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
- Liver Center
- 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 Research Interests
Public Health Interests
ORCID
0000-0002-7045-7837- View Lab Website
Nik Joshi's laboratory
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Kelli Connolly
Gena Gora Foster, MD
Julie F. Cheung
Smita Krishnaswamy, PhD
Eric Fagerberg
Brian G Hunt, PhD
Tumor Microenvironment
T-Lymphocytes, Regulatory
Immunotherapy
Publications
2025
KLF2 maintains lineage fidelity and suppresses CD8 T cell exhaustion during acute LCMV infection
Fagerberg E, Attanasio J, Dien C, Singh J, Kessler E, Abdullah L, Shen J, Hunt B, Connolly K, De Brouwer E, He J, Iyer N, Buck J, Borr E, Damo M, Foster G, Giles J, Huang Y, Tsang J, Krishnaswamy S, Cui W, Joshi N. KLF2 maintains lineage fidelity and suppresses CD8 T cell exhaustion during acute LCMV infection. Science 2025, 387: eadn2337. PMID: 39946463, DOI: 10.1126/science.adn2337.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsCD8 T cellsT cellsCD8 T cell exhaustionNaive CD8 T cellsAcute LCMV infectionT cell exhaustionT cell fate decisionsLineage fidelityLCMV infectionEffector differentiationAcute infectionExhaustion programTranscription factorsImmune responseEpigenetic modulationSuppress differentiationProgenitor stateKLF2InfectionFunctional stateFate decisionsCD8
2024
Mapping the gene space at single-cell resolution with gene signal pattern analysis
Venkat A, Leone S, Youlten S, Fagerberg E, Attanasio J, Joshi N, Perlmutter M, Krishnaswamy S. Mapping the gene space at single-cell resolution with gene signal pattern analysis. Nature Computational Science 2024, 4: 955-977. PMID: 39706866, DOI: 10.1038/s43588-024-00734-0.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsSingle-cell dataGene spaceGene representationSimulated single-cell dataGene co-expression modulesCell-cell graphCharacterization of genesGene-gene interactionsCo-expression modulesCell-cell communicationCellular state spaceSingle-cell resolutionSingle-cell sequencing analysisSequence analysisGenesBiological tasksSpatial transcriptomicsGraph signal processing approachSignal pattern analysisPattern analysisSignal processing approachComputational methodsTranscriptomeMouse Models Enable the Functional Investigation of Tertiary Lymphoid Structures in Cancer
Jeevanandam A, Yin Z, Connolly K, Joshi N. Mouse Models Enable the Functional Investigation of Tertiary Lymphoid Structures in Cancer. Methods In Molecular Biology 2024, 2864: 57-76. PMID: 39527217, DOI: 10.1007/978-1-0716-4184-2_4.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsTertiary lymphoid structuresTertiary lymphoid structure formationSecondary lymphoid organsLymphoid structuresMurine modelFeatures of tertiary lymphoid structuresFunction of tertiary lymphoid structuresMouse modelPersistent inflammatory stimulationAssociated with positive clinical outcomesTissue-specific regulatory mechanismsPositive clinical outcomesPrognostic significanceClinical outcomesGut environmentNonlymphoid tissuesLymphoid aggregatesLymphoid organsMouse lungCancer patientsGenetic sequencesInflammatory stimulationRegulatory mechanismsTherapeutic modulationClinical effortsLactate fermentation intoxicates TILs
Hunt B, Kessler E, Joshi N. Lactate fermentation intoxicates TILs. Nature Immunology 2024, 25: 2176-2177. PMID: 39516647, DOI: 10.1038/s41590-024-02020-7.Peer-Reviewed Original ResearchEndothelial γ-protocadherins inhibit KLF2 and KLF4 to promote atherosclerosis
Joshi D, Coon B, Chakraborty R, Deng H, Yang Z, Babar M, Fernandez-Tussy P, Meredith E, Attanasio J, Joshi N, Traylor J, Orr A, Fernandez-Hernando C, Libreros S, Schwartz M. Endothelial γ-protocadherins inhibit KLF2 and KLF4 to promote atherosclerosis. Nature Cardiovascular Research 2024, 3: 1035-1048. PMID: 39232138, PMCID: PMC11399086, DOI: 10.1038/s44161-024-00522-z.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsMeSH KeywordsAnimalsAtherosclerosisCadherin Related ProteinsCadherinsDisease Models, AnimalEndothelial CellsHuman Umbilical Vein Endothelial CellsHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMiceMice, Inbred C57BLMice, KnockoutPlaque, AtheroscleroticReceptors, NotchSignal TransductionConceptsAtherosclerotic cardiovascular diseaseIntracellular domainNotch intracellular domainTranscription factor KLF2Mechanisms of vascular inflammationAnti-inflammatory programVascular endothelial cellsHost defenseCleavage resultsAntibody blockadeGenetic deletionVascular inflammationViral infectionImmune systemEndothelial cellsCardiovascular diseasePromote atherosclerosisBlood flowKLF2KLF4Suppressive signalsEndotheliumMechanistic studiesIntestinal 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, PMCID: PMC11555782, DOI: 10.1126/sciimmunol.adi7038.Peer-Reviewed Original ResearchMeSH 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
Core Needle Biopsies as an Alternative Source for Ex Vivo Expanded TIL for Adoptive Cell Therapy in Triple-Negative Breast Cancer
Coman M, Pusztai L, Hooley R, Andreveja L, Kim L, Joshi N, Bersenev A, Krause D, Park T. Core Needle Biopsies as an Alternative Source for Ex Vivo Expanded TIL for Adoptive Cell Therapy in Triple-Negative Breast Cancer. Journal Of Immunotherapy 2023, 47: 49-53. PMID: 37991241, DOI: 10.1097/cji.0000000000000495.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesCore needle biopsyTriple-negative breast cancerNeedle biopsyBreast cancerEx vivoT-cell receptor clonalityUltrasound-guided core needle biopsyTriple negative breast cancer tumorsMorbidity of surgeryAdoptive cell therapyBreast cancer tumorsTIL generationAdoptive transferTIL culturesMultiple lesionsCytokine secretionMetastatic cancerSame patientTumor tissueCell therapyPatientsCancer tumorsCancerSurgery1025 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 ResearchScRNA-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 ResearchMeSH 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 samples
Academic Achievements & 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
News & Links
News
- February 27, 2025
The Rules of Immunity: What Decides T Cell Fate
- 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
Related Links
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