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Jonathan  Kagan, PhD

Jonathan Kagan
Kagan Laboratory
Medicine Research
Gastroenterology, Hepatology and Nutrition Research
Hospital Title:
Staff Scientist
Academic Title:
Associate Professor, Harvard Medical School
Research Focus Area:
Signal transduction pathways of the immune system
Contact Via Email
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Research Overview

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. 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

About Jonathan Kagan

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.


Publications powered by Harvard Catalyst Profiles
  1. Kagan JC. Editorial overview: Emerging concepts in host-virus interactions. Curr Opin Microbiol. 2016 Aug; 32:xii-xiii.
  2. Akula MK, Shi M, Jiang Z, Foster CE, Miao D, Li AS, Zhang X, Gavin RM, Forde SD, Germain G, Carpenter S, Rosadini CV, Gritsman K, Chae JJ, Hampton R, Silverman N, Gravallese EM, Kagan JC, Fitzgerald KA, Kastner DL, Golenbock DT, Bergo MO, Wang D. Control of the innate immune response by the mevalonate pathway. Nat Immunol. 2016 Aug; 17(8):922-9.
  3. Magalhães AC, Ferreira AR, Gomes S, Vieira M, Gouveia A, Valença I, Islinger M, Nascimento R, Schrader M, Kagan JC, Ribeiro D. Peroxisomes are platforms for cytomegalovirus' evasion from the cellular immune response. Sci Rep. 2016; 6:26028.
  4. Zanoni I, Tan Y, Di Gioia M, Broggi A, Ruan J, Shi J, Donado CA, Shao F, Wu H, Springstead JR, Kagan JC. An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells. Science. 2016 Jun 3; 352(6290):1232-6.
  5. Ferreira AR, Magalhães AC, Camões F, Gouveia A, Vieira M, Kagan JC, Ribeiro D. Hepatitis C virus NS3-4A inhibits the peroxisomal MAVS-dependent antiviral signalling response. J Cell Mol Med. 2016 Apr; 20(4):750-7.
  6. Rosadini CV, Zanoni I, Odendall C, Green ER, Paczosa MK, Philip NH, Brodsky IE, Mecsas J, Kagan JC. A Single Bacterial Immune Evasion Strategy Dismantles Both MyD88 and TRIF Signaling Pathways Downstream of TLR4. Cell Host Microbe. 2015 Dec 9; 18(6):682-93.
  7. Tan Y, Zanoni I, Cullen TW, Goodman AL, Kagan JC. 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.
  8. Chow J, Franz KM, Kagan JC. PRRs are watching you: Localization of innate sensing and signaling regulators. Virology. 2015 May; 479-480:104-9.
  9. Odendall C, Kagan JC. The unique regulation and functions of type III interferons in antiviral immunity. Curr Opin Virol. 2015 Jun; 12:47-52.
  10. Rosadini CV, Kagan JC. Microbial strategies for antagonizing Toll-like-receptor signal transduction. Curr Opin Immunol. 2015 Feb; 32:61-70.
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  12. Brubaker SW, Bonham KS, Zanoni I, Kagan JC. Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol. 2015; 33:257-90.
  13. Gwadz M, Cleland CM, Belkin M, Ritchie A, Leonard N, Riedel M, Banfield A, Colon P, Elharrar V, Kagan J, Mildvan D. 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.
  14. Kagan JC, Barton GM. Emerging principles governing signal transduction by pattern-recognition receptors. Cold Spring Harb Perspect Biol. 2015 Mar; 7(3):a016253.
  15. Kagan JC, Magupalli VG, Wu H. SMOCs: supramolecular organizing centres that control innate immunity. Nat Rev Immunol. 2014 Dec; 14(12):821-6.
  16. Kagan JC. Common mechanisms activate plant guard receptors and TLR4. Trends Immunol. 2014 Oct; 35(10):454-6.
  17. Teigler JE, Kagan JC, Barouch DH. Late endosomal trafficking of alternative serotype adenovirus vaccine vectors augments antiviral innate immunity. J Virol. 2014 Sep; 88(18):10354-63.
  18. Odendall C, Dixit E, Stavru F, Bierne H, Franz KM, Durbin AF, Boulant S, Gehrke L, Cossart P, Kagan JC. Diverse intracellular pathogens activate type III interferon expression from peroxisomes. Nat Immunol. 2014 Aug; 15(8):717-26.
  19. Bonham KS, Kagan JC. Endosomes as platforms for NOD-like receptor signaling. Cell Host Microbe. 2014 May 14; 15(5):523-5.
  20. Tan Y, Kagan JC. A cross-disciplinary perspective on the innate immune responses to bacterial lipopolysaccharide. Mol Cell. 2014 Apr 24; 54(2):212-23.
