Dr. Kagan's research focuses on understanding the organization of signal transduction pathways within cells of the mammalian immune system. As a model, he focuses his attention on members of the Toll-like Receptor family (TLR) family of proteins. TLRs play a critical role in the detection and elimination of infectious microorganisms that enter the human body. Signaling events that occur downstream from TLR-mediated microbial detection are the primary source of interest to the Kagan lab. Understanding the assembly and regulation of these signaling complexes is directly relevant to the study of human infections, autoimmunity and cancer.

The goals of Dr. Kagan's research include: Understanding the organization and recruitment of signaling proteins to active Toll-like Receptors in professional antigen presenting cells Understanding the molecular mechanisms governing crosstalk between functionally related signaling pathways in the human immune system Understanding how microbial pathogens can manipulate TLR signaling to promote their colonization and dissemination



Jonathan Kagan trained with Craig Roy, receiving his Ph.D. in Microbial Pathogenesis from Yale University. He then performed postdoctoral training with Ruslan Medzhitov in the Immunobiology Department at the Yale University School of Medicine.


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  1. Deep-sea microbes as tools to refine the rules of innate immune pattern recognition. Sci Immunol. 2021 Mar 12; 6(57). View abstract
  2. Inflammasomes within Hyperactive Murine Dendritic Cells Stimulate Long-Lived T Cell-Mediated Anti-tumor Immunity. Cell Rep. 2020 Nov 17; 33(7):108381. View abstract
  3. Mitochondrial Reactive Oxygen Species Participate in Signaling Triggered by Heme in Macrophages and upon Hemolysis. J Immunol. 2020 11 15; 205(10):2795-2805. View abstract
  4. HDAC6 mediates an aggresome-like mechanism for NLRP3 and pyrin inflammasome activation. Science. 2020 09 18; 369(6510). View abstract
  5. Toll-like Receptors and the Control of Immunity. Cell. 2020 03 19; 180(6):1044-1066. View abstract
  6. Asymmetric distribution of TLR3 leads to a polarized immune response in human intestinal epithelial cells. Nat Microbiol. 2020 01; 5(1):181-191. View abstract
  7. Gasdermin D activity in inflammation and host defense. Sci Immunol. 2019 09 06; 4(39). View abstract
  8. Inflammasomes: Threat-Assessment Organelles of the Innate Immune System. Immunity. 2019 10 15; 51(4):609-624. View abstract
  9. Patterns, dynamics and consequences of microplastic ingestion by the temperate coral, Astrangia poculata. Proc Biol Sci. 2019 06 26; 286(1905):20190726. View abstract
  10. Lipids that directly regulate innate immune signal transduction. Innate Immun. 2020 01; 26(1):4-14. View abstract
  11. Host-Encoded Sensors of Bacteria: Our Windows into the Microbial World. Microbiol Spectr. 2019 05; 7(3). View abstract
  12. Modular Architecture of the STING C-Terminal Tail Allows Interferon and NF-?B Signaling Adaptation. Cell Rep. 2019 04 23; 27(4):1165-1175.e5. View abstract
  13. Innate Immune Signaling Organelles Display Natural and Programmable Signaling Flexibility. Cell. 2019 04 04; 177(2):384-398.e11. View abstract
  14. Phosphoinositide Interactions Position cGAS at the Plasma Membrane to Ensure Efficient Distinction between Self- and Viral DNA. Cell. 2019 03 07; 176(6):1432-1446.e11. View abstract
  15. Defying Death: The (W)hole Truth about the Fate of GSDMD Pores. Immunity. 2019 01 15; 50(1):15-17. View abstract
  16. Vector Immunity and Evolutionary Ecology: The Harmonious Dissonance. Trends Immunol. 2018 11; 39(11):862-873. View abstract
  17. The Fly Way of Antiviral Resistance and Disease Tolerance. Adv Immunol. 2018; 140:59-93. View abstract
  18. An Antiviral Branch of the IL-1 Signaling Pathway Restricts Immune-Evasive Virus Replication. Mol Cell. 2018 09 06; 71(5):825-840.e6. View abstract
  19. Retraction Notice to: The Unfolded Protein Response Element IRE1a Senses Bacterial Proteins Invading the ER to Activate RIG-I and Innate Immune Signaling. . 2018 04 11; 23(4):571. View abstract
  20. STING-dependent translation inhibition restricts RNA virus replication. Proc Natl Acad Sci U S A. 2018 02 27; 115(9):E2058-E2067. View abstract
