Philip Askenase, MD
Professor of Medicine (Immunology)Cards
Contact Info
Allergy & Immunology
200 Leeder Hill Drive, Apt 2402
Hamden, CT 06517
United States
About
Titles
Professor of Medicine (Immunology)
Biography
Dr. Askenase’s immunology accomplishments have been in various fields: Immunochemistry, Cellular Immunity, B Cell and Antibody Responses, Immunoparistology, Basophils, Mast Cells, Serotonin, Leukotrienes, Prostaglandins, IgE receptors, Asthma, iNKT Cells, NK cells, and recently Suppressor / Regulatory T Cells.
Unique B-1 B cell discoveries include their role in T cell immunity; namely contact sensitivity (CS) and delayed-type hypersensitivity (DTH). Current work involves a new regulatory suppressor T cell mechanism involving production of antigen-specific suppressor exosomes with coating of an activated exosome subpopulation with chosen antibody light chains and further their association with particular miRNA for dual antigen and gene specificity.
Appointments
Education & Training
- MD
- Yale University (1965)
- Fellow
- National Institutes of Health
- Fellow
- Yale University School of Medicine
Board Certifications
Allergy & Immunology
- Certification Organization
- AB of Allergy & Immunology
- Original Certification Date
- 1974
Internal Medicine
- Certification Organization
- AB of Internal Medicine
- Original Certification Date
- 1973
Research
Overview
T Cell Mediated Suppression via miRNA in Nanovesicle Exosomes Acting Between Cells.
An immensely exciting project in our laboratory stems from our recent discovery that a T cell suppressive factor (TsF) that inhibits effector Th1 and Th2 cells in vivo, contains an a small RNA. We postulated it that it is a regulatory miRNAthat acts by being transported between cells; from the suppressive/regulatory T cells to target effector T cells via carriage in exosomes. These are nanovesicles (50-150 nm) secreted by all cells, present in all fluids and made in some form by all species down to and including fungi and bacteria suppress immune responses. Remarkably, exosomes contain proteins and RNAsthat target other cells to pass signaling and genetic functional information. Subsequent study in our system, employing affinity columns, Solexa sequencing, knock out mice and bioinformatics, ascertained definitively that it is miRNA-150, that is know to participate in other elements of the immune system. The effect produced is systematic and thus endocrine in nature. Thus, suppressive exosomes can be found in the blood serum of mice tolerized to induce the suppressive T cells that release supernatant of miRNA containing exosomes.
Current clinical efforts are to isolate exosomes in the blood of patients, say with cancer to detect markers of particular tumors as part of “liquiddiagnosis” as adjunct or replacement of biopsies. This cell to cell transfer of active genetic information, here for systemic immune regulation in a mammalian system is unprecedented and paradigm breaking. It is likely that interference with this newly recognized mode of antigen-specific T cell suppression can be used therapeutically, or inhibited with antagomirs where indicated. Antagomirs that block the active Exosome-transferred miRNA could oppose oncogenes or reverse immunosuppression in cancer. Exosomes also could create a new pathway in specific immunotherapy that could compliment existing non-specific treatments, resulting in less toxic side effects, greater specificity, and safer use of higher doses of current non-specific drugs (steroids) and biologics (anti-TNF etc). Alternatively, in vitro alteration of syngeneic exosomes for in vivo therapeutic use to alter immune responses, opens an entirely new avenue of possible immunotherapy. In fact, we also are working with healing exosomes of mesenchymal stem cells for treatment of spinal cord injuries. Finally, detection and analysis of exosomes in the blood is a new method of determining the patient’s immune response.
Overall, the goals of these studies are to determine links between these basic findings in mice with diseases in humans, and to dissect out the participation of the recent discoveries that B1 B cells, serotonin, serum complement and iNKT cells, as well as intercellular nanovesicle exosomes passing regulatory miRNAs between cells, participate in critical interactions leading to T cell effector and regulatory functions that may be harnessed for diagnosis and therapy of a variety of diseases, including allergies, autoimmunity and cancer.