  21. Brubaker SW, Gauthier AE, Mills EW, Ingolia NT, Kagan JC. A bicistronic MAVS transcript highlights a class of truncated variants in antiviral immunity. Cell. 2014 Feb 13; 156(4):800-11.
  22. Bonham KS, Orzalli MH, Hayashi K, Wolf AI, Glanemann C, Weninger W, Iwasaki A, Knipe DM, Kagan JC. A promiscuous lipid-binding protein diversifies the subcellular sites of toll-like receptor signal transduction. Cell. 2014 Feb 13; 156(4):705-16.
  23. Franz KM, Kagan JC. 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.
  24. Kagan JC. Immunology. Sensing endotoxins from within. Science. 2013 Sep 13; 341(6151):1184-5.
  25. Kagan JC, Horng T. NLRP3 inflammasome activation: CD36 serves double duty. Nat Immunol. 2013 Aug; 14(8):772-4.
  26. Kagan JC. Recognition for an innate explorer. Cell. 2013 Jul 18; 154(2):261-4.
  27. Cho JA, Lee AH, Platzer B, Cross BC, Gardner BM, De Luca H, Luong P, Harding HP, Glimcher LH, Walter P, Fiebiger E, Ron D, Kagan JC, Lencer WI. The unfolded protein response element IRE1a senses bacterial proteins invading the ER to activate RIG-I and innate immune signaling. Cell Host Microbe. 2013 May 15; 13(5):558-69.
  28. Dixit E, Kagan JC. Intracellular pathogen detection by RIG-I-like receptors. Adv Immunol. 2013; 117:99-125.
  29. Odendall C, Kagan JC. Peroxisomes and the antiviral responses of mammalian cells. Subcell Biochem. 2013; 69:67-75.
  30. Kagan JC. Signaling organelles of the innate immune system. Cell. 2012 Dec 7; 151(6):1168-78.
  31. Velupillai P, Sung CK, Andrews E, Moran J, Beier D, Kagan J, Benjamin T. Polymorphisms in toll-like receptor 4 underlie susceptibility to tumor induction by the mouse polyomavirus. J Virol. 2012 Nov; 86(21):11541-7.
  32. Kagan JC. Defining the subcellular sites of innate immune signal transduction. Trends Immunol. 2012 Sep; 33(9):442-8.
  33. Kagan JC, Iwasaki A. Phagosome as the organelle linking innate and adaptive immunity. Traffic. 2012 Aug; 13(8):1053-61.
  34. Marek LR, Kagan JC. Phosphoinositide binding by the Toll adaptor dMyD88 controls antibacterial responses in Drosophila. Immunity. 2012 Apr 20; 36(4):612-22.
  35. Zanoni I, Ostuni R, Marek LR, Barresi S, Barbalat R, Barton GM, Granucci F, Kagan JC. CD14 controls the LPS-induced endocytosis of Toll-like receptor 4. Cell. 2011 Nov 11; 147(4):868-80.
  36. Schwartz CE, Kunwar PS, Greve DN, Kagan J, Snidman NC, Bloch RB. A phenotype of early infancy predicts reactivity of the amygdala in male adults. Mol Psychiatry. 2012 Oct; 17(10):1042-50.
  37. Wang S, Villablanca EJ, De Calisto J, Gomes DC, Nguyen DD, Mizoguchi E, Kagan JC, Reinecker HC, Hacohen N, Nagler C, Xavier RJ, Rossi-Bergmann B, Chen YB, Blomhoff R, Snapper SB, Mora JR. MyD88-dependent TLR1/2 signals educate dendritic cells with gut-specific imprinting properties. J Immunol. 2011 Jul 1; 187(1):141-50.
  38. Marek LR, Kagan JC. Deciphering the function of nucleic acid sensing TLRs one regulatory step at a time. Front Biosci (Landmark Ed). 2011; 16:2060-8.
  39. Wang L, Trebicka E, Fu Y, Waggoner L, Akira S, Fitzgerald KA, Kagan JC, Cherayil BJ. 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.
  40. Liao AP, Salajegheh M, Nazareno R, Kagan JC, Jubin RG, Greenberg SA. Interferon ß is associated with type 1 interferon-inducible gene expression in dermatomyositis. Ann Rheum Dis. 2011 May; 70(5):831-6.
  41. Kagan JC. Recycling endosomes and TLR signaling--the Rab11 GTPase leads the way. Immunity. 2010 Oct 29; 33(4):578-80.
  42. Dixit E, Boulant S, Zhang Y, Lee AS, Odendall C, Shum B, Hacohen N, Chen ZJ, Whelan SP, Fransen M, Nibert ML, Superti-Furga G, Kagan JC. Peroxisomes are signaling platforms for antiviral innate immunity. Cell. 2010 May 14; 141(4):668-81.