  21. Biochemical Isolation of the Myddosome from Murine Macrophages. Methods Mol Biol. 2018; 1714:79-95. View abstract
  22. The Pore-Forming Protein Gasdermin D Regulates Interleukin-1 Secretion from Living Macrophages. Immunity. 2018 01 16; 48(1):35-44.e6. View abstract
  23. By Capturing Inflammatory Lipids Released from Dying Cells, the Receptor CD14 Induces Inflammasome-Dependent Phagocyte Hyperactivation. Immunity. 2017 10 17; 47(4):697-709.e3. View abstract
  24. How Inflammasomes Inform Adaptive Immunity. J Mol Biol. 2018 01 19; 430(2):217-237. View abstract
  25. Type III IFNs Are Commonly Induced by Bacteria-Sensing TLRs and Reinforce Epithelial Barriers during Infection. J Immunol. 2017 11 01; 199(9):3270-3279. View abstract
  26. Environmental Stress Causes Lethal Neuro-Trauma during Asymptomatic Viral Infections. . 2017 Jul 12; 22(1):48-60.e5. View abstract
  27. Apoptosis and Necroptosis as Host Defense Strategies to Prevent Viral Infection. Trends Cell Biol. 2017 11; 27(11):800-809. View abstract
  28. Innate Immune Receptors as Competitive Determinants of Cell Fate. Mol Cell. 2017 Jun 15; 66(6):750-760. View abstract
  29. Lipopolysaccharide Detection across the Kingdoms of Life. Trends Immunol. 2017 10; 38(10):696-704. View abstract
  30. Multi-receptor detection of individual bacterial products by the innate immune system. Nat Rev Immunol. 2017 Jun; 17(6):376-390. View abstract
  31. Activation and pathogenic manipulation of the sensors of the innate immune system. Microbes Infect. 2017 Apr - May; 19(4-5):229-237. View abstract
  32. Microbe-inducible trafficking pathways that control Toll-like receptor signaling. Traffic. 2017 01; 18(1):6-17. View abstract
  33. Early innate immune responses to bacterial LPS. Curr Opin Immunol. 2017 Feb; 44:14-19. View abstract
  34. Biomarkers of Environmental Enteropathy, Inflammation, Stunting, and Impaired Growth in Children in Northeast Brazil. PLoS One. 2016; 11(9):e0158772. View abstract
  35. A one-protein signaling pathway in the innate immune system. Sci Immunol. 2016 Aug 19; 1(2):eaah6184. View abstract
  36. Editorial overview: Emerging concepts in host-virus interactions. Curr Opin Microbiol. 2016 08; 32:xii-xiii. View abstract
  37. Control of the innate immune response by the mevalonate pathway. Nat Immunol. 2016 08; 17(8):922-9. View abstract
  38. Peroxisomes are platforms for cytomegalovirus' evasion from the cellular immune response. Sci Rep. 2016 05 16; 6:26028. View abstract
  39. Assessing Clinical Research Capacity in Vietnam: A Framework for Strengthening Capability for Clinical Trials in Developing Countries. Public Health Rep. 2016 May-Jun; 131(3):396-403. View abstract
  40. An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells. Science. 2016 Jun 03; 352(6290):1232-6. View abstract
  41. Hepatitis C virus NS3-4A inhibits the peroxisomal MAVS-dependent antiviral signalling response. J Cell Mol Med. 2016 Apr; 20(4):750-7. View abstract
  42. A Single Bacterial Immune Evasion Strategy Dismantles Both MyD88 and TRIF Signaling Pathways Downstream of TLR4. . 2015 Dec 09; 18(6):682-93. View abstract
  43. Mechanisms of Toll-like Receptor 4 Endocytosis Reveal a Common Immune-Evasion Strategy Used by Pathogenic and Commensal Bacteria. Immunity. 2015 Nov 17; 43(5):909-22. View abstract
  44. PRRs are watching you: Localization of innate sensing and signaling regulators. Virology. 2015 May; 479-480:104-9. View abstract
  45. The unique regulation and functions of type III interferons in antiviral immunity. Curr Opin Virol. 2015 Jun; 12:47-52. View abstract
  46. Microbial strategies for antagonizing Toll-like-receptor signal transduction. Curr Opin Immunol. 2015 Feb; 32:61-70. View abstract
  47. Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol. 2015; 33:257-90. View abstract
  48. ACT2 peer-driven intervention increases enrollment into HIV/AIDS medical studies among African Americans/Blacks and Hispanics: A cluster randomized controlled trial. AIDS Behav. 2014 Dec; 18(12):2409-22. View abstract
  49. Emerging principles governing signal transduction by pattern-recognition receptors. Cold Spring Harb Perspect Biol. 2014 Nov 13; 7(3):a016253. View abstract