Medical Research Interests
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Erol Fikrig, MD
Jun Lu, PhD
Michael Caplan, PhD, MD
Steven Kleinstein, PhD
Yasuko Iwakiri, PhD
T-Lymphocytes
Exosomes
Publications
2023
Approaches to pandemic prevention – the chromatin vaccine
Zhang J, Askenase P, Jaenisch R, Crumpacker C. Approaches to pandemic prevention – the chromatin vaccine. Frontiers In Immunology 2023, 14: 1324084. PMID: 38143744, PMCID: PMC10739501, DOI: 10.3389/fimmu.2023.1324084.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsConceptsEffective vaccineViral infectionCoronavirus diseaseImmunodeficiency syndromeHIV DNASuccessful vaccinePolio vaccineHIV integrationVaccineNext pandemicViral replicationIneffective vaccinesInfectionEpisomal formFuture pandemicsCurrent pandemicPandemic preventionPreventionPandemicEnd productsEpigenetic silencingSyndromeDiseaseHuman population
2022
Systems Vaccinology in HIV Vaccine Development
Zhang J, Askenase P, Crumpacker C. Systems Vaccinology in HIV Vaccine Development. Vaccines 2022, 10: 1624. PMID: 36298489, PMCID: PMC9611490, DOI: 10.3390/vaccines10101624.Peer-Reviewed Original ResearchCitationsExosome Carrier Effects; Resistance to Digestion in Phagolysosomes May Assist Transfers to Targeted Cells; II Transfers of miRNAs Are Better Analyzed via Systems Approach as They Do Not Fit Conventional Reductionist Stoichiometric Concepts
Askenase PW. Exosome Carrier Effects; Resistance to Digestion in Phagolysosomes May Assist Transfers to Targeted Cells; II Transfers of miRNAs Are Better Analyzed via Systems Approach as They Do Not Fit Conventional Reductionist Stoichiometric Concepts. International Journal Of Molecular Sciences 2022, 23: 6192. PMID: 35682875, PMCID: PMC9181154, DOI: 10.3390/ijms23116192.Peer-Reviewed Original ResearchCitationsAltmetric
2021
Rare Skin Reactions after mRNA Vaccination, Similar to Jones–Mote Basophil Responses
Askenase PW. Rare Skin Reactions after mRNA Vaccination, Similar to Jones–Mote Basophil Responses. New England Journal Of Medicine 2021, 385: 1720-1721. PMID: 34706177, PMCID: PMC8609603, DOI: 10.1056/nejmc2111452.Peer-Reviewed Original ResearchCitationsAltmetricSmall extracellular vesicles released by infused mesenchymal stromal cells target M2 macrophages and promote TGF‐β upregulation, microvascular stabilization and functional recovery in a rodent model of severe spinal cord injury
Nakazaki M, Morita T, Lankford KL, Askenase PW, Kocsis JD. Small extracellular vesicles released by infused mesenchymal stromal cells target M2 macrophages and promote TGF‐β upregulation, microvascular stabilization and functional recovery in a rodent model of severe spinal cord injury. Journal Of Extracellular Vesicles 2021, 10: e12137. PMID: 34478241, PMCID: PMC8408371, DOI: 10.1002/jev2.12137.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsMarrow-derived mesenchymal stem/stromal cellsSpinal cord injuryBlood-spinal cord barrierSmall extracellular vesiclesFunctional recoveryM2 macrophagesCord injuryInjury siteTherapeutic effectStromal cellsSevere spinal cord injurySingle MSC injectionImproved functional recoveryBone marrow-derived mesenchymal stem/stromal cellsM2 macrophage markersSimilar therapeutic effectsRelease of sEVsMesenchymal stem/stromal cellsExtracellular vesiclesTight junction proteinsStem/stromal cellsMesenchymal stromal cellsTGF-β receptorMSC infusionSCI ratsAntibodies Enhance the Suppressive Activity of Extracellular Vesicles in Mouse Delayed-Type Hypersensitivity
Nazimek K, Bustos-Morán E, Blas-Rus N, Nowak B, Totoń-Żurańska J, Seweryn MT, Wołkow P, Woźnicka O, Szatanek R, Siedlar M, Askenase PW, Sánchez-Madrid F, Bryniarski K. Antibodies Enhance the Suppressive Activity of Extracellular Vesicles in Mouse Delayed-Type Hypersensitivity. Pharmaceuticals 2021, 14: 734. PMID: 34451831, PMCID: PMC8398949, DOI: 10.3390/ph14080734.Peer-Reviewed Original ResearchCitationsAltmetricConceptsDelayed-type hypersensitivityMice delayed-type hypersensitivityAntigen-specific antibodiesEffector T cellsT cellsSuppressive activityExtracellular vesiclesAntigen-presenting macrophagesMHC class IIGreat therapeutic potentialMouse modelSuppressive actionCurrent studyMiRNA-150Therapeutic potentialClass IIFlow cytometryExact mechanismAntibodiesParental cellsTherapeutic usageHypersensitivityMacrophagesIntercellular communicationSpecific bindingExosomes provide unappreciated carrier effects that assist transfers of their miRNAs to targeted cells; I. They are ‘The Elephant in the Room’
