John MacMicking, PhD
Professor of Microbial Pathogenesis and of ImmunobiologyDownloadHi-Res Photo
Cards
Appointments
Microbial Pathogenesis
Primary
Immunobiology
Secondary
Additional Titles
Member, Yale Systems Biology Institute
Investigator, Howard Hughes Medical Institute
Contact Info
Appointments
Microbial Pathogenesis
Primary
Immunobiology
Secondary
Additional Titles
Member, Yale Systems Biology Institute
Investigator, Howard Hughes Medical Institute
Contact Info
Appointments
Microbial Pathogenesis
Primary
Immunobiology
Secondary
Additional Titles
Member, Yale Systems Biology Institute
Investigator, Howard Hughes Medical Institute
Contact Info
About
Titles
Professor of Microbial Pathogenesis and of Immunobiology
Member, Yale Systems Biology Institute; Investigator, Howard Hughes Medical Institute
Biography
John MacMicking is a Howard Hughes Medical Institute (HHMI) Investigator, Professor of Microbial Pathogenesis and Professor of Immunobiology. He trained in synthetic organic chemistry at the Australian National University (B.Sc, 1st Class Honors) where he conducted thesis work in the Department of Immunology & Cell Biology formerly headed by 1996 Nobel Laureate, Peter Doherty, at the John Curtin School of Medical Research.
He then came to the U.S. to pursue Ph.D studies with Carl Nathan in the Immunology program at Cornell University-Sloan-Kettering Institute in New York City before being selected as an HHMI Life Science Research Foundation Fellow at The Rockefeller University to conduct studies with John McKinney.
His doctoral dissertation described the first knockout of an interferon (IFN)-induced defense protein in eukaryotes - inducible nitric oxide synthase (iNOS) - engineered between 1992-1995. It served as an early paradigm for cell-autonomous innate immunity to bacterial, viral and protozoan infections. At Rockefeller University he computationally identified, physically mapped and began functionally characterizing a complete IFN-inducible GTPase superfamily in humans and mice as a new defense network operating against all pathogen classes. For these discoveries he was named a Edward Mallinckrodt Jr Foundation Fellow (2004), Searle Scholar (2005), Cancer Research Institute Investigator (2006), Burroughs-Wellcome Fund Investigator (2008), CCFA Senior Research Awardee (2010), AAF Scholar (2014), and Kenneth Rainin Foundation Innovator (2014). In 2022, he received the Alumni Award of Distinction (Medical Sciences) from Cornell University.
Dr. MacMicking was promoted to Associate Professor in 2010 and tenured in 2014. He was chosen as an HHMI Investigator in 2015 before moving to the Yale Systems Biology Institute in 2017.
Appointments
Microbial Pathogenesis
ProfessorPrimaryImmunobiology
ProfessorSecondary
Other Departments & Organizations
Education & Training
- Assistant Professor (Adjunct)
- The Rockefeller University (2007)
- Research Associate
- The Rockefeller University (2003)
- HHMI LSRF Fellow
- The Rockefeller University (2000)
- Revson Biomedical Fellow
- The Rockefeller University (1998)
- PhD
- Cornell University (1997)
- BSc (Hon)
- Australian National University (1990)
Research
Overview
Medical Research Interests
Cell Biology; Host-Pathogen Interactions; Immunity, Innate; Interferons
ORCID
0000-0002-1734-135X
Research at a Glance
Yale Co-Authors
Frequent collaborators of John MacMicking's published research.
Publications Timeline
A big-picture view of John MacMicking's research output by year.
Research Interests
Research topics John MacMicking is interested in exploring.
