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Research Overview

Dr. Horwitz is a pediatric emergency physician and mucosal immunologist. He studies viral respiratory illnesses in young children with the goal of developing mechanistically informed therapeutic strategies. Areas of particular interest include RSV-induced bronchiolitis and rhinovirus-induced asthma exacerbations. He co-directs a mucosal immunology research program focused on the regulation of inflammatory responses at mucosal surfaces including the respiratory and gastrointestinal tracts.

Research Background

Dr. Horwitz received an MD and PhD from Yale University. He completed residency training in Pediatrics and fellowship training in Pediatric Emergency Medicine at Boston Children’s Hospital. He was a fellow in Biology at MIT and established an independent research laboratory at the Brigham and Women’s Hospital and Harvard Medical School in 1998. Since 2020 Dr. Horwitz has co-directed a research laboratory in the Division of Gastroenterology, Hepatology, and Nutrition at Children’s Hospital, which focuses on mucosal immune responses.

Education

Medical School

Yale University School of Medicine
1991 New Haven CT

Internship

Boston Children's Hospital
1991 Boston MA

Residency

Boston Children's Hospital
1994 Boston MA

Fellowship

Boston Children's Hospital
1996 Boston MA

Publications

  1. Variants and vaccines impact nasal immunity over three waves of SARS-CoV-2. Nat Immunol. 2025 Feb; 26(2):294-307. View Abstract
  2. COVID-19 mRNA Vaccines Induce Robust Levels of IgG but Limited Amounts of IgA Within the Oronasopharynx of Young Children. J Infect Dis. 2024 Dec 16; 230(6):1390-1399. View Abstract
  3. Bacterial Sphingolipids Exacerbate Colitis by Inhibiting ILC3-derived IL-22 Production. Cell Mol Gastroenterol Hepatol. 2024; 18(2):101350. View Abstract
  4. An enhanced IL17 and muted type I interferon nasal epithelial cell state characterizes severe COVID-19 with fungal coinfection. Microbiol Spectr. 2024 Jun 04; 12(6):e0351623. View Abstract
  5. COVID-19 mRNA vaccines induce robust levels of IgG but limited amounts of IgA within the oronasopharynx of young children. medRxiv. 2024 Apr 16. View Abstract
  6. Humoral profiles of toddlers and young children following SARS-CoV-2 mRNA vaccination. Nat Commun. 2024 Jan 30; 15(1):905. View Abstract
  7. Enhanced production of eicosanoids in plasma and activation of DNA damage pathways in PBMCs are correlated with the severity of ancestral COVID-19 infection. medRxiv. 2023 Sep 15. View Abstract
  8. Humoral profiles of toddlers and young children following SARS-CoV-2 mRNA vaccination. Res Sq. 2023 Apr 06. View Abstract
  9. The IL-10 receptor inhibits cell extrinsic signals necessary for STAT1-dependent macrophage accumulation during colitis. Mucosal Immunol. 2023 06; 16(3):233-249. View Abstract
  10. Severe COVID-19 is associated with fungal colonization of the nasopharynx and potent induction of IL-17 responses in the nasal epithelium. medRxiv. 2022 Oct 26. View Abstract
  11. Monocytes transition to macrophages within the inflamed vasculature via monocyte CCR2 and endothelial TNFR2. J Exp Med. 2022 05 02; 219(5). View Abstract
  12. CCR2 promotes monocyte recruitment and intestinal inflammation in mice lacking the interleukin-10 receptor. Sci Rep. 2022 01 10; 12(1):452. View Abstract
  13. Variants in STXBP3 are Associated with Very Early Onset Inflammatory Bowel Disease, Bilateral Sensorineural Hearing Loss and Immune Dysregulation. J Crohns Colitis. 2021 Nov 08; 15(11):1908-1919. View Abstract
  14. Utilizing a reductionist model to study host-microbe interactions in intestinal inflammation. Microbiome. 2021 11 03; 9(1):215. View Abstract
  15. Increased ACE2 Levels and Mortality Risk of Patients With COVID-19 on Proton Pump Inhibitor Therapy. Am J Gastroenterol. 2021 08 01; 116(8):1638-1645. View Abstract
  16. Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19. Cell. 2021 09 02; 184(18):4713-4733.e22. View Abstract
  17. Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19. bioRxiv. 2021 Feb 20. View Abstract
  18. Characterizing T cell subsets in the nasal mucosa of children with acute respiratory symptoms. Pediatr Res. 2021 11; 90(5):1023-1030. View Abstract