Askenase PW. Exosomes provide unappreciated carrier effects that assist transfers of their miRNAs to targeted cells; I. They are ‘The Elephant in the Room’. RNA Biology 2021, 18: 2038-2053. PMID: 33944671, PMCID: PMC8582996, DOI: 10.1080/15476286.2021.1885189.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsExtracellular vesiclesAcceptor cellsOuter membrane vesiclesMiRNA transferMolecular chemical changesNano-extracellular vesiclesCargo moleculesExosome transferMembrane vesiclesMiRNAsGenetic expressionDNA expressionExosomesVesiclesCell functionIntracellular effectsFunctional effectsFunctional alterationsMolecular transferCellsPhysiologic processesLight chainExpressionMitochondriaBiology
2013
Antigen-specific, antibody-coated, exosome-like nanovesicles deliver suppressor T-cell microRNA-150 to effector T cells to inhibit contact sensitivity
Bryniarski K, Ptak W, Jayakumar A, Püllmann K, Caplan MJ, Chairoungdua A, Lu J, Adams BD, Sikora E, Nazimek K, Marquez S, Kleinstein SH, Sangwung P, Iwakiri Y, Delgato E, Redegeld F, Blokhuis BR, Wojcikowski J, Daniel AW, Kormelink T, Askenase PW. Antigen-specific, antibody-coated, exosome-like nanovesicles deliver suppressor T-cell microRNA-150 to effector T cells to inhibit contact sensitivity. Journal Of Allergy And Clinical Immunology 2013, 132: 170-181.e9. PMID: 23727037, PMCID: PMC4176620, DOI: 10.1016/j.jaci.2013.04.048.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCutaneous contact sensitivityEffector T cellsT cell toleranceT cellsExosome-like nanovesiclesContact sensitivityCS-effector T cellsMiRNA-150Regulatory T cellsAntigen-specific mannerSuppressor T cellsRole of antibodiesAdoptive cell transfer modelCell transfer modelT cell regulationLight chainSuppressor cellsLymph nodesReactive haptenImmune suppressionMicroRNA-150Systemic injectionAntibody light chainIntravenous injectionSpleen cells
2011
Stimulatory Lipids Accumulate in the Mouse Liver within 30 min of Contact Sensitization to Facilitate the Activation of Naïve iNKT Cells in a CD1d‐Dependent Fashion
Dey N, Szczepanik M, Lau K, Majewska‐Szczepanik M, Askenase PW. Stimulatory Lipids Accumulate in the Mouse Liver within 30 min of Contact Sensitization to Facilitate the Activation of Naïve iNKT Cells in a CD1d‐Dependent Fashion. Scandinavian Journal Of Immunology 2011, 74: 52-61. PMID: 21352253, DOI: 10.1111/j.1365-3083.2011.02540.x.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsHepatic iNKT cellsINKT cellsContact sensitivityHepatic lipidsT cellsB cellsNatural killer T cellsAdoptive transfer techniquesEffector T cellsLiver mononuclear cellsCutaneous inflammatory responseINKT cell activationKiller T cellsMouse liverΑβ T cell receptorAllergic contact dermatitisInnate immune systemRecipient mouse liversSame allergenContact hypersensitivityTopical sensitizationContact sensitizationIgM antibodiesMononuclear cellsIL-4Participation of Inkt Cells in the Early and Late Components of Tc1‐Mediated DNFB Contact Sensitivity: Cooperative Role of γδ‐T Cells
Askenase PW, Majewska‐Szczepanik M, Kerfoot S, Szczepanik M. Participation of Inkt Cells in the Early and Late Components of Tc1‐Mediated DNFB Contact Sensitivity: Cooperative Role of γδ‐T Cells. Scandinavian Journal Of Immunology 2011, 73: 465-477. PMID: 21272050, DOI: 10.1111/j.1365-3083.2011.02522.x.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsMeSH KeywordsAdoptive TransferAnimalsDermatitis, ContactDinitrofluorobenzeneFemaleFlow CytometryImmunizationImmunophenotypingInterferon-gammaMiceMice, Inbred BALB CMice, Inbred C57BLMice, Inbred CBAMice, KnockoutNatural Killer T-CellsReceptors, Antigen, T-Cell, alpha-betaSpecific Pathogen-Free OrganismsT-Lymphocytes, Cytotoxic
News
News
- June 13, 2023Source: Wiley Online Library
Legends of Allergy and Immunology: Philip W. Askenase
- October 11, 2022Source: Research Features
Immunologist Dr. Philip Askenase discusses an innovative new therapy for treating long-COVID
- September 15, 2022
Discoveries & Impact (September 2022)
- November 09, 2021
Discoveries & Impact, November 2021
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Allergy & Immunology
200 Leeder Hill Drive, Apt 2402
Hamden, CT 06517
United States