  43. Kagan JC. "Complementing" toll signaling. Sci Signal. 2010; 3(120):pe15.
  44. Wang L, Harrington L, Trebicka E, Shi HN, Kagan JC, Hong CC, Lin HY, Babitt JL, Cherayil BJ. Selective modulation of TLR4-activated inflammatory responses by altered iron homeostasis in mice. J Clin Invest. 2009 Nov; 119(11):3322-8.
  45. Barton GM, Kagan JC. A cell biological view of Toll-like receptor function: regulation through compartmentalization. Nat Rev Immunol. 2009 Aug; 9(8):535-42.
  46. Kagan JC, Su T, Horng T, Chow A, Akira S, Medzhitov R. TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta. Nat Immunol. 2008 Apr; 9(4):361-8.
  47. Kagan JC, Medzhitov R. Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling. Cell. 2006 Jun 2; 125(5):943-55.
  48. Barton GM, Kagan JC, Medzhitov R. 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.
  49. Lambert JS, Moye J, Plaeger SF, Stiehm ER, Bethel J, Mofenson LM, Mathieson B, Kagan J, Rosenblatt H, Paxton H, Suter H, Landay A. 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.
  50. Mildvan D, Spritzler J, Grossberg SE, Fahey JL, Johnston DM, Schock BR, Kagan J. 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.
  51. Kagan JC, Murata T, Roy CR. Analysis of Rab1 recruitment to vacuoles containing Legionella pneumophila. Methods Enzymol. 2005; 403:71-81.
  52. Nagai H, Cambronne ED, Kagan JC, Amor JC, Kahn RA, Roy CR. 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.
  53. Mildvan D, Bosch RJ, Kim RS, Spritzler J, Haas DW, Kuritzkes D, Kagan J, Nokta M, DeGruttola V, Moreno M, Landay A. 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.
  54. Kagan JC, Stein MP, Pypaert M, Roy CR. Legionella subvert the functions of Rab1 and Sec22b to create a replicative organelle. J Exp Med. 2004 May 3; 199(9):1201-11.
  55. Guignot J, Caron E, Beuzón C, Bucci C, Kagan J, Roy C, Holden DW. Microtubule motors control membrane dynamics of Salmonella-containing vacuoles. J Cell Sci. 2004 Mar 1; 117(Pt 7):1033-45.
  56. Spritzler J, Mildvan D, Russo A, Asthana D, Livnat D, Schock B, Kagan J, Landay A, Haas DW. 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.
  57. Jonathan C. Kagan. Cellular and Molecular Aspects of Legionella pneumophila transport to the endoplasmic reticulum. 2003.
  58. Kagan JC, Roy CR. Legionella phagosomes intercept vesicular traffic from endoplasmic reticulum exit sites. Nat Cell Biol. 2002 Dec; 4(12):945-54.
  59. Nagai H, Kagan JC, Zhu X, Kahn RA, Roy CR. A bacterial guanine nucleotide exchange factor activates ARF on Legionella phagosomes. Science. 2002 Jan 25; 295(5555):679-82.
  60. Biederman J, Hirshfeld-Becker DR, Rosenbaum JF, Hérot C, Friedman D, Snidman N, Kagan J, Faraone SV. Further evidence of association between behavioral inhibition and social anxiety in children. Am J Psychiatry. 2001 Oct; 158(10):1673-9.
  61. Spencer T, Biederman J, Wilens T, Faraone S, Prince J, Gerard K, Doyle R, Parekh A, Kagan J, Bearman SK. Efficacy of a mixed amphetamine salts compound in adults with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 2001 Aug; 58(8):775-82.
  62. Smoller JW, Rosenbaum JF, Biederman J, Susswein LS, Kennedy J, Kagan J, Snidman N, Laird N, Tsuang MT, Faraone SV, Schwarz A, Slaugenhaupt SA. Genetic association analysis of behavioral inhibition using candidate loci from mouse models. Am J Med Genet. 2001 Apr 8; 105(3):226-35.
  63. Spencer TJ, Biederman J, Faraone S, Mick E, Coffey B, Geller D, Kagan J, Bearman SK, Wilens T. 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.
  64. Rosenbaum JF, Biederman J, Hirshfeld-Becker DR, Kagan J, Snidman N, Friedman D, Nineberg A, Gallery DJ, Faraone SV. A controlled study of behavioral inhibition in children of parents with panic disorder and depression. Am J Psychiatry. 2000 Dec; 157(12):2002-10.
