuber S, Fang J, Liu L, Liu H, Winterhalter J, Lichti J, Thomas L, Esfandyari D, Percin G, Matin S, Hidalgo A, Waskow C, Engelhardt S, Todica A, Zimmer R, Pridans C, Perdiguero E, Schulz C. Resident and recruited macrophages differentially contribute to cardiac healing after myocardial ischemia. ELife 2024, 12: rp89377. PMID: 38775664, PMCID: PMC11111219, DOI: 10.7554/elife.89377.Peer-Reviewed Original ResearchConceptsInfarct sizeCardiac remodelingI/R injuryMacrophage populationsDeterioration of cardiac functionRecruitment of monocyte-derived macrophagesIschemia/reperfusion (I/R) injuryAntigen-presenting macrophagesImmune cell crosstalkSubsets of macrophagesIncreased infarct sizeMonocyte-derived macrophagesResponse to injuryInfluence infarct sizeContext of myocardial infarctionCSF1R inhibitionCardiac healingCardiac macrophagesCardiac functionCell crosstalkAdverse remodelingResident macrophagesTissue macrophagesMacrophage lineageMyocardial ischemiaResident and recruited macrophages differentially contribute to cardiac healing after myocardial ischemia
Weinberger T, Denise M, Joppich M, Fischer M, Garcia Rodriguez C, Kumaraswami K, Wimmler V, Ablinger S, Räuber S, Fang J, Liu L, Liu W, Winterhalter J, Lichti J, Thomas L, Esfandyari D, Percin G, Matin S, Hidalgo A, Waskow C, Engelhardt S, Todica A, Zimmer R, Pridans C, Gomez Perdiguero E, Schulz C. Resident and recruited macrophages differentially contribute to cardiac healing after myocardial ischemia. ELife 2024, 12 DOI: 10.7554/elife.89377.4.Peer-Reviewed Original ResearchInfarct sizeCardiac remodelingI/R injuryMacrophage populationsDeterioration of cardiac functionRecruitment of monocyte-derived macrophagesIschemia/reperfusion (I/R) injuryAntigen-presenting macrophagesImmune cell crosstalkSubsets of macrophagesIncreased infarct sizeMonocyte-derived macrophagesResponse to injuryInfluence infarct sizeContext of myocardial infarctionCSF1R inhibitionCardiac healingCardiac macrophagesCardiac functionCell crosstalkAdverse remodelingResident macrophagesTissue macrophagesMacrophage lineageMyocardial ischemiaA concept of dual-responsive prodrugs based on oligomerization-controlled reactivity of ester groups: an improvement of cancer cells versus neutrophils selectivity of camptothecin
Klemt I, Reshetnikov V, Dutta S, Bila G, Bilyy R, Cuartero I, Hidalgo A, Wünsche A, Böhm M, Wondrak M, Kunz-Schughart L, Tietze R, Beierlein F, Imhof P, Gensberger-Reigl S, Pischetsrieder M, Körber M, Jost T, Mokhir A. A concept of dual-responsive prodrugs based on oligomerization-controlled reactivity of ester groups: an improvement of cancer cells versus neutrophils selectivity of camptothecin. RSC Medicinal Chemistry 2024, 15: 1189-1197. PMID: 38665843, PMCID: PMC11042170, DOI: 10.1039/d3md00609c.Peer-Reviewed Original ResearchEmbracing cancer complexity: Hallmarks of systemic disease
Swanton C, Bernard E, Abbosh C, André F, Auwerx J, Balmain A, Bar-Sagi D, Bernards R, Bullman S, DeGregori J, Elliott C, Erez A, Evan G, Febbraio M, Hidalgo A, Jamal-Hanjani M, Joyce J, Kaiser M, Lamia K, Locasale J, Loi S, Malanchi I, Merad M, Musgrave K, Patel K, Quezada S, Wargo J, Weeraratna A, White E, Winkler F, Wood J, Vousden K, Hanahan D. Embracing cancer complexity: Hallmarks of systemic disease. Cell 2024, 187: 1589-1616. PMID: 38552609, DOI: 10.1016/j.cell.2024.02.009.Peer-Reviewed Original ResearchConceptsHuman genetic variationSystemic diseaseHallmarks of cancerTumor-related thrombosisGenetic variationGene-environment interactionsCancer-related deathsComplexity of cancerMolecular basisTreat human cancersNervous system interactionsMechanisms of carcinogenesisHuman cancersImprove patient qualityCancer cachexiaSystemic manifestationsTumor micro-Cancer outcomesDistant organsTumor initiationMolecular oncologyTumorPatients' qualityPrevent cancerCancerNeutrophils in Physiology and Pathology
