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Related Research Units

Gastroenterology, Hepatology and Nutrition Research

Research Overview

Our goal is to understand the principles of how inflammation drives memory formation in human barrier tissues, in order to program and re-program them in disease. We are developing a training environment where we apply emerging techniques to answer fundamental questions of biological and clinical relevance in barrier tissue biology.

Conceptually, for a barrier tissue to effectively learn from previous immunological experiences, it can sense, adapt, and store this information (i.e. memory) in readily accessible permanent resident cell types. We are interested in exploring how memories of previous immune events (i.e. inflammatory memory) enables barrier tissues (airway, intestine, and skin) to recall diverse environmental exposures, informing future responses. We are particularly interested in further understanding our discovery that epithelial stem cells, amongst other parenchymal, stromal, neuronal, and immune cell subsets, can form inflammatory memory, raising the possibility of distributed memory formation.

Technically, we utilize single-cell RNA-sequencing (scRNA-seq), computational methods, organoid models, epigenetic profiling, flow cytometry, and microscopy applied to human health and disease. We then build testable models to explore with humans (organoids, treatment response vs. failure) or with mice (genetics, optogenetics, cellular immunology), towards the aim of improving disease understanding and treatment.

Our approach is to integrate immunological insights with innovative technologies, experimentation, and computational methods. Current projects in the lab focus on:

  1. Understanding human inflammatory diseases at single-cell resolution in barrier tissues (allergic inflammation, Crohn’s, colitis, psoriasis, eczema),
  2. Defining the mechanisms of inflammatory adaptation and memory by epithelial stem cells, and
  3. Building a framework for how inflammation changes the states of epithelial, stromal and immune cells to reshape their interactions.

If you have any idea that fits within these broad interests, please reach out!

Research Background

Jose grew up in a Spanish household within the Boston area, attending high school in Framingham, MA, college at Tufts University, and graduate studies in the Harvard Immunology program. During his undergraduate, Jose worked in human immunology labs at Biogen Idec, University College London, and Boston Children's Hospital, where he focused on monogenic immune deficiencies. For his PhD work, Jose trained with Uli von Andrian, studying how the nervous system and the immune system function together as the principal sensory interfaces between the internal and external environments.

Seeking experimental approaches to return to the human system, he decided to gain first-hand experience in the nascent field of single-cell genomics to be able to work across multiple cell types in barrier tissues. As a Damon Runyon Postdoctoral Fellow in the Laboratory of Alex K. Shalek at MIT, the Broad, and the Ragon Institute, he began charting maps of human gut and airway, and discovered how human stem cells can be shaped by, and remember, inflammation. Jose started his group in 2019 at Boston Children's Hospital. He continues to be supported by a great team of undergraduate students, graduate students, technicians and colleagues, and looks forward to his lab integrating with the BCH community.