  65. Coers J, Kagan JC, Matthews M, Nagai H, Zuckman DM, Roy CR. 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.
  66. Schwartz CE, Snidman N, Kagan J. Adolescent social anxiety as an outcome of inhibited temperament in childhood. J Am Acad Child Adolesc Psychiatry. 1999 Aug; 38(8):1008-15.
  67. Grillon C, Merikangas KR, Dierker L, Snidman N, Arriaga RI, Kagan J, Donzella B, Dikel T, Nelson C. Startle potentiation by threat of aversive stimuli and darkness in adolescents: a multi-site study. Int J Psychophysiol. 1999 Apr; 32(1):63-73.
  68. Lieberman J, Skolnik PR, Parkerson GR, Fabry JA, Landry B, Bethel J, Kagan J. 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.
  69. Goodman E, Amick BC, Rezendes MO, Tarlov AR, Rogers WH, Kagan J. Influences of gender and social class on adolescents' perceptions of health. Arch Pediatr Adolesc Med. 1997 Sep; 151(9):899-904.
  70. Gortmaker SL, Kagan J, Caspi A, Silva PA. Daylength during pregnancy and shyness in children: results from northern and southern hemispheres. Dev Psychobiol. 1997 Sep; 31(2):107-14.
  71. Mildvan D, Landay A, De Gruttola V, Machado SG, Kagan J. An approach to the validation of markers for use in AIDS clinical trials. Clin Infect Dis. 1997 May; 24(5):764-74.
  72. Nicholson J, Kidd P, Mandy F, Livnat D, Kagan J. Three-color supplement to the NIAID DAIDS guideline for flow cytometric immunophenotyping. Cytometry. 1996 Sep 15; 26(3):227-30.
  73. Valentine FT, Kundu S, Haslett PA, Katzenstein D, Beckett L, Spino C, Borucki M, Vasquez M, Smith G, Korvick J, Kagan J, Merigan TC. A randomized, placebo-controlled study of the immunogenicity of human immunodeficiency virus (HIV) rgp160 vaccine in HIV-infected subjects with &gt or = 400/mm3 CD4 T lymphocytes (AIDS Clinical Trials Group Protocol 137). J Infect Dis. 1996 Jun; 173(6):1336-46.
  74. Connelly MC, Knight M, Giorgi JV, Kagan J, Landay AL, Parker JW, Page E, Spino C, Wilkening C, Mercolino TJ. 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.
  75. Landay AL, Brambilla D, Pitt J, Hillyer G, Golenbock D, Moye J, Landesman S, Kagan J. 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.
  76. Biederman J, Rosenbaum JF, Bolduc-Murphy EA, Faraone SV, Chaloff J, Hirshfeld DR, Kagan J. A 3-year follow-up of children with and without behavioral inhibition. J Am Acad Child Adolesc Psychiatry. 1993 Jul; 32(4):814-21.
  77. Rosenbaum JF, Biederman J, Bolduc-Murphy EA, Faraone SV, Chaloff J, Hirshfeld DR, Kagan J. Behavioral inhibition in childhood: a risk factor for anxiety disorders. Harv Rev Psychiatry. 1993 May-Jun; 1(1):2-16.
  78. Gelman R, Cheng SC, Kidd P, Waxdal M, Kagan J. 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.
  79. Rosenbaum JF, Biederman J, Bolduc EA, Hirshfeld DR, Faraone SV, Kagan J. Comorbidity of parental anxiety disorders as risk for childhood-onset anxiety in inhibited children. Am J Psychiatry. 1992 Apr; 149(4):475-81.
  80. Hirshfeld DR, Rosenbaum JF, Biederman J, Bolduc EA, Faraone SV, Snidman N, Reznick JS, Kagan J. Stable behavioral inhibition and its association with anxiety disorder. J Am Acad Child Adolesc Psychiatry. 1992 Jan; 31(1):103-11.
  81. Kris RM, South V, Saltzman A, Felder S, Ricca GA, Jaye M, Huebner K, Kagan J, Croce CM, Schlessinger J. 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.
  82. Rosenbaum JF, Biederman J, Hirshfeld DR, Bolduc EA, Faraone SV, Kagan J, Snidman N, Reznick JS. 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.
  83. Biederman J, Rosenbaum JF, Hirshfeld DR, Faraone SV, Bolduc EA, Gersten M, Meminger SR, Kagan J, Snidman N, Reznick JS. Psychiatric correlates of behavioral inhibition in young children of parents with and without psychiatric disorders. Arch Gen Psychiatry. 1990 Jan; 47(1):21-6.
  84. Rosenbaum JF, Biederman J, Gersten M, Hirshfeld DR, Meminger SR, Herman JB, Kagan J, Reznick JS, Snidman N. Behavioral inhibition in children of parents with panic disorder and agoraphobia. A controlled study. Arch Gen Psychiatry. 1988 May; 45(5):463-70.
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