Andrew James Martins, PhD
Assistant ProfessorCards
Appointments
Contact Info
Immunobiology
100 College Street - Room 1155
New Haven, CT 06510
United States
About
Titles
Assistant Professor
Appointments
Immunobiology
Assistant ProfessorPrimary
Other Departments & Organizations
Education & Training
- Postdoctoral Fellow
- National Institute of Allergy and Infectious Diseases (2016)
- PhD
- The University of Western Ontario, Microbiology and Immunology (2011)
- BSc (Hon)
- The University of Windsor, Biological Sciences (2005)
Research
Overview
The Martins lab focuses on understanding human immunology through the lens of systems biology. We aim to enable a deeper analysis of clinical samples by adapting single cell -omics technologies to be feasible across studies with variable sample types, sizes, and with large sample numbers.
We expect that assessment of individual cell states across a wide range of clinical studies will lead to:
- Comprehensive catalogues of cell states and their association with healthy or diseased donor/patient outcomes
- New therapeutic interventions that target cell subset specific phenotypes to fine-tune immune behavior
- Insights into the role of cell state heterogeneity (the variability in cell states in a population of cells) to immune responses.
In addition, we seek to add new methods to assess and mechanistically interrogate single cell behaviors in human samples through dynamic imaging assays and tissue-mimicking culture conditions. Lab projects typically will combine wet bench and computational components and involve collaboration between lab members and with other labs.
Examples of available projects:
- Modification of existing single cell analysis methods to be cheaper and more scalable, to enable application to a wider range of clinical studies.
- Utilizing existing single cell data to generate refined, interpretable cell subset specific gene sets
- In vitro modeling of immune responses and dynamic cell phenotype tracking with in-culture microscopy
Medical Research Interests
Public Health Interests
ORCID
0000-0002-1832-1924
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
John S. Tsang, PhD, MMath
Steven Kleinstein, PhD
Ana Lledo Delgado, MD
J. Nicholas Fisk
Kevan Herold, MD
Paula Preston-Hurlburt
Immunity, Innate
Single-Cell Analysis
Systems Biology
Gene Regulatory Networks
Publications
2025
Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature
Bosticardo M, Dobbs K, Delmonte O, Martins A, Pala F, Kawai T, Kenney H, Magro G, Rosen L, Yamazaki Y, Yu H, Calzoni E, Lee Y, Liu C, Stoddard J, Niemela J, Fink D, Castagnoli R, Ramba M, Cheng A, Riley D, Oikonomou V, Shaw E, Belaid B, Keles S, Al-Herz W, Cancrini C, Cifaldi C, Baris S, Sharapova S, Schuetz C, Gennery A, Freeman A, Somech R, Choo S, Giliani S, Güngör T, Drozdov D, Meyts I, Moshous D, Neven B, Abraham R, El-Marsafy A, Kanariou M, King A, Licciardi F, Cruz-Muñoz M, Palma P, Poli C, Adeli M, Algeri M, Alroqi F, Bastard P, Bergerson J, Booth C, Brett A, Burns S, Butte M, Padem N, de la Morena M, Dbaibo G, de Ravin S, Dimitrova D, Djidjik R, Dorna M, Dutmer C, Elfeky R, Facchetti F, Fuleihan R, Geha R, Gonzalez-Granado L, Haljasmägi L, Ale H, Hayward A, Hifanova A, Ip W, Kaplan B, Kapoor N, Karakoc-Aydiner E, Kärner J, Keller M, Dávila Saldaña B, Kiykim A, Kuijpers T, Kuznetsova E, Latysheva E, Leiding J, Locatelli F, Alva-Lozada G, McCusker C, Celmeli F, Morsheimer M, Ozen A, Parvaneh N, Pasic S, Plebani A, Preece K, Prockop S, Sakovich I, Starkova E, Torgerson T, Verbsky J, Walter J, Ward B, Wisner E, Draper D, Myint-Hpu K, Truong P, Lionakis M, Similuk M, Walkiewicz M, Klion A, Holland S, Oguz C, Bogunovic D, Kisand K, Su H, Tsang J, Kuhns D, Villa A, Rosenzweig S, Pittaluga S, Notarangelo L, Ghosh R, Siefert B, Tokita M, Yan J, Jodarski C, Kamen M, Gore R, Reynolds-Lallement N, Lewis K, Bannon S, Borges A, Gentile N. Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature. Science Immunology 2025, 10: eadq1697. PMID: 39792639, DOI: 10.1126/sciimmunol.adq1697.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsRAG deficiencyRecombination-activating geneImmune dysregulationInflammatory signaturePattern of immune dysregulationT helper 2B cell developmentType I interferonOmenn syndromeImmunological phenotypeImmune profileSelf-antigensB cellsClinical managementDefective TI interferonCellular indicesImmunopathologyPatientsMultiomics approachPhenotypeHypomorphic formDysregulationLineage-specific contributionsDeficiency
2024
Acute and persistent responses after H5N1 vaccination in humans
Apps R, Biancotto A, Candia J, Kotliarov Y, Perl S, Cheung F, Farmer R, Mulè M, Rachmaninoff N, Chen J, Martins A, Shi R, Zhou H, Bansal N, Schum P, Olnes M, Milanez-Almeida P, Han K, Sellers B, Cortese M, Hagan T, Rouphael N, Pulendran B, King L, Manischewitz J, Khurana S, Golding H, van der Most R, Dickler H, Germain R, Schwartzberg P, Tsang J. Acute and persistent responses after H5N1 vaccination in humans. Cell Reports 2024, 43: 114706. PMID: 39235945, PMCID: PMC11949244, DOI: 10.1016/j.celrep.2024.114706.Peer-Reviewed Original ResearchConceptsH5N1 influenza vaccineImpact vaccine responsesTime pointsAdjuvant AS03H5N1 vaccineInfluenza vaccineT cellsVaccine responseVaccinated cohortHigh antibody respondersImmune stateVaccine antigensMultiple time pointsSingle-cell profilingInitial vaccinationSystems immunologyVaccinePersistent responseSurface proteinsCell type-specific signaturesChromatin accessibilityTranscription factorsH5N1DaysAS03Teplizumab induces persistent changes in the antigen‐specific repertoire in individuals at‐risk for type 1 diabetes
Lledó-Delgado A, Preston-Hurlburt P, Currie S, Clark P, Linsley P, Long S, Liu C, Koroleva G, Martins A, Tsang J, Herold K. Teplizumab induces persistent changes in the antigen‐specific repertoire in individuals at‐risk for type 1 diabetes. Journal Of Clinical Investigation 2024, 134: e177492. PMID: 39137044, PMCID: PMC11405034, DOI: 10.1172/jci177492.Peer-Reviewed Original ResearchConceptsCD8+ T cellsAutoreactive T cellsT cellsType 1 diabetesPeripheral blood CD8+ T cellsBlood CD8+ T cellsExpansion of autoreactive T cellsOperational toleranceExpression of CD127Progression of type 1 diabetesAnti-CD3 mAbAntigen-specific repertoireT cell receptorAt-risk patientsAnalysis of study participantsStudy participantsIL7R expressionTeplizumab groupCD8+Placebo groupCD4+Clinical respondersFree intervalTeplizumabReduced expression of genesA unified metric of human immune health
