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Cathryn R. Nagler

Professor
cnagler@bsd.uchicago.edu
Research Summary
The Nagler Lab studies the mechanisms governing tolerance to dietary antigens. They were one of the first to identify a link between resident intestinal bacteria and the regulation of mucosal immunity. During the last fifteen years, their work has focused on examining how commensal bacteria regulate susceptibility to allergic responses to food. They have proposed that the striking generational increase in food allergies can be explained, in part, by alterations in the composition and function of the commensal microbiome. In support of this hypothesis, Nagler Lab described a role for a particular population of mucosa-associated commensal bacteria in protection from allergic sensitization in mice. Initial translational studies showed that the composition of the fecal microbiota is altered in infants with cow’s milk allergy. To understand how the microbiota regulates allergic disease in humans they have colonized germ free mice with human bacteria from the feces of healthy or cow’s milk allergic (CMA) infants. The group discovered that mice colonized with CMA infants’ microbiota exhibited an anaphylactic response to the cow’s milk allergen b-lactoglobulin, while mice colonized with healthy infants’ microbiota were protected against an allergic response. They defined a microbiota signature that distinguishes the CMA and healthy populations in both the human donors and the colonized mice. Analysis of gene expression in ileal intestinal epithelial cells of colonized mice identified a significant correlation between the genes associated with allergy protection and taxa from the Lachnospiraceae family, supporting a causal role for specific bacterial species in protection against food allergy. These robust, pre-clinical, gnotobiotic models are an ideal system to identify key host-microbial interactions that contribute to allergic sensitization to food. With support from the Polsky Center for Entrepreneurship and Innovation, Nagler Lab has created a start-up company, ClostraBio, to develop novel microbiome-modulating therapeutics to prevent or treat food allergy.
Keywords
Microbiome, Food Allergy, Tolerance
Education
  • Massachusetts Institute of Technology, Cambridge, MA, Postdoctoral Fellowship Immunology 07/1990
  • NYU Grossman School of Medicine, New York, NY, Ph.D. Immunology 09/1986
  • Barnard College (Columbia University), New York, NY, BA Biology 05/1979
Biosciences Graduate Program Association
Awards & Honors
  • 2017 - Distinguished Faculty Award for Leadership in Program Innovation University of Chicago
  • 2018 - Tech Top 50 Women Crain's Chicago Business
  • 2019 - Louis M. Mendelson Award Lectureship American Academy of Allergy, Asthma and Immunology
  • 2019 - Notable Women in Health Care Crain's Chicago Business
  • 2019 - Siegel Lectureship UCLA
  • 2020 - Distinguished Fellow American Association of Immunologists
Publications

  1. Treatment of peanut allergy and colitis in mice via the intestinal release of butyrate from polymeric micelles. Nat Biomed Eng. 2022 Dec 22. View in: PubMed

  2. New and emerging concepts and therapies for the treatment of food allergy. Immunother Adv. 2022; 2(1):ltac006. View in: PubMed

  3. Interpreting success or failure of peanut oral immunotherapy. J Clin Invest. 2022 01 18; 132(2). View in: PubMed

  4. Host-Microbiota Interactions in the Esophagus During Homeostasis and Allergic Inflammation. Gastroenterology. 2022 02; 162(2):521-534.e8. View in: PubMed

  5. Modern World Influences on the Microbiome and Their Consequences for Immune-Mediated Disease. J Immunol. 2021 10 01; 207(7):1695-1696. View in: PubMed

  6. A wild approach to obesity prevention. Nat Metab. 2021 08; 3(8):1038-1039. View in: PubMed

  7. Fe, fi, fo, fum, I smell the diet of a healthy human. Cell. 2021 08 05; 184(16):4107-4109. View in: PubMed

  8. Early intervention and prevention of allergic diseases. Allergy. 2022 02; 77(2):416-441. View in: PubMed

  9. Engineered yeast tune down gut inflammation. Nat Med. 2021 Jul; 27(7):1150-1151. View in: PubMed

  10. Publisher Correction: Fiber-poor Western diets fuel inflammation. Nat Immunol. 2021 Jun; 22(6):795. View in: PubMed

  11. Publisher Correction: Fiber-poor Western diets fuel inflammation. Nat Immunol. 2021 Apr; 22(4):530. View in: PubMed

  12. Fiber-poor Western diets fuel inflammation. Nat Immunol. 2021 03; 22(3):266-268. View in: PubMed

  13. Fecal microbiome and metabolome differ in healthy and food-allergic twins. J Clin Invest. 2021 01 19; 131(2). View in: PubMed

  14. B cells and the microbiota: a missing connection in food allergy. Mucosal Immunol. 2021 01; 14(1):4-13. View in: PubMed

  15. Drugging the microbiome. J Exp Med. 2020 04 06; 217(4). View in: PubMed

  16. Origins of peanut allergy-causing antibodies. Science. 2020 03 06; 367(6482):1072-1073. View in: PubMed

  17. B cell superantigens in the human intestinal microbiota. Sci Transl Med. 2019 08 28; 11(507). View in: PubMed

  18. The Microbiome and Food Allergy. Annu Rev Immunol. 2019 04 26; 37:377-403. View in: PubMed

  19. Influences on allergic mechanisms through gut, lung, and skin microbiome exposures. J Clin Invest. 2019 02 25; 129(4):1483-1492. View in: PubMed

  20. Healthy infants harbor intestinal bacteria that protect against food allergy. Nat Med. 2019 03; 25(3):448-453. View in: PubMed

  21. Mechanism underlying the suppressor activity of retinoic acid on IL4-induced IgE synthesis and its physiological implication. Cell Immunol. 2017 Dec; 322:49-55. View in: PubMed