  50. SMOCs: supramolecular organizing centres that control innate immunity. Nat Rev Immunol. 2014 12; 14(12):821-6. View abstract
  51. Common mechanisms activate plant guard receptors and TLR4. Trends Immunol. 2014 Oct; 35(10):454-6. View abstract
  52. Late endosomal trafficking of alternative serotype adenovirus vaccine vectors augments antiviral innate immunity. J Virol. 2014 Sep; 88(18):10354-63. View abstract
  53. Diverse intracellular pathogens activate type III interferon expression from peroxisomes. Nat Immunol. 2014 Aug; 15(8):717-26. View abstract
  54. Endosomes as platforms for NOD-like receptor signaling. . 2014 May 14; 15(5):523-5. View abstract
  55. A cross-disciplinary perspective on the innate immune responses to bacterial lipopolysaccharide. Mol Cell. 2014 Apr 24; 54(2):212-23. View abstract
  56. A bicistronic MAVS transcript highlights a class of truncated variants in antiviral immunity. Cell. 2014 Feb 13; 156(4):800-11. View abstract
  57. A promiscuous lipid-binding protein diversifies the subcellular sites of toll-like receptor signal transduction. Cell. 2014 Feb 13; 156(4):705-16. View abstract
  58. Finding a needle in a haystack of needles - a productive hunt for interferon stimulated genes with antiviral activity. Immunol Cell Biol. 2014 Mar; 92(3):205-7. View abstract
  59. Immunology. Sensing endotoxins from within. Science. 2013 Sep 13; 341(6151):1184-5. View abstract
  60. NLRP3 inflammasome activation: CD36 serves double duty. Nat Immunol. 2013 Aug; 14(8):772-4. View abstract
  61. Recognition for an innate explorer. Cell. 2013 Jul 18; 154(2):261-4. View abstract
  62. The unfolded protein response element IRE1a senses bacterial proteins invading the ER to activate RIG-I and innate immune signaling. . 2013 May 15; 13(5):558-569. View abstract
  63. Intracellular pathogen detection by RIG-I-like receptors. Adv Immunol. 2013; 117:99-125. View abstract
  64. Peroxisomes and the antiviral responses of mammalian cells. Subcell Biochem. 2013; 69:67-75. View abstract
  65. Signaling organelles of the innate immune system. Cell. 2012 Dec 07; 151(6):1168-78. View abstract
  66. Polymorphisms in toll-like receptor 4 underlie susceptibility to tumor induction by the mouse polyomavirus. J Virol. 2012 Nov; 86(21):11541-7. View abstract
  67. Defining the subcellular sites of innate immune signal transduction. Trends Immunol. 2012 Sep; 33(9):442-8. View abstract
  68. Phagosome as the organelle linking innate and adaptive immunity. Traffic. 2012 Aug; 13(8):1053-61. View abstract
  69. Phosphoinositide binding by the Toll adaptor dMyD88 controls antibacterial responses in Drosophila. Immunity. 2012 Apr 20; 36(4):612-22. View abstract
  70. CD14 controls the LPS-induced endocytosis of Toll-like receptor 4. Cell. 2011 Nov 11; 147(4):868-80. View abstract
  71. A phenotype of early infancy predicts reactivity of the amygdala in male adults. Mol Psychiatry. 2012 Oct; 17(10):1042-50. View abstract
  72. The IAP-antagonist ARTS initiates caspase activation upstream of cytochrome C and SMAC/Diablo. Cell Death Differ. 2012 Feb; 19(2):356-68. View abstract
  73. MyD88-dependent TLR1/2 signals educate dendritic cells with gut-specific imprinting properties. J Immunol. 2011 Jul 01; 187(1):141-50. View abstract
  74. Deciphering the function of nucleic acid sensing TLRs one regulatory step at a time. Front Biosci (Landmark Ed). 2011 Jun 01; 16:2060-8. View abstract
  75. Regulation of lipopolysaccharide-induced translation of tumor necrosis factor-alpha by the toll-like receptor 4 adaptor protein TRAM. J Innate Immun. 2011; 3(5):437-46. View abstract
  76. Interferon ß is associated with type 1 interferon-inducible gene expression in dermatomyositis. Ann Rheum Dis. 2011 May; 70(5):831-6. View abstract
  77. Recycling endosomes and TLR signaling--the Rab11 GTPase leads the way. Immunity. 2010 Oct 29; 33(4):578-80. View abstract
  78. Peroxisomes are signaling platforms for antiviral innate immunity. Cell. 2010 May 14; 141(4):668-81. View abstract
  79. "Complementing" toll signaling. Sci Signal. 2010 May 04; 3(120):pe15. View abstract