  19. Single-Cell Analyses of Colon and Blood Reveal Distinct Immune Cell Signatures of Ulcerative Colitis and Crohn's Disease. Gastroenterology. 2020 08; 159(2):591-608.e10. View Abstract
  20. Effects of Colonization of Gnotobiotic Swiss Webster Mice with Helicobacter bilis. Comp Med. 2020 06 01; 70(3):216-232. View Abstract
  21. Generation of protective pneumococcal-specific nasal resident memory CD4+ T cells via parenteral immunization. Mucosal Immunol. 2020 01; 13(1):172-182. View Abstract
  22. Alpha kinase 1 controls intestinal inflammation by suppressing the IL-12/Th1 axis. Nat Commun. 2018 09 18; 9(1):3797. View Abstract
  23. WASP-mediated regulation of anti-inflammatory macrophages is IL-10 dependent and is critical for intestinal homeostasis. Nat Commun. 2018 05 03; 9(1):1779. View Abstract
  24. Macrophage dysfunction initiates colitis during weaning of infant mice lacking the interleukin-10 receptor. Elife. 2017 07 05; 6. View Abstract
  25. Inhibition of Inflammatory Gene Transcription by IL-10 Is Associated with Rapid Suppression of Lipopolysaccharide-Induced Enhancer Activation. J Immunol. 2017 04 01; 198(7):2906-2915. View Abstract
  26. Interleukin-22 drives nitric oxide-dependent DNA damage and dysplasia in a murine model of colitis-associated cancer. Mucosal Immunol. 2017 11; 10(6):1504-1517. View Abstract
  27. Interleukin 1ß Mediates Intestinal Inflammation in Mice and Patients With Interleukin 10 Receptor Deficiency. Gastroenterology. 2016 12; 151(6):1100-1104. View Abstract
  28. O-005 YI Microbiota Drives Inflammation by Altering Intestinal Lamina Propria Macrophage Phenotype in a Novel IL10R-Deficient Model of Very Early Onset IBD. Inflamm Bowel Dis. 2016 Mar; 22 Suppl 1:S2-3. View Abstract
  29. Fatal autoimmunity in mice reconstituted with human hematopoietic stem cells encoding defective FOXP3. Blood. 2015 Jun 18; 125(25):3886-95. View Abstract
  30. Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function. Immunity. 2014 May 15; 40(5):706-19. View Abstract
  31. Interleukin 10 receptor signaling: master regulator of intestinal mucosal homeostasis in mice and humans. Adv Immunol. 2014; 122:177-210. View Abstract
  32. Pathogenic intestinal bacteria enhance prostate cancer development via systemic activation of immune cells in mice. PLoS One. 2013; 8(8):e73933. View Abstract
  33. Endothelial TNF receptor 2 induces IRF1 transcription factor-dependent interferon-ß autocrine signaling to promote monocyte recruitment. Immunity. 2013 May 23; 38(5):1025-37. View Abstract
  34. Wiskott-Aldrich syndrome protein deficiency in innate immune cells leads to mucosal immune dysregulation and colitis in mice. Gastroenterology. 2012 Sep; 143(3):719-729.e2. View Abstract
  35. Nfkb1 inhibits LPS-induced IFN-ß and IL-12 p40 production in macrophages by distinct mechanisms. PLoS One. 2012; 7(3):e32811. View Abstract
  36. NF-?B1 inhibits TLR-induced IFN-ß production in macrophages through TPL-2-dependent ERK activation. J Immunol. 2011 Feb 15; 186(4):1989-96. View Abstract
  37. Helicobacter hepaticus infection in mice: models for understanding lower bowel inflammation and cancer. Mucosal Immunol. 2011 Jan; 4(1):22-30. View Abstract
  38. Unifying roles for regulatory T cells and inflammation in cancer. Int J Cancer. 2010 Apr 01; 126(7):1651-65. View Abstract
  39. Serum markers in acute appendicitis. J Surg Res. 2011 Jun 01; 168(1):70-5. View Abstract
  40. Discovery and validation of urine markers of acute pediatric appendicitis using high-accuracy mass spectrometry. Ann Emerg Med. 2010 Jan; 55(1):62-70.e4. View Abstract
  41. Cytotoxic-T-lymphocyte-associated antigen 4 blockade abrogates protection by regulatory T cells in a mouse model of microbially induced innate immune-driven colitis. Infect Immun. 2008 Dec; 76(12):5834-42. View Abstract
  42. Acute appendicitis is characterized by a uniform and highly selective pattern of inflammatory gene expression. Mucosal Immunol. 2008 Jul; 1(4):297-308. View Abstract
  43. c-Rel is essential for the development of innate and T cell-induced colitis. J Immunol. 2008 Jun 15; 180(12):8118-25. View Abstract
  44. NF-kappaB p50 and p65 subunits control intestinal homeostasis. Eur J Immunol. 2007 Sep; 37(9):2509-17. View Abstract