Aroca-Crevillén A, Vicanolo T, Ovadia S, Hidalgo A. Neutrophils in Physiology and Pathology. Annual Review Of Pathology Mechanisms Of Disease 2024, 19: 227-259. PMID: 38265879, PMCID: PMC11060889, DOI: 10.1146/annurev-pathmechdis-051222-015009.Peer-Reviewed Original ResearchDeterministic reprogramming of neutrophils within tumors
Ng M, Kwok I, Tan L, Shi C, Cerezo-Wallis D, Tan Y, Leong K, Calvo G, Yang K, Zhang Y, Jin J, Liong K, Wu D, He R, Liu D, Teh Y, Bleriot C, Caronni N, Liu Z, Duan K, Narang V, Ballesteros I, Moalli F, Li M, Chen J, Liu Y, Liu L, Qi J, Liu Y, Jiang L, Shen B, Cheng H, Cheng T, Angeli V, Sharma A, Loh Y, Tey H, Chong S, Iannacone M, Ostuni R, Hidalgo A, Ginhoux F, Ng L. Deterministic reprogramming of neutrophils within tumors. Science 2024, 383: eadf6493. PMID: 38207030, PMCID: PMC11087151, DOI: 10.1126/science.adf6493.Peer-Reviewed Original Research
2023
Variable selection for nonlinear dimensionality reduction of biological datasets through bootstrapping of correlation networks
Aragones D, Palomino-Segura M, Sicilia J, Crainiciuc G, Ballesteros I, Sánchez-Cabo F, Hidalgo A, Calvo G. Variable selection for nonlinear dimensionality reduction of biological datasets through bootstrapping of correlation networks. Computers In Biology And Medicine 2023, 168: 107827. PMID: 38086138, DOI: 10.1016/j.compbiomed.2023.107827.Peer-Reviewed Original ResearchConceptsDimensionality reductionBiological datasetsFast computation timeHigh-dimensional biological datasetsNetwork bootstrappingMachine learningMassive datasetsUnsupervised scenarioNonlinear dimensionality reductionExplainable modelsUnsupervised settingAvailable algorithmsComputation timeCorrelation networkInformative displayInformative onesDatasetComplex systemsVariable selectionElastic netUniform Manifold ApproximationNetworkManifold approximationStandard onesData analysis3D-Shaped Binders of Unfolded Proteins Inducing Cancer Cell-Specific Endoplasmic Reticulum Stress In Vitro and In Vivo
Klemt I, Varzatskii O, Selin R, Vakarov S, Kovalska V, Bila G, Bilyy R, Voloshin Y, Cuartero I, Hidalgo A, Frey B, Becker I, Friedrich B, Tietze R, Friedrich R, Alexiou C, Ursu E, Rotaru A, Solymosi I, Pérez-Ojeda M, Mokhir A. 3D-Shaped Binders of Unfolded Proteins Inducing Cancer Cell-Specific Endoplasmic Reticulum Stress In Vitro and In Vivo. Journal Of The American Chemical Society 2023, 145: 22252-22264. PMID: 37773090, DOI: 10.1021/jacs.3c08827.Peer-Reviewed Original ResearchEndoplasmic reticulum stressCancer cellsDose-limiting side effectReticulum stressPrimary tumor growthSK-MES-1ER stressBone marrow cellsPromyelocytic leukemia HL-60Acute promyelocytic leukemia HL-60LLC1 cellsActive doseSide effectsER stress inducersTumor growthSuch drugsLeukemia HL-60Normal bloodProteosome inhibitorMarrow cellsT cell leukemia JurkatOvarian carcinoma A2780DrugsROS increaseNormal cellsThe local microenvironment drives activation of neutrophils in human brain tumors
