Esen Sefik, PhD
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Assistant Professor
Biography
Dr. Esen Sefik is an assistant professor in the Department of Immunobiology at Yale University School of Medicine. She received her B.S. from Yale College and her PhD from Harvard University.
During her doctoral training, she explored host-microbe interactions from a tolerogenic perspective, focusing on maintaining tissue-level homeostasis. To investigate how microbiota aid the maturation of the host immune system, she conducted a pioneering large-scale screen. This involved colonizing germ-free mice with individual bacterial strains. Through focused analysis, she uncovered microbiota-dependent transcriptional control mechanisms affecting Foxp3+ regulatory T cells and IL17-producing T cells. Her findings challenged earlier research on Rorγ and Foxp3, suggesting a collaborative rather than competitive regulation, facilitated by microbiota.
During her postdoctoral training, Dr. Sefik used humanized mice to model human-microbe interactions in chronic infectious and inflammatory diseases. She modeled severe COVID-19 in humanized mice, which exhibited persistent lung pathology similar to that in human patients. Mechanistic studies of this model revealed a cascade of events highlighting the unique contributions of human immune cells, particularly macrophages, to lung pathology. These mice also proved to be excellent models for studying fibrotic diseases with microbial etiology.
Various immune and non-immune cells interact to form a coherent system in tissues. Dr. Sefik is interest in how this system fails during chronic infections. Her work emphasizes the delicate balance maintained by host-microbe interactions, a balance critical for immune system development yet vulnerable to the ravages of chronic inflammatory stimuli. Her goal is to continue elucidating these complex biological mechanisms, contributing to our collective knowledge and the potential for therapeutic advancements.
Appointments
Immunobiology
Assistant ProfessorPrimary
Other Departments & Organizations
Education & Training
- PhD
- Harvard University, Immunology (2015)
- BS
- Yale College, Molecular, cellular and developmental biology (2009)
Research
Publications
2025
Linker histone regulates the myeloid versus lymphoid bifurcation of multipotent hematopoietic stem and progenitors
Karatepe K, de Faria B, Zhang J, Chen X, Pinto H, Fyodorov D, Sefik E, Willcockson M, Flavell R, Skoultchi A, Guo S. Linker histone regulates the myeloid versus lymphoid bifurcation of multipotent hematopoietic stem and progenitors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2509412122. PMID: 41118213, PMCID: PMC12582276, DOI: 10.1073/pnas.2509412122.Peer-Reviewed Original ResearchConceptsMyeloid-biased differentiationGenomic regionsChromatin accessibilityLinker histonesLymphoid fateHematopoietic stemResponse to interferon-alphaNucleosome organizationFate choiceGene expressionChromatinAspartyl protease inhibitorMarker genesMolecular mechanism(sMyeloid biasFate biasLymphoid potentialInterferon-alphaProgenitor cellsHSPCsHistoneMolecular scenarioGenesAspartylProtease inhibitorsSclerotic GVHD and Scleroderma Share Dysregulated Gene Expression that is Ameliorated by EREG Therapeutic Antibody
Newton N, Agrawal K, Odell A, Tracy T, Hackett C, Eldrup A, Whitfield M, Martyanov V, Girardi M, Sefik E, Flavell R, Odell I. Sclerotic GVHD and Scleroderma Share Dysregulated Gene Expression that is Ameliorated by EREG Therapeutic Antibody. Blood 2025 PMID: 40961242, DOI: 10.1182/blood.2025029836.Peer-Reviewed Original ResearchScleroderma/systemic sclerosisTherapeutic antibodiesChronic graft-versus-host diseaseSclerotic skinGraft-versus-host diseasePatients' qualityFibrotic diseasesLungs of patientsEndogenous TLR4 ligandsPatients' quality of lifeKnock-In MiceFibrotic skin diseasesAntifibrotic mechanismsSingle-cell transcriptome profilingSkin fibrosisLocalized sclerodermaNeutralizing antibodiesEGFR ligandsEREG expressionTLR4 ligandTIMP1 expressionTLR4 signalingPatient mortalityPatientsType I collagenHumanization of CD47 enables development of functional human neutrophils via postirradiation remodeling of the bone marrow.