  45. Rapid reversal of interleukin-6-dependent epithelial invasion in a mouse model of microbially induced colon carcinoma. Carcinogenesis. 2007 Dec; 28(12):2614-23. View Abstract
  46. The straw that stirs the drink: insight into the pathogenesis of inflammatory bowel disease revealed through the study of microflora-induced inflammation in genetically modified mice. Inflamm Bowel Dis. 2007 Apr; 13(4):490-500. View Abstract
  47. Inhibition of Helicobacter hepaticus-induced colitis by IL-10 requires the p50/p105 subunit of NF-kappa B. J Immunol. 2006 Nov 15; 177(10):7332-9. View Abstract
  48. Innate immune inflammatory response against enteric bacteria Helicobacter hepaticus induces mammary adenocarcinoma in mice. Cancer Res. 2006 Aug 01; 66(15):7395-400. View Abstract
  49. Defective activation of ERK in macrophages lacking the p50/p105 subunit of NF-kappaB is responsible for elevated expression of IL-12 p40 observed after challenge with Helicobacter hepaticus. J Immunol. 2006 Jan 15; 176(2):1244-51. View Abstract
  50. Proinflammatory CD4+ CD45RB(hi) lymphocytes promote mammary and intestinal carcinogenesis in Apc(Min/+) mice. Cancer Res. 2006 Jan 01; 66(1):57-61. View Abstract
  51. NF-kappa B, an inhibitor of microflora-induced colitis. J Pediatr Gastroenterol Nutr. 2005 Apr; 40 Suppl 1:S22-3. View Abstract
  52. A role for NF-kappa B subunits p50 and p65 in the inhibition of lipopolysaccharide-induced shock. J Immunol. 2004 Nov 01; 173(9):5786-93. View Abstract
  53. Induction of activation-induced cytidine deaminase gene expression by IL-4 and CD40 ligation is dependent on STAT6 and NFkappaB. Int Immunol. 2004 Mar; 16(3):395-404. View Abstract
  54. Gastroenteritis in NF-kappaB-deficient mice is produced with wild-type Camplyobacter jejuni but not with C. jejuni lacking cytolethal distending toxin despite persistent colonization with both strains. Infect Immun. 2004 Feb; 72(2):1116-25. View Abstract
  55. Regulation of PD-1, PD-L1, and PD-L2 expression during normal and autoimmune responses. Eur J Immunol. 2003 Oct; 33(10):2706-16. View Abstract
  56. CD4(+)CD25(+) regulatory lymphocytes require interleukin 10 to interrupt colon carcinogenesis in mice. Cancer Res. 2003 Sep 15; 63(18):6042-50. View Abstract
  57. NF-kappa B is required within the innate immune system to inhibit microflora-induced colitis and expression of IL-12 p40. J Immunol. 2003 Aug 01; 171(3):1484-92. View Abstract
  58. CD4+ CD25+ regulatory T lymphocytes inhibit microbially induced colon cancer in Rag2-deficient mice. Am J Pathol. 2003 Feb; 162(2):691-702. View Abstract
  59. Targeted mutation of TNF receptor I rescues the RelA-deficient mouse and reveals a critical role for NF-kappa B in leukocyte recruitment. J Immunol. 2001 Aug 01; 167(3):1592-600. View Abstract
  60. Mechanisms of granulocytosis in the absence of CD18. Blood. 2001 Mar 15; 97(6):1578-83. View Abstract
  61. Typhlocolitis in NF-kappa B-deficient mice. J Immunol. 2001 Feb 01; 166(3):1443-7. View Abstract
  62. Nuclear factor kappa B is required for the development of marginal zone B lymphocytes. J Exp Med. 2000 Oct 16; 192(8):1175-82. View Abstract
  63. Effects of CD18 deficiency on the emigration of murine neutrophils during pneumonia. J Immunol. 1999 Jul 15; 163(2):995-9. View Abstract
  64. The p65 subunit of NF-kappa B is redundant with p50 during B cell proliferative responses, and is required for germline CH transcription and class switching to IgG3. J Immunol. 1999 Feb 15; 162(4):1941-6. View Abstract
  65. Failure of lymphopoiesis after adoptive transfer of NF-kappaB-deficient fetal liver cells. Immunity. 1997 Jun; 6(6):765-72. View Abstract
  66. Inverse relationship of peripheral thyrotropin-stimulating hormone levels to brain activity in mood disorders. Am J Psychiatry. 1997 Feb; 154(2):224-30. View Abstract
  67. Brain activity during transient sadness and happiness in healthy women. Am J Psychiatry. 1995 Mar; 152(3):341-51. View Abstract
  68. Regional brain activity when selecting a response despite interference: An H2 (15) O PET study of the stroop and an emotional stroop. Hum Brain Mapp. 1994; 1(3):194-209. View Abstract
  69. Bovine papillomavirus E2 gene regulates expression of the viral E5 transforming gene. J Virol. 1988 Oct; 62(10):3608-13. View Abstract

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