Maas R, Soukup K, Fournier N, Massara M, Galland S, Kornete M, Wischnewski V, Lourenco J, Croci D, Álvarez-Prado Á, Marie D, Lilja J, Marcone R, Calvo G, Santalla Mendez R, Aubel P, Bejarano L, Wirapati P, Ballesteros I, Hidalgo A, Hottinger A, Brouland J, Daniel R, Hegi M, Joyce J. The local microenvironment drives activation of neutrophils in human brain tumors. Cell 2023, 186: 4546-4566.e27. PMID: 37769657, DOI: 10.1016/j.cell.2023.08.043.Peer-Reviewed Original ResearchTumor-associated neutrophilsHuman brain tumorsBrain tumorsTumor necrosis factor alphaDistinct inflammatory signatureOverall immune suppressionBrain metastasis patientsPro-inflammatory mediatorsSoluble inflammatory mediatorsAbundant immune cellsNecrosis factor alphaActivation of neutrophilsTumor-associated macrophagesPro-angiogenic capacityBrain metastasesInflammatory signatureMetastasis patientsInflammatory mediatorsNeutrophil phenotypeImmune suppressionPeripheral bloodBlood neutrophilsDifferent cancer typesImmune cellsBrain microenvironmentProdrugs sequentially activated by reactive oxygen species and hydroxide ions: a possible solution of the neutropenia problem of common anticancer drugs
Klemt I, Reshetnikov V, Cuartero I, Hidalgo A, Mokhir A. Prodrugs sequentially activated by reactive oxygen species and hydroxide ions: a possible solution of the neutropenia problem of common anticancer drugs. Free Radical Biology And Medicine 2023, 201: 20. DOI: 10.1016/j.freeradbiomed.2023.03.095.Peer-Reviewed Original Research
2022
Neutrophils Regulate Bone Formation Via IL-1b Secretion
Wakahashi K, Yu J, Rubio-Ponce A, Culeman S, Krishacoumar B, Scholtysek C, Krönke G, Schlitzer A, Hidalgo A. Neutrophils Regulate Bone Formation Via IL-1b Secretion. Blood 2022, 140: 1261-1262. DOI: 10.1182/blood-2022-167733.Peer-Reviewed Original ResearchMicrobial Metabolites Target Histone Deacetylases to Trigger Vascular Inflammation in Sickle Cell Disease
Torres L, Sidoli S, Li H, De Oliveira S, Frenette P, Hidalgo A, Ito K. Microbial Metabolites Target Histone Deacetylases to Trigger Vascular Inflammation in Sickle Cell Disease. Blood 2022, 140: 435-436. DOI: 10.1182/blood-2022-169203.Peer-Reviewed Original ResearchNeutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease
Petzold T, Zhang Z, Ballesteros I, Saleh I, Polzin A, Thienel M, Liu L, Ain Q, Ehreiser V, Weber C, Kilani B, Mertsch P, Götschke J, Cremer S, Fu W, Lorenz M, Ishikawa-Ankerhold H, Raatz E, El-Nemr S, Görlach A, Marhuenda E, Stark K, Pircher J, Stegner D, Gieger C, Schmidt-Supprian M, Gaertner F, Almendros I, Kelm M, Schulz C, Hidalgo A, Massberg S. Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease. Immunity 2022, 55: 2285-2299.e7. PMID: 36272416, PMCID: PMC9767676, DOI: 10.1016/j.immuni.2022.10.001.Peer-Reviewed Original Research
2020
Programmed ‘disarming’ of the neutrophil proteome reduces the magnitude of inflammation
Adrover JM, Aroca-Crevillén A, Crainiciuc G, Ostos F, Rojas-Vega Y, Rubio-Ponce A, Cilloniz C, Bonzón-Kulichenko E, Calvo E, Rico D, Moro MA, Weber C, Lizasoaín I, Torres A, Ruiz-Cabello J, Vázquez J, Hidalgo A. Programmed ‘disarming’ of the neutrophil proteome reduces the magnitude of inflammation. Nature Immunology 2020, 21: 135-144. PMID: 31932813, PMCID: PMC7223223, DOI: 10.1038/s41590-019-0571-2.Peer-Reviewed Original ResearchConceptsMagnitude of inflammationNeutrophil extracellular trapsNeutrophil proteomeGranule contentsInflammatory injuryRespiratory distressPneumonia patientsExtracellular trapsCell-intrinsic programsProgressive lossHuman neutrophilsNET formationProtein storesNeutrophilsInflammationLungAntimicrobial functionMouse mutantsCircadian cyclePatientsInjuryTime of dayArmamentariumIncidenceSeverity