Nikhil Joshi, PhD
Associate Professor TenureCards
Appointments
Contact Info
Immunobiology
Department of Immunobiology, PO Box 208011, 300 Cedar Street
New Haven, CT 06520
United States
About
Titles
Associate Professor Tenure
Biography
The Joshi laboratory uses intricate tumor models and advanced approaches to investigate immune cell interactions with developing tumors. The goal is to determine mechanistically why these interactions do not lead to more potent anti-tumor responses and to identify entry points for modulating these interactions through genetic manipulation and therapeutic intervention. Our studies focus on using established complex mouse models to investigate how subtypes of T cells function in the tumor microenvironment and how their interactions with other immune cell types impacts tumor development. Our laboratory combines advanced genetic modeling of mice and immunologic techniques to address fundamental questions in tumor immunology.
Appointments
Immunobiology
Associate Professor TenurePrimary
Other Departments & Organizations
- Cancer Immunology
- Discovery to Cure Internship
- Human and Translational Immunology Program
- Immunobiology
- Immunology
- Molecular Medicine, Pharmacology, and Physiology
- Yale Cancer Center
- Yale Center for Immuno-Oncology
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- Yale-UPR Integrated HIV Basic and Clinical Sciences Initiative
Education & Training
- Postdoctoral Fellow
- Massachusetts Institute of Technology (2016)
- PhD
- Yale University, Immunobiology (2009)
- ScM
- Johns Hopkins School of Public Health (2003)
- BS
- University of Michigan (2000)
Research
Overview
Medical Subject Headings (MeSH)
- View Lab Website
Nik Joshi's laboratory
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Julie F. Cheung
Kelli Connolly
Yevgeniya Gora Foster, MD
Harriet Kluger, MD
Jiawei Wang, PhD
Joseph Craft, MD
Tumor Microenvironment
T-Lymphocytes, Regulatory
Immunotherapy
Publications
2024
Intestinal tuft cell immune privilege enables norovirus persistence
Strine M, Fagerberg E, Darcy P, Barrón G, Filler R, Alfajaro M, D'Angelo-Gavrish N, Wang F, Graziano V, Menasché B, Damo M, Wang Y, Howitt M, Lee S, Joshi N, Mucida D, Wilen C. Intestinal tuft cell immune privilege enables norovirus persistence. Science Immunology 2024, 9: eadi7038. PMID: 38517952, DOI: 10.1126/sciimmunol.adi7038.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsConceptsCD8<sup>+</sup> T cellsIntestinal tuft cellsT cellsTufted cellsViral persistenceSite of viral persistenceChemosensory epithelial cellsNormal antigen presentationImmune-privileged nicheIntestinal stem cellsMemory phenotypeImmune privilegeImmune escapeReporter miceAntigen presentationChronic infectionCytotoxic capacityEpithelial cellsNorovirus infectionStem cellsCell interactionsInfectionCell survivalEnteric microbesCells
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 ResearchCancer- and infection-induced T cell exhaustion are distinct
Buck J, Joshi N. Cancer- and infection-induced T cell exhaustion are distinct. Nature Immunology 2023, 24: 1604-1605. PMID: 37709988, DOI: 10.1038/s41590-023-01624-9.Peer-Reviewed Original ResearchAltmetricScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis
Mann J, Lucca L, Austin M, Merkin R, Robert M, Al Bawardy B, Raddassi K, Aizenbud L, Joshi N, Hafler D, Abraham C, Herold K, Kluger H. ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis. Journal For ImmunoTherapy Of Cancer 2023, 11: e007358. PMID: 37586769, PMCID: PMC10432652, DOI: 10.1136/jitc-2023-007358.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsImmune checkpoint inhibitorsT cell subsetsCheckpoint inhibitorsImmune environmentImmune checkpoint inhibitor-induced colitisCheckpoint inhibitor-induced colitisPeripheral immune environmentsStages of colitisTreatment of colitisMerkel cell carcinomaT cell populationsPeripheral blood samplesCourse of progressionT cell receptorMultiple tumor typesAlternative cancer therapyCommon toxicitiesICI colitisTreatment discontinuationAdverse eventsBiologic therapyImmune suppressionCell carcinomaColitisBlood samplesPD-1 maintains CD8 T cell tolerance towards cutaneous neoantigens
Damo M, Hornick N, Venkat A, William I, Clulo K, Venkatesan S, He J, Fagerberg E, Loza J, Kwok D, Tal A, Buck J, Cui C, Singh J, Damsky W, Leventhal J, Krishnaswamy S, Joshi N. PD-1 maintains CD8 T cell tolerance towards cutaneous neoantigens. Nature 2023, 619: 151-159. PMID: 37344588, PMCID: PMC10989189, DOI: 10.1038/s41586-023-06217-y.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsEffector CD8 T cellsCD8 T cellsAntigen-specific effector CD8 T cellsAntigen-specific CD8 T cellsAntigen-expressing cellsT cell tolerancePD-1T cellsAdverse eventsCell toleranceCD8 T cell toleranceImmune-related adverse eventsPeripheral T cell repertoirePeripheral T cell toleranceNon-lesional skinT cell repertoireT-cell antigensPeripheral toleranceCheckpoint receptorsSkin biopsiesLocal infiltrationLocal pathologyCell repertoireMouse modelSkin toleranceT follicular helper cells in cancer, tertiary lymphoid structures, and beyond
