Information

Related Research Units

Research Overview

Lab: SRN Lab

The goal of the Rakoff-Nahoum lab is a comprehensive understanding of the host-associated microbiota at various levels of biological organization: from genes to molecules to organisms to ecosystems, and importantly, the determination of cause and effect. To achieve this, we couple empirical approaches with ecological and evolutionary frameworks. We use the tools of classic bacterial genetics of gut anaerobes including the cultivation, random and directed mutagenesis of individual members of the mammalian microbiota (Bacteroides, Firmicutes, Actinobacteria), in vitro and in vivo experimental and gnotobiotic systems to study the adaptation of gut bacteria to the environment, computational approaches to microbiome ecology, and high throughput in vitro pipelines for the cultivation, genetic, chemical and phenotypic analysis of the effects of members of the microbiota on each other and the host, with focus on innate and adaptive immunity.

Current focuses in the Rakoff-Nahoum lab center in six non-mutually exclusive dimensions: 1) genetic and molecular mechanisms of cooperation and competition among the gut and female reproductive tract microbiome, 2) the role of microbial metabolites in gut microbial ecology, 3) the glycobiology of host-microbiome interactions, 4) microbiome ecology in human populations, focusing on pediatric health and disease, 5) metabolism of dietary and microbial bioactive molecules by the microbiome and impact on host innate and adaptive immunity, 6) the role of gut and FRT community function in inflammation.

Research Background

Dr. Rakoff-Nahoum received B.A.’s in Biology and Religious Studies at Brown University, and both an M.D. and Ph.D in Immunobiology from Yale University, performing graduate work with Ruslan Medzhitov, studying pattern recognition of the microbiota. During clinical training in Pediatrics in the Boston Combined Residency Program and in Pediatric Infectious Diseases at Boston Children’s Hospital, he performed postdoctoral work with Laurie Comstock, studying social evolution in gut microbial communities. Dr. Rakoff-Nahoum’s lab is supported by an NIH Director’s New Innovator Award,the Pew Scholars Program