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. Type III interferons induce pyroptosis in gut epithelial cells and impair mucosal repair. Cell. 2024 Dec 26; 187(26):7533-7550.e23. View Abstract
  3. Deconstructing inflammatory memory across tissue set points using cell circuit motifs. J Allergy Clin Immunol. 2024 Nov; 154(5):1095-1105. View Abstract
  4. The choroid plexus synergizes with immune cells during neuroinflammation. Cell. 2024 Sep 05; 187(18):4946-4963.e17. View Abstract
  5. Distinct olfactory mucosal macrophage populations mediate neuronal maintenance and pathogen defense. Mucosal Immunol. 2024 10; 17(5):1102-1113. View Abstract
  6. Primary nasal influenza infection rewires tissue-scale memory response dynamics. Immunity. 2024 08 13; 57(8):1955-1974.e8. View Abstract
  7. 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
  8. Primary nasal viral infection rewires the tissue-scale memory response. bioRxiv. 2024 Mar 18. View Abstract
  9. 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
  10. A collaboration between immune cells and the choroid plexus epithelium in brain inflammation. bioRxiv. 2023 Aug 08. View Abstract
  11. Leveraging polygenic enrichments of gene features to predict genes underlying complex traits and diseases. Nat Genet. 2023 08; 55(8):1267-1276. View Abstract
  12. Respiratory epithelial cell types, states and fates in the era of single-cell RNA-sequencing. Biochem J. 2023 07 12; 480(13):921-939. View Abstract
  13. A Roadmap for the Human Gut Cell Atlas. Nat Rev Gastroenterol Hepatol. 2023 09; 20(9):597-614. View Abstract
  14. 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
  15. Are we there yet? An immune field trip through human embryonic development. Immunity. 2022 07 12; 55(7):1153-1155. View Abstract
  16. Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control. Immunity. 2022 05 10; 55(5):827-846.e10. View Abstract
  17. Role of Respiratory Epithelial Cells in Allergic Diseases. Cells. 2022 04 20; 11(9). View Abstract
  18. Rapid and sustained effect of dupilumab on clinical and mechanistic outcomes in aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 2022 08; 150(2):415-424. View Abstract
  19. Screening for modulators of the cellular composition of gut epithelia via organoid models of intestinal stem cell differentiation. Nat Biomed Eng. 2022 04; 6(4):476-494. View Abstract
  20. Erratum: Prior upregulation of interferon pathways in the nasopharynx impacts viral shedding following live attenuated influenza vaccine challenge in children. Cell Rep Med. 2022 Feb 15; 3(2):100516. View Abstract
  21. Robust differentiation of human enteroendocrine cells from intestinal stem cells. Nat Commun. 2022 01 11; 13(1):261. View Abstract
  22. Prior upregulation of interferon pathways in the nasopharynx impacts viral shedding following live attenuated influenza vaccine challenge in children. Cell Rep Med. 2021 12 21; 2(12):100465. View Abstract
  23. 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
  24. Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19. Cell. 2021 09 02; 184(18):4713-4733.e22. View Abstract
  25. Mepolizumab targets multiple immune cells in aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 2021 08; 148(2):574-584. View Abstract
  26. Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells. J Exp Med. 2021 04 05; 218(4). View Abstract
  27. Human airway mast cells proliferate and acquire distinct inflammation-driven phenotypes during type 2 inflammation. Sci Immunol. 2021 02 26; 6(56). View Abstract
  28. Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19. bioRxiv. 2021 Feb 20. View Abstract
  29. Spatiotemporal single-cell profiling reveals that invasive and tissue-resident memory donor CD8+ T cells drive gastrointestinal acute graft-versus-host disease. Sci Transl Med. 2021 01 13; 13(576). View Abstract
  30. Lymph nodes are innervated by a unique population of sensory neurons with immunomodulatory potential. Cell. 2021 01 21; 184(2):441-459.e25. View Abstract
  31. Second-Strand Synthesis-Based Massively Parallel scRNA-Seq Reveals Cellular States and Molecular Features of Human Inflammatory Skin Pathologies. Immunity. 2020 10 13; 53(4):878-894.e7. View Abstract
  32. 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
  33. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell. 2020 05 28; 181(5):1016-1035.e19. View Abstract
  34. Integrated single-cell analysis of multicellular immune dynamics during hyperacute HIV-1 infection. Nat Med. 2020 04; 26(4):511-518. View Abstract
  35. IL-5Ra marks nasal polyp IgG4- and IgE-expressing cells in aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 2020 06; 145(6):1574-1584. View Abstract
  36. Distribution and storage of inflammatory memory in barrier tissues. Nat Rev Immunol. 2020 05; 20(5):308-320. View Abstract
  37. Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis. Cell. 2019 07 25; 178(3):714-730.e22. View Abstract
  38. Single-Cell Analysis of the Liver Epithelium Reveals Dynamic Heterogeneity and an Essential Role for YAP in Homeostasis and Regeneration. Cell Stem Cell. 2019 07 03; 25(1):23-38.e8. View Abstract
  39. T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation. Cell. 2018 11 15; 175(5):1307-1320.e22. View Abstract
  40. Allergic inflammatory memory in human respiratory epithelial progenitor cells. Nature. 2018 08; 560(7720):649-654. View Abstract
  41. Harnessing single-cell genomics to improve the physiological fidelity of organoid-derived cell types. BMC Biol. 2018 06 05; 16(1):62. View Abstract
  42. A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced Antiviral State in Dendritic Cells from HIV-1 Elite Controllers. Genome Biol. 2018 01 29; 19(1):10. View Abstract
  43. Correction: Novel in vitro booster vaccination to rapidly generate antigen-specific human monoclonal antibodies. J Exp Med. 2017 09 04; 214(9):2811. View Abstract
  44. Novel in vitro booster vaccination to rapidly generate antigen-specific human monoclonal antibodies. J Exp Med. 2017 Aug 07; 214(8):2471-2490. View Abstract
  45. The Whiteboard Revolution: Illuminating Science Communication in the Digital Age. Trends Immunol. 2016 Apr; 37(4):250-3. View Abstract
  46. The Regulation of Immunological Processes by Peripheral Neurons in Homeostasis and Disease. Trends Immunol. 2015 Oct; 36(10):578-604. View Abstract
  47. Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation. Nature. 2014 Jun 05; 510(7503):157-61. View Abstract
  48. Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS cells. Nature. 2012 Nov 29; 491(7426):769-73. View Abstract
  49. Cholesterol, Inflammasomes, and Atherogenesis. Curr Cardiovasc Risk Rep. 2012 Feb 01; 6(1):45-52. View Abstract
  50. Induced pluripotent stem cells: a novel frontier in the study of human primary immunodeficiencies. J Allergy Clin Immunol. 2011 Jun; 127(6):1400-7.e4. View Abstract

Contact Jose Ordovas-Montanes

Phone: 617-919-7692
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