Sparks R, Rachmaninoff N, Lau W, Hirsch D, Bansal N, Martins A, Chen J, Liu C, Cheung F, Failla L, Biancotto A, Fantoni G, Sellers B, Chawla D, Howe K, Mostaghimi D, Farmer R, Kotliarov Y, Calvo K, Palmer C, Daub J, Foruraghi L, Kreuzburg S, Treat J, Urban A, Jones A, Romeo T, Deuitch N, Moura N, Weinstein B, Moir S, Ferrucci L, Barron K, Aksentijevich I, Kleinstein S, Townsley D, Young N, Frischmeyer-Guerrerio P, Uzel G, Pinto-Patarroyo G, Cudrici C, Hoffmann P, Stone D, Ombrello A, Freeman A, Zerbe C, Kastner D, Holland S, Tsang J. A unified metric of human immune health. Nature Medicine 2024, 30: 2461-2472. PMID: 38961223, DOI: 10.1038/s41591-024-03092-6.Peer-Reviewed Original ResearchConceptsClinically healthy individualsHealthy individualsImmune cell frequenciesImmune healthInflammatory biomarkers C-reactive proteinC-reactive proteinBiomarkers C-reactive proteinResponse to immunizationAntibody response to immunizationInflammatory disease statesImmune pathologyDisease activityTreatment responseAntigenic stimulationImmune consequencesClinical dataImmunological pathwaysHealthy controlsCell frequencyInterleukin-6Nonimmunologic diseasesImmune diseasesMonogenic diseasesMonogenic conditionsMedication useIntegrating population and single-cell variations in vaccine responses identifies a naturally adjuvanted human immune setpoint
Mulè M, Martins A, Cheung F, Farmer R, Sellers B, Quiel J, Jain A, Kotliarov Y, Bansal N, Chen J, Schwartzberg P, Tsang J. Integrating population and single-cell variations in vaccine responses identifies a naturally adjuvanted human immune setpoint. Immunity 2024, 57: 1160-1176.e7. PMID: 38697118, DOI: 10.1016/j.immuni.2024.04.009.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsTranscriptional statesVaccine responseSingle-cell profiling methodsSingle-cell variationAS03-adjuvanted vaccineUnadjuvanted influenza vaccineResponse to lipopolysaccharide stimulationB cell signaturesCD14<sup>+</sup> monocytesSingle-cell levelBiological insightsUnadjuvanted vaccineAS03-adjuvantedInfluenza vaccineResponse phenotypesCITE-seqInnate subsetsAdjuvant developmentHigh antibody respondersDay 1Antibody respondersLipopolysaccharide stimulationVaccineCorrelation networkHuman population
2023
Human transcriptional signature of protection after Plasmodium falciparum immunization and infectious challenge via mosquito bites
Mura M, Misganaw B, Gautam A, Robinson T, Chaudhury S, Bansal N, Martins A, Tsang J, Hammamieh R, Bergmann-Leitner E. Human transcriptional signature of protection after Plasmodium falciparum immunization and infectious challenge via mosquito bites. Human Vaccines & Immunotherapeutics 2023, 19: 2282693. PMID: 38010150, PMCID: PMC10760396, DOI: 10.1080/21645515.2023.2282693.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsPeripheral blood mononuclear cellsNon-protected individualsHuman malaria infectionImmune correlatesMalaria infectionVaccine-induced responsesCorrelates of protectionTranscriptomic analysisBlood mononuclear cellsAntigen-specific stimulationTranscriptomic profilesAntigen-specific cellsWhole blood transcriptomic analysesImmune signaturesMalaria vaccineMononuclear cellsInfectious challengeVaccine platformEffective vaccineMosquito bitesLongitudinal time pointsSubunit vaccineInfectious pathogensTranscriptional eventsVaccineTracking B cell responses to the SARS-CoV-2 mRNA-1273 vaccine
de Assis F, Hoehn K, Zhang X, Kardava L, Smith C, Merhebi O, Buckner C, Trihemasava K, Wang W, Seamon C, Chen V, Schaughency P, Cheung F, Martins A, Chiang C, Li Y, Tsang J, Chun T, Kleinstein S, Moir S. Tracking B cell responses to the SARS-CoV-2 mRNA-1273 vaccine. Cell Reports 2023, 42: 112780. PMID: 37440409, PMCID: PMC10529190, DOI: 10.1016/j.celrep.2023.112780.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsMemory B cellsB cell receptorB cellsAtypical memory B cellsInfection-naïve individualsTwo-dose SARSSARS-CoV-2 mRNAB cell responsesAntibody-secreting cellsMonth 6Protective immunityCell responsesCell receptorClonal expansionImmunoglobulin GEarly timepointsLater timepointsPlasmablastsVaccinationCD71TimepointsSurface proteinsCellsMultimodal single-cell analysisMRNAInfluenza vaccination reveals sex dimorphic imprints of prior mild COVID-19