  22. Neonatal acquisition of Clostridia species protects against colonization by bacterial pathogens. Science. 2017 04 21; 356(6335):315-319. View in: PubMed

  23. The Influence of the Microbiome on Allergic Sensitization to Food. J Immunol. 2017 01 15; 198(2):581-589. View in: PubMed

  24. Extensively hydrolyzed casein formula alone or with L. rhamnosus GG reduces ?-lactoglobulin sensitization in mice. Pediatr Allergy Immunol. 2017 05; 28(3):230-237. View in: PubMed

  25. Cutting Edge: Lymphotoxin Signaling Is Essential for Clearance of Salmonella from the Gut Lumen and Generation of Anti-Salmonella Protective Immunity. J Immunol. 2017 01 01; 198(1):55-60. View in: PubMed

  26. Rapid and Efficient Generation of Regulatory T Cells to Commensal Antigens in the Periphery. Cell Rep. 2016 09 27; 17(1):206-220. View in: PubMed

  27. The composition of the microbiota modulates allograft rejection. J Clin Invest. 2016 07 01; 126(7):2736-44. View in: PubMed

  28. What's LPS Got to Do with It? A Role for Gut LPS Variants in Driving Autoimmune and Allergic Disease. Cell Host Microbe. 2016 May 11; 19(5):572-4. View in: PubMed

  29. The Microbiome, Timing, and Barrier Function in the Context of Allergic Disease. Immunity. 2016 Apr 19; 44(4):728-38. View in: PubMed

  30. Lactobacillus rhamnosus GG-supplemented formula expands butyrate-producing bacterial strains in food allergic infants. ISME J. 2016 Mar; 10(3):742-50. View in: PubMed

  31. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015 Apr 09; 161(2):264-76. View in: PubMed

  32. The role of the commensal microbiota in the regulation of tolerance to dietary allergens. Curr Opin Allergy Clin Immunol. 2015 Jun; 15(3):243-9. View in: PubMed

  33. Our interface with the built environment: immunity and the indoor microbiota. Trends Immunol. 2015 Mar; 36(3):121-3. View in: PubMed

  34. Cellular and molecular pathways through which commensal bacteria modulate sensitization to dietary antigens. Curr Opin Immunol. 2014 Dec; 31:79-86. View in: PubMed

  35. Health: The weighty costs of non-caloric sweeteners. Nature. 2014 Oct 09; 514(7521):176-7. View in: PubMed

  36. Commensal bacteria protect against food allergen sensitization. Proc Natl Acad Sci U S A. 2014 Sep 09; 111(36):13145-50. View in: PubMed

  37. TLR4 regulates IFN-? and IL-17 production by both thymic and induced Foxp3+ Tregs during intestinal inflammation. J Leukoc Biol. 2014 Nov; 96(5):895-905. View in: PubMed

  38. The role of commensal bacteria in the regulation of sensitization to food allergens. FEBS Lett. 2014 Nov 17; 588(22):4258-66. View in: PubMed

  39. Introduction to Special Issue on Food Allergy. Semin Immunopathol. 2012 Sep; 34(5):615-6. View in: PubMed

  40. Microbial regulation of allergic responses to food. Semin Immunopathol. 2012 Sep; 34(5):671-88. View in: PubMed

  41. Lymphotoxin regulates commensal responses to enable diet-induced obesity. Nat Immunol. 2012 Oct; 13(10):947-53. View in: PubMed

  42. Chitin microparticles for the control of intestinal inflammation. Inflamm Bowel Dis. 2012 Sep; 18(9):1698-710. View in: PubMed

  43. TL we meet again. Nat Immunol. 2011 Oct 19; 12(11):1027-8. View in: PubMed

  44. MyD88-dependent TLR1/2 signals educate dendritic cells with gut-specific imprinting properties. J Immunol. 2011 Jul 01; 187(1):141-50. View in: PubMed

  45. Regional mucosa-associated microbiota determine physiological expression of TLR2 and TLR4 in murine colon. PLoS One. 2010 Oct 22; 5(10):e13607. View in: PubMed

  46. Multivariate modeling identifies neutrophil- and Th17-related factors as differential serum biomarkers of chronic murine colitis. PLoS One. 2010 Oct 19; 5(10):e13277. View in: PubMed

  47. Vaccine-induced antibody isotypes are skewed by impaired CD4 T cell and invariant NKT cell effector responses in MyD88-deficient mice. J Immunol. 2009 Aug 15; 183(4):2252-60. View in: PubMed

  48. Toll-like receptor 4-mediated regulation of spontaneous Helicobacter-dependent colitis in IL-10-deficient mice. Gastroenterology. 2009 Oct; 137(4):1380-90.e1-3. View in: PubMed

  49. Immunologic responses to Vibrio cholerae in patients co-infected with intestinal parasites in Bangladesh. PLoS Negl Trop Dis. 2009; 3(3):e403. View in: PubMed

  50. Lymphocyte-dependent and Th2 cytokine-associated colitis in mice deficient in Wiskott-Aldrich syndrome protein. Gastroenterology. 2007 Oct; 133(4):1188-97. View in: PubMed

  51. Infection with parasitic nematodes confounds vaccination efficacy. Vet Parasitol. 2007 Aug 19; 148(1):14-20. View in: PubMed

  52. The Wiskott-Aldrich syndrome protein is required for the function of CD4(+)CD25(+)Foxp3(+) regulatory T cells. J Exp Med. 2007 Feb 19; 204(2):381-91. View in: PubMed

  53. Immune privilege in the gut: the establishment and maintenance of non-responsiveness to dietary antigens and commensal flora. Immunol Rev. 2006 Oct; 213:82-100. View in: PubMed
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