Cui C, Craft J, Joshi N. T follicular helper cells in cancer, tertiary lymphoid structures, and beyond. Seminars In Immunology 2023, 69: 101797. PMID: 37343412, DOI: 10.1016/j.smim.2023.101797.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCitationsAltmetricMeSH Keywords and ConceptsConceptsTumor-associated tertiary lymphoid structuresFollicular helper cellsCD8 T cellsTertiary lymphoid structuresSecondary lymphoid organsT cellsHelper cellsLymphoid structuresImmune cellsB cellsCD4 T follicular helper cellsT Follicular Helper CellsTumor-infiltrating immune cellsCurrent immunotherapy regimensCheckpoint blockade immunotherapyCD4 T cellsImmune cell componentsLimited response rateFunctional immune cellsNovel therapeutic targetPotential therapeutic benefitT cell-B cell interactionsBlockade immunotherapyImmunotherapy regimensLymphoid organsMapping the gene space at single-cell resolution with gene signal pattern analysis
Venkat A, Damo M, Joshi N, Krishnaswamy S. Mapping the gene space at single-cell resolution with gene signal pattern analysis. The Journal Of Immunology 2023, 210: 251.03-251.03. DOI: 10.4049/jimmunol.210.supp.251.03.Peer-Reviewed Original ResearchConceptsGene-gene relationshipsGene spaceSingle-cell RNA sequencing analysisGene signalsSingle-cell resolutionRNA sequencing analysisMelanoma patient samplesScRNA-seq analysisTranscriptional programsCellular heterogeneityGene representationSequencing analysisCell typesSingle cellsPattern analysisCell subtypesCell subpopulationsMultiscale viewEffector functionsCellsMouse modelComputational methodsGenesCell spacePatient samples
2022
Novel Mouse Models for Cancer Immunology
Connolly K, Fitzgerald B, Damo M, Joshi N. Novel Mouse Models for Cancer Immunology. Annual Review Of Cancer Biology 2022, 6: 1-23. PMID: 36875867, PMCID: PMC9979244, DOI: 10.1146/annurev-cancerbio-070620-105523.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCitationsAltmetric
2021
Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses
Cui C, Wang J, Fagerberg E, Chen PM, Connolly KA, Damo M, Cheung JF, Mao T, Askari AS, Chen S, Fitzgerald B, Foster GG, Eisenbarth SC, Zhao H, Craft J, Joshi NS. Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses. Cell 2021, 184: 6101-6118.e13. PMID: 34852236, PMCID: PMC8671355, DOI: 10.1016/j.cell.2021.11.007.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCD8 TB cellsTfh cellsLung adenocarcinomaTfh-B cell interactionsTumor-specific B cellsFollicular helper cellsAnti-tumor immunityB cell signaturesCell effector functionsGerminal center formationGC B cellsCD4 THelper cellsTumor controlTumor neoantigensEffector functionsCell collaborationCell responsesCell signatureTumor cellsSignature correlatesNeoantigensCell functionCD4A mouse model for the study of anti-tumor T cell responses in Kras-driven lung adenocarcinoma
Fitzgerald B, Connolly KA, Cui C, Fagerberg E, Mariuzza DL, Hornick NI, Foster GG, William I, Cheung JF, Joshi NS. A mouse model for the study of anti-tumor T cell responses in Kras-driven lung adenocarcinoma. Cell Reports Methods 2021, 1: 100080. PMID: 34632444, PMCID: PMC8500377, DOI: 10.1016/j.crmeth.2021.100080.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsLung adenocarcinomaNeoantigen expressionTumor-specific CD8 T cellsCD8 T cellsImmune checkpoint therapyInfection-induced inflammationExpression of neoantigensCommon lung cancerLUAD cell linesCheckpoint therapyLung cancerTherapeutic responseT cellsImmune responseMouse modelCell responsesTumor inductionTumorsAdenocarcinomaCell linesNeoantigensKrasFuture studiesExpressionImmunotherapy
Academic Achievements and Community Involvement
honor Class of 1961 Cancer Research Award
Yale School of Medicine AwardYale Cancer CenterDetails01/05/2023United Stateshonor Basic Science Research Prize
Yale School of Medicine AwardYale Cancer CenterDetails01/05/2023United Stateshonor Young Investigators in Cancer Research
National AwardPershing Square Sohn PrizeDetails06/27/2022United Stateshonor Emerging Leader Award
National AwardMark FoundationDetails01/01/2022United Stateshonor James B. Dougherty MD Award
National AwardLung Cancer Research FoundationDetails12/01/2021United States
Links & Media
News
- April 12, 2024
Yale Cancer Center Faculty and Trainees Present at AACR Annual Meeting
- July 27, 2023
Yale Scientists Identify Immune Cells Critical for Immunologic Memory for Melanoma
- June 21, 2023
Study Hints at How Cancer Immunotherapy Can Be Safer
- January 10, 2023
Class of 1961 Cancer Research Awards Announced
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Get In Touch
Contacts
Immunobiology
Department of Immunobiology, PO Box 208011, 300 Cedar Street
New Haven, CT 06520
United States
Administrative Support
Locations
Joshi Laboratory
Lab
The Anlyan Center
300 Cedar Street, Ste S640
New Haven, CT 06519
The Anlyan Center
Academic Office
300 Cedar Street, Ste S641B
New Haven, CT 06519