Sparks R, Lau W, Liu C, Han K, Vrindten K, Sun G, Cox M, Andrews S, Bansal N, Failla L, Manischewitz J, Grubbs G, King L, Koroleva G, Leimenstoll S, Snow L, Chen J, Tang J, Mukherjee A, Sellers B, Apps R, McDermott A, Martins A, Bloch E, Golding H, Khurana S, Tsang J. Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19. Nature 2023, 614: 752-761. PMID: 36599369, PMCID: PMC10481789, DOI: 10.1038/s41586-022-05670-5.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsMild COVID-19Control individualsInnate immune genesInfluenza vaccinationCOVID-19Day 28Day 1Viral infectionNon-hospitalized COVID-19Baseline immune statusAcute viral infectionSex-matched control individualsMemory-like CD8IL-15 responsesIL-15 stimulationSex-dimorphic effectsToll-like receptorsFuture immune responseHealthy control individualsImmune genesSystems immunology approachT-cell activation signaturesHealthy male individualsMale individualsMore IFNγ
2022
Adaptive immune responses to SARS-CoV-2 persist in the pharyngeal lymphoid tissue of children
Xu Q, Milanez-Almeida P, Martins A, Radtke A, Hoehn K, Oguz C, Chen J, Liu C, Tang J, Grubbs G, Stein S, Ramelli S, Kabat J, Behzadpour H, Karkanitsa M, Spathies J, Kalish H, Kardava L, Kirby M, Cheung F, Preite S, Duncker P, Kitakule M, Romero N, Preciado D, Gitman L, Koroleva G, Smith G, Shaffer A, McBain I, McGuire P, Pittaluga S, Germain R, Apps R, Schwartz D, Sadtler K, Moir S, Chertow D, Kleinstein S, Khurana S, Tsang J, Mudd P, Schwartzberg P, Manthiram K. Adaptive immune responses to SARS-CoV-2 persist in the pharyngeal lymphoid tissue of children. Nature Immunology 2022, 24: 186-199. PMID: 36536106, PMCID: PMC10777159, DOI: 10.1038/s41590-022-01367-z.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsT cell receptorImmune responseGerminal centersPrevious SARS-CoV-2 infectionSARS-CoV-2 infectionB-cell receptor sequencingTissue-specific immunityCell receptor sequencingAdaptive immune responsesUpper respiratory tractMemory B cellsT cell clonotypesSite of infectionSARS-CoV-2Pharyngeal lymphoid tissuePeripheral bloodLymphocyte populationsLymphoid tissueRespiratory tractCell clonotypesAdaptive immunityB cellsCDR3 sequencesAdenoidsCell receptorNormalizing and denoising protein expression data from droplet-based single cell profiling
Mulè M, Martins A, Tsang J. Normalizing and denoising protein expression data from droplet-based single cell profiling. Nature Communications 2022, 13: 2099. PMID: 35440536, PMCID: PMC9018908, DOI: 10.1038/s41467-022-29356-8.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsProtein expression dataSingle-cell profiling methodsExpression dataSingle-cell profilingOligo-conjugated antibodiesTechnical noiseProtein populationCITE-seqCellular heterogeneityComprehensive dissectionDownstream analysisCell profilingDSBsSingle cellsProtein levelsProtein expressionCell populationsOpen-source R packageProfiling methodProtein countsEmpty dropletsR packageComputational analysisCellsBiological variation
Teaching & Mentoring
Mentoring
SiYi Chen
Graduate student2024 - PresentWen Yuan Tong
Postgrad associate2023 - 2024
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Immunobiology
100 College Street - Room 1155
New Haven, CT 06510
United States