Sefik E, Philbrick W, Zhang F, Agrawal K, Van Lee B, Sam J, Karatepe K, Zheng Y, Liang K, Peng S, Mirza H, Rangavajhula A, Simon P, Arun N, Babu P, Eynon E, Chiorazzi M, Shan L, Halene S, Luo H, Rongvaux A, Kluger Y, Flavell R. Humanization of CD47 enables development of functional human neutrophils via postirradiation remodeling of the bone marrow. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2426546122. PMID: 40956886, PMCID: PMC12478129, DOI: 10.1073/pnas.2426546122.Peer-Reviewed Original ResearchConceptsBone marrowHuman CD47Human granulocyte-macrophage progenitorsHuman immune developmentMature human monocytesHuman neutrophilsHumanized mouse modelNeutrophil extracellular trap formationHuman hematopoietic stemGranulocyte-macrophage progenitorsHuman M-CSFHuman immune responseGenetically modified miceResponse to inflammationExtracellular trap formationHuman bone marrowCD47 promoterHuman immune systemPhysiological levelsNK cellsHumanized miceDendritic cellsHematopoietic stemMyeloid lineageHuman hematopoiesisEngineering Mice to Study Human Immunity
Sefik E, Xiao T, Chiorazzi M, Odell I, Zhang F, Agrawal K, Micevic G, Flavell R. Engineering Mice to Study Human Immunity. Annual Review Of Immunology 2025, 43: 451-487. PMID: 40020225, DOI: 10.1146/annurev-immunol-082523-124415.Peer-Reviewed Original ResearchHumanized miceHuman hematopoiesisImmune responseImmune systemHumanized mouse modelHuman hematopoietic stemImmunocompromised murine hostsResident immune cellsHuman immune responseStudy human immunityHuman immune systemIntegration of multi-omicsHematopoietic stemImmune cell growthImmune cellsEngineered MiceProgenitor cellsMouse modelImmunological diseasesMurine hostCancer treatmentPreclinical drugsHuman immunityMiceModel disease
2024
Sensing DNA as danger: The discovery of cGAS
Flavell R, Sefik E. Sensing DNA as danger: The discovery of cGAS. Immunity 2024, 57: 2251-2254. PMID: 39303723, DOI: 10.1016/j.immuni.2024.09.009.Peer-Reviewed Original ResearchThe human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity
Marin-Lopez A, Huck J, Esterly A, Azcutia V, Rosen C, Garcia-Milian R, Sefik E, Vidal-Pedrola G, Raduwan H, Chen T, Arora G, Halene S, Shaw A, Palm N, Flavell R, Parkos C, Thangamani S, Ring A, Fikrig E. The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity. Science Immunology 2024, 9: eadk9872-eadk9872. PMID: 39121194, PMCID: PMC11924945, DOI: 10.1126/sciimmunol.adk9872.Peer-Reviewed Original ResearchConceptsSuppress antiviral responsesArthropod proteinsPathogen replicationAntiviral responseProtein AVertebrate hostsMosquito salivary proteinsUp-regulatedBlood feedingHuman macrophagesPleomorphic effectsSkin infectionsZika virus disseminationInhibit proinflammatory responsesSalivary proteinsProteinNatural ligandWhite blood cellsHuman skin explantsProinflammatory responseMosquito salivaVirus disseminationHuman CD47Salivary factorsArbovirus infectionGene trajectory inference for single-cell data by optimal transport metrics
Qu R, Cheng X, Sefik E, Stanley III J, Landa B, Strino F, Platt S, Garritano J, Odell I, Coifman R, Flavell R, Myung P, Kluger Y. Gene trajectory inference for single-cell data by optimal transport metrics. Nature Biotechnology 2024, 43: 258-268. PMID: 38580861, PMCID: PMC11452571, DOI: 10.1038/s41587-024-02186-3.Peer-Reviewed Original ResearchGene dynamicsGene programTrajectory inferenceBiological processesCell-cell graphDynamics of genesCell trajectory inferenceSingle-cell RNA sequencingSingle-cell dataCell state transitionsMyeloid lineage maturationDynamics of biological processesGene distributionRNA sequencingPseudotemporal orderingGene processingTrajectories of cellsGenesActivity of biological processesTechnical noiseGroups of cellsLineage maturationCellsConstruct cellsSequence
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-6 trans-signaling in a humanized mouse model of scleroderma
Odell I, Agrawal K, Sefik E, Odell A, Caves E, Kirkiles-Smith N, Horsley V, Hinchcliff M, Pober J, Kluger Y, Flavell R. IL-6 trans-signaling in a humanized mouse model of scleroderma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2306965120. PMID: 37669366, PMCID: PMC10500188, DOI: 10.1073/pnas.2306965120.Peer-Reviewed Original ResearchConceptsBone marrow-derived immune cellsIL-6Human hematopoietic stem cellsImmune cellsT cellsScleroderma skinSoluble IL-6 receptorCD8 T cellsHumanized mouse modelPathogenesis of sclerodermaMesenchymal cellsFibroblast-derived IL-6IL-6 receptorIL-6 signalingT cell activationHuman IL-6Human T cellsExpression of collagenFibrosis improvementPansclerotic morpheaHuman endothelial cellsHumanized miceReduced markersSkin graftsHuman CD4Humanized mouse liver reveals endothelial control of essential hepatic metabolic functions
Kaffe E, Roulis M, Zhao J, Qu R, Sefik E, Mirza H, Zhou J, Zheng Y, Charkoftaki G, Vasiliou V, Vatner D, Mehal W, AlcHepNet, Kluger Y, Flavell R. Humanized mouse liver reveals endothelial control of essential hepatic metabolic functions. Cell 2023, 186: 3793-3809.e26. PMID: 37562401, PMCID: PMC10544749, DOI: 10.1016/j.cell.2023.07.017.Peer-Reviewed Original ResearchConceptsMetabolic functionsSpecies-specific interactionsKey metabolic functionsCell-autonomous mechanismsNon-alcoholic fatty liver diseaseMajor metabolic hubNon-parenchymal cellsMetabolic hubHuman hepatocytesMicroenvironmental regulationHuman diseasesHuman-specific aspectsHuman pathologiesHomeostatic processesSpecies mismatchCholesterol uptakeFatty liver diseaseParacrine mannerHuman immuneBile acid conjugationSinusoidal endothelial cellsHepatic metabolic functionMouse liverEndothelial cellsCells
News
News
- July 16, 2025Source: Yale Ventures
Yale's Colton Center for Autoimmunity Announces 2025 Awardees
- August 12, 2024
Protein in Mosquito Saliva Inhibits Host Immune Response
- July 27, 2023
Yale Scientists Identify Immune Cells Critical for Immunologic Memory for Melanoma
- October 21, 2022
New Mouse Model Provides Unprecedented Look at Human Immune System
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