  80. Selective modulation of TLR4-activated inflammatory responses by altered iron homeostasis in mice. J Clin Invest. 2009 Nov; 119(11):3322-8. View abstract
  81. A cell biological view of Toll-like receptor function: regulation through compartmentalization. Nat Rev Immunol. 2009 Aug; 9(8):535-42. View abstract
  82. TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta. Nat Immunol. 2008 Apr; 9(4):361-8. View abstract
  83. Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling. Cell. 2006 Jun 02; 125(5):943-55. View abstract
  84. Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA. Nat Immunol. 2006 Jan; 7(1):49-56. View abstract
  85. Association of selected phenotypic markers of lymphocyte activation and differentiation with perinatal human immunodeficiency virus transmission and infant infection. Clin Diagn Lab Immunol. 2005 May; 12(5):622-31. View abstract
  86. Serum neopterin, an immune activation marker, independently predicts disease progression in advanced HIV-1 infection. Clin Infect Dis. 2005 Mar 15; 40(6):853-8. View abstract
  87. Analysis of Rab1 recruitment to vacuoles containing Legionella pneumophila. Methods Enzymol. 2005; 403:71-81. View abstract
  88. A C-terminal translocation signal required for Dot/Icm-dependent delivery of the Legionella RalF protein to host cells. Proc Natl Acad Sci U S A. 2005 Jan 18; 102(3):826-31. View abstract
  89. Immunophenotypic markers and antiretroviral therapy (IMART): T cell activation and maturation help predict treatment response. J Infect Dis. 2004 May 15; 189(10):1811-20. View abstract
  90. Legionella subvert the functions of Rab1 and Sec22b to create a replicative organelle. J Exp Med. 2004 May 03; 199(9):1201-11. View abstract
  91. Microtubule motors control membrane dynamics of Salmonella-containing vacuoles. J Cell Sci. 2004 Mar 01; 117(Pt 7):1033-45. View abstract
  92. Can immune markers predict subsequent discordance between immunologic and virologic responses to antiretroviral therapy? Adult AIDS Clinical Trials Group. Clin Infect Dis. 2003 Aug 15; 37(4):551-8. View abstract
  93. Cellular and Molecular Aspects of Legionella pneumophila transport to the endoplasmic reticulum. 2003. View abstract
  94. Legionella phagosomes intercept vesicular traffic from endoplasmic reticulum exit sites. Nat Cell Biol. 2002 Dec; 4(12):945-54. View abstract
  95. A bacterial guanine nucleotide exchange factor activates ARF on Legionella phagosomes. Science. 2002 Jan 25; 295(5555):679-82. View abstract
  96. Further evidence of association between behavioral inhibition and social anxiety in children. Am J Psychiatry. 2001 Oct; 158(10):1673-9. View abstract
  97. Efficacy of a mixed amphetamine salts compound in adults with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 2001 Aug; 58(8):775-82. View abstract
  98. Biological constraint, cultural variety, and psychological structures. Ann N Y Acad Sci. 2001 May; 935:177-90. View abstract
  99. Genetic association analysis of behavioral inhibition using candidate loci from mouse models. Am J Med Genet. 2001 Apr 08; 105(3):226-35. View abstract
  100. Impact of tic disorders on ADHD outcome across the life cycle: findings from a large group of adults with and without ADHD. Am J Psychiatry. 2001 Apr; 158(4):611-7. View abstract
  101. A controlled study of behavioral inhibition in children of parents with panic disorder and depression. Am J Psychiatry. 2000 Dec; 157(12):2002-10. View abstract
  102. Identification of Icm protein complexes that play distinct roles in the biogenesis of an organelle permissive for Legionella pneumophila intracellular growth. Mol Microbiol. 2000 Nov; 38(4):719-36. View abstract
  103. Adolescent social anxiety as an outcome of inhibited temperament in childhood. J Am Acad Child Adolesc Psychiatry. 1999 Aug; 38(8):1008-15. View abstract
  104. Startle potentiation by threat of aversive stimuli and darkness in adolescents: a multi-site study. Int J Psychophysiol. 1999 Apr; 32(1):63-73. View abstract
  105. Safety of autologous, ex vivo-expanded human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte infusion in HIV-infected patients. Blood. 1997 Sep 15; 90(6):2196-206. View abstract