Euisoon Park
Erdem Karatekin, PhD
Joerg Bewersdorf, PhD
Craig B. Wilen, MD, PhD
Ellen F Foxman, MD, PhD
Kallol Gupta, PhD
26Publications
10,955Citations
Interferons
Host-Pathogen Interactions
Immunity, Innate
Publications
Featured Publications
Native architecture of a human GBP1 defense complex for cell-autonomous immunity to infection
Zhu S, Bradfield C, Maminska A, Park E, Kim B, Kumar P, Huang S, Kim M, Zhang Y, Bewersdorf J, MacMicking J. Native architecture of a human GBP1 defense complex for cell-autonomous immunity to infection. Science 2024, 383: eabm9903. PMID: 38422126, DOI: 10.1126/science.abm9903.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsGuanylate-binding proteinsCaspase-4Surface of Gram-negative bacteriaGuanosine triphosphate hydrolysisImmunity to infectionInnate immunity to infectionCryo-electron tomographyGram-negative bacteriaImmunity proteinSignaling platformsMembrane insertionHuman cellsNative structureCombat infectionsLipopolysaccharide releaseGasdermin DExtended conformationLiving organismsProteinDefense complexCellsNative architectureGBP1BacteriaInfectionPLSCR1 is a cell-autonomous defence factor against SARS-CoV-2 infection
Xu D, Jiang W, Wu L, Gaudet R, Park E, Su M, Cheppali S, Cheemarla N, Kumar P, Uchil P, Grover J, Foxman E, Brown C, Stansfeld P, Bewersdorf J, Mothes W, Karatekin E, Wilen C, MacMicking J. PLSCR1 is a cell-autonomous defence factor against SARS-CoV-2 infection. Nature 2023, 619: 819-827. PMID: 37438530, PMCID: PMC10371867, DOI: 10.1038/s41586-023-06322-y.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsC-terminal Ī²-barrel domainSpike-mediated fusionCell-autonomous defenseLarge-scale exome sequencingĪ-barrel domainGenome-wide CRISPRSARS-CoV-2 infectionHost cell cytosolScramblase activityPhospholipid scramblaseLive SARS-CoV-2 infectionHuman lung epitheliumPLSCR1SARS-CoV-2 USASingle-molecule switchingSARS-CoV-2 variantsExome sequencingHuman populationRestriction factorsViral RNANew SARS-CoV-2 variantsSARS-CoV-2Robust activityLung epitheliumDefense factorsA human apolipoprotein L with detergent-like activity kills intracellular pathogens
Gaudet RG, Zhu S, Halder A, Kim BH, Bradfield CJ, Huang S, Xu D, MamiƱska A, Nguyen TN, Lazarou M, Karatekin E, Gupta K, MacMicking JD. A human apolipoprotein L with detergent-like activity kills intracellular pathogens. Science 2021, 373 PMID: 34437126, PMCID: PMC8422858, DOI: 10.1126/science.abf8113.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsApolipoproteins LBacterial Outer MembraneBacteriolysisCell MembraneCell Membrane PermeabilityCells, CulturedCRISPR-Cas SystemsCytosolDetergentsGene EditingGram-Negative BacteriaGTP-Binding ProteinsHumansImmunity, InnateInterferon-gammaLipoproteinsMicrobial ViabilityO AntigensProtein DomainsSalmonella typhimuriumSolubilityConceptsSingle-particle cryo-electron microscopyCell-autonomous defenseCytosol-invasive bacteriaExpression of hundredsNative mass spectrometryCryo-electron microscopyHuman genesDetergent-like activityHost proteinsLipoprotein nanodiscsMammalian lipidsExtracellular transportImmune cytokine interferonCell typesDetergent-like propertiesApolipoprotein LLife-threatening infectionsPotent bactericidal agentsAnionic membranesProteinCytokine interferonNonimmune cellsMass spectrometryCellsMutagenesisA phase-separated nuclear GBPL circuit controls immunity in plants
Huang S, Zhu S, Kumar P, MacMicking JD. A phase-separated nuclear GBPL circuit controls immunity in plants. Nature 2021, 594: 424-429. PMID: 34040255, PMCID: PMC8478157, DOI: 10.1038/s41586-021-03572-6.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsArabidopsisCell NucleusChromatinCryoelectron MicroscopyGene Expression Regulation, PlantGTP-Binding ProteinsIntrinsically Disordered ProteinsMediator ComplexMultigene FamilyOrganellesPhase TransitionPlant CellsPlant DiseasesPlant ImmunityPromoter Regions, GeneticRNA Polymerase IITranscription, GeneticConceptsLiquid-liquid phase separationRNA polymerase II machineryMembraneless organellesSitu cryo-electron tomographyDefense gene promotersDiverse cellular activitiesSpecific transcriptional coactivatorsHost gene expressionPhase-separated condensatesCryo-electron tomographyGuanylate-binding proteinsPlant defenseArabidopsis thalianaBiotic stressesAllosteric switchMediator complexTranscriptional responseTranscriptional coactivatorDisease resistanceGene expressionCellular activitiesIndispensable playerBiological importanceOrganellesImmune cuesInterferon-
Casanova J, MacMicking J, Nathan C. Interferon-. Science 2024, 384: eadl2016. PMID: 38635718, DOI: 10.1126/science.adl2016.Peer-Reviewed Original ResearchCitationsAltmetricGuanylate-binding proteins convert cytosolic bacteria into caspase-4 signaling platforms
Wandel MP, Kim BH, Park ES, Boyle KB, Nayak K, Lagrange B, Herod A, Henry T, Zilbauer M, Rohde J, MacMicking JD, Randow F. Guanylate-binding proteins convert cytosolic bacteria into caspase-4 signaling platforms. Nature Immunology 2020, 21: 880-891. PMID: 32541830, PMCID: PMC7381384, DOI: 10.1038/s41590-020-0697-2.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsGuanylate-binding proteinsCaspase-4 activationCaspase-4Human caspase-4Pyroptotic cell deathGram-negative bacteriaCytosolic bacteriaReplicative nicheEvolutionary evidenceIntracellular bacteriaCell deathMultiple antagonistsNeighboring cellsCaspase-11BacteriaAntibacterial defenseBacterial challengeGasderminShigella flexneriProteinDependent pyroptosisActivationPathwayBacterial lipopolysaccharideGBP2Interferon-induced guanylate-binding proteins: Guardians of host defense in health and disease
Tretina K, Park ES, Maminska A, MacMicking JD. Interferon-induced guanylate-binding proteins: Guardians of host defense in health and disease. Journal Of Experimental Medicine 2019, 216: 482-500. PMID: 30755454, PMCID: PMC6400534, DOI: 10.1084/jem.20182031.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsGuanylate-binding proteinsNumerous host cell typesHost cell typesImportant human diseasesCritical rheostatBasic biologyMicrobial pathogensHost defense activitiesHuman diseasesSimilar functionsCell typesHomeostatic settingsGTPasesInnate immunityDefense activitiesHost defenseInflammatory syndromeNeoplastic diseaseClinical approachTissue damageBacterial infectionsCentral orchestratorDiseaseIFNRheostatInterferon-induced guanylate-binding proteins in inflammasome activation and host defense
Kim BH, Chee JD, Bradfield CJ, Park ES, Kumar P, MacMicking JD. Interferon-induced guanylate-binding proteins in inflammasome activation and host defense. Nature Immunology 2016, 17: 481-489. PMID: 27092805, PMCID: PMC4961213, DOI: 10.1038/ni.3440.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsCellular Self-Defense: How Cell-Autonomous Immunity Protects Against Pathogens
Randow F, MacMicking JD, James LC. Cellular Self-Defense: How Cell-Autonomous Immunity Protects Against Pathogens. Science 2013, 340: 701-706. PMID: 23661752, PMCID: PMC3863583, DOI: 10.1126/science.1233028.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsIFN-Inducible GTPases in Host Cell Defense
Kim BH, Shenoy AR, Kumar P, Bradfield CJ, MacMicking JD. IFN-Inducible GTPases in Host Cell Defense. Cell Host & Microbe 2012, 12: 432-444. PMID: 23084913, PMCID: PMC3490204, DOI: 10.1016/j.chom.2012.09.007.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsGuanylate binding proteinsIFN-inducible GTPasesHuman genome-wide association studiesProtein complex assemblyGenome-wide association studiesPathogen-containing vacuolesHost cell defenseVesicular trafficTranscriptional profilingComplex assemblyCell defenseCell-intrinsic responsesAssociation studiesGTPasesBinding proteinCell interiorIndividual cellsAltered expressionGTPase MDiverse groupCentral roleAutophagicCytosolSpeciesPlants
Academic Achievements & Community Involvement
Activities
activity Proceedings National Academy of Sciences USA
2013 - PresentJournal ServiceGuest Editoractivity Journal of Experimental Medicine
07/05/2022 - PresentJournal ServiceAssociate EditorDetailsEditorial Advisory Boardactivity Scientific Advisory Board
09/26/2022 - PresentAdvisory BoardsBoard MemberDetailsSearle Scholars ProgramScientific board memberactivity Cellular Microbiology
2017 - 2021Journal ServiceAssociate EditorDetailsEditorial Advisory Boardactivity American Society of Microbiology (Immunology division)
07/01/2014 - 06/30/2016Professional OrganizationsChairDetailsChair and Chair-Elect, Immunology Division
Honors
honor Alumni Award of Distinction
03/01/2022National AwardCornell UniversityDetailsUnited Stateshonor Investigator
09/01/2015National AwardHoward Hughes Medical Institute (HHMI)DetailsUnited Stateshonor Innovator Award
08/07/2014National AwardKenneth Rainin FoundationDetailsUnited Stateshonor Scholar Award
07/01/2014National AwardAmerican Asthma Foundation (AAF)DetailsUnited Stateshonor Senior Investigator Award
07/01/2010National AwardCrohnās and Colitis Foundation of America (CCFA)DetailsUnited States
News & Links
Media
The human IFN-induced GTPase, GBP1, generates a massive immune defense complex comprising nearly 30,000 conformers on Salmonella typhimurium which serves as a recruitment platform for the inflammasome machinery and other innate immune signaling proteins.
News
- March 11, 2024Source: Yale West Campus
Worldās Most Powerful 3D Super-resolution Microscope Arrives at Yaleās West Campus
- March 01, 2024Source: YaleNews
Discovery of āMolecular Machineā Brings New Immune Therapies a Step Closer
- September 21, 2023Source: HHMI
A Human Protein Found in Non-Immune Cells Defends Against COVID-19
- July 12, 2023Source: YaleNews
Genetic Screen Reveals Protein Primed to Stop COVID-19 Virus
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