  106. Influences of gender and social class on adolescents' perceptions of health. Arch Pediatr Adolesc Med. 1997 Sep; 151(9):899-904. View abstract
  107. Daylength during pregnancy and shyness in children: results from northern and southern hemispheres. Dev Psychobiol. 1997 Sep; 31(2):107-14. View abstract
  108. An approach to the validation of markers for use in AIDS clinical trials. Clin Infect Dis. 1997 May; 24(5):764-74. View abstract
  109. Three-color supplement to the NIAID DAIDS guideline for flow cytometric immunophenotyping. Cytometry. 1996 Sep 15; 26(3):227-30. View abstract
  110. A randomized, placebo-controlled study of the immunogenicity of human immunodeficiency virus (HIV) rgp160 vaccine in HIV-infected subjects with > or = 400/mm3 CD4 T lymphocytes (AIDS Clinical Trials Group Protocol 137). J Infect Dis. 1996 Jun; 173(6):1336-46. View abstract
  111. Standardization of absolute CD4+ lymphocyte counts across laboratories: an evaluation of the Ortho CytoronAbsolute flow cytometry system on normal donors. Cytometry. 1995 Sep 15; 22(3):200-10. View abstract
  112. Interlaboratory variability of CD8 subset measurements by flow cytometry and its applications to multicenter clinical trials. NAID/NICHD Women and Infants Transmission Study Group. Clin Diagn Lab Immunol. 1995 Jul; 2(4):462-8. View abstract
  113. A 3-year follow-up of children with and without behavioral inhibition. J Am Acad Child Adolesc Psychiatry. 1993 Jul; 32(4):814-21. View abstract
  114. Behavioral inhibition in childhood: a risk factor for anxiety disorders. Harv Rev Psychiatry. 1993 May-Jun; 1(1):2-16. View abstract
  115. NIAID Division of AIDS flow cytometry quality assessment program. Ann N Y Acad Sci. 1993 Mar 20; 677:50-2. View abstract
  116. Assessment of the effects of instrumentation, monoclonal antibody, and fluorochrome on flow cytometric immunophenotyping: a report based on 2 years of the NIAID DAIDS flow cytometry quality assessment program. Clin Immunol Immunopathol. 1993 Feb; 66(2):150-62. View abstract
  117. Comorbidity of parental anxiety disorders as risk for childhood-onset anxiety in inhibited children. Am J Psychiatry. 1992 Apr; 149(4):475-81. View abstract
  118. Stable behavioral inhibition and its association with anxiety disorder. J Am Acad Child Adolesc Psychiatry. 1992 Jan; 31(1):103-11. View abstract
  119. Cloning and expression of the human substance K receptor and analysis of its role in mitogenesis. Cell Growth Differ. 1991 Jan; 2(1):15-22. View abstract
  120. Further evidence of an association between behavioral inhibition and anxiety disorders: results from a family study of children from a non-clinical sample. J Psychiatr Res. 1991; 25(1-2):49-65. View abstract
  121. Depression and allergies: survey of a nonclinical population. Psychother Psychosom. 1991; 55(1):24-31. View abstract
  122. Is allergic rhinitis more frequent in young adults with extreme shyness? A preliminary survey. Psychosom Med. 1990 Sep-Oct; 52(5):517-25. View abstract
  123. Expression and function of gamma delta- and alpha beta-T cell receptor heterodimers on human somatic T cell hybrids. J Immunol. 1990 May 15; 144(10):3677-83. View abstract
  124. Psychiatric correlates of behavioral inhibition in young children of parents with and without psychiatric disorders. Arch Gen Psychiatry. 1990 Jan; 47(1):21-6. View abstract
  125. Behavioral inhibition in children of parents with panic disorder and agoraphobia. A controlled study. Arch Gen Psychiatry. 1988 May; 45(5):463-70. View abstract
  126. In vivo activity of affinity-purified helper factor from antigen-specific helper clone. J Immunol. 1985 Mar; 134(3):1717-22. View abstract
  127. In vitro selection of murine antigen-specific T-lymphocytes. I. Description of selection procedure. J Immunol Methods. 1981; 42(3):291-304. View abstract
  128. Antigen-induced proliferation of murine T-lymphocytes in vitro. II. The effect of different macrophage populations on the antigen-induced proliferative response. J Immunol Methods. 1981; 41(3):321-31. View abstract
  129. Antigen-induced proliferation of murine T-lymphocytes in vitro. I. Characterization of the lymphocyte culture system. J Immunol Methods. 1980; 37(1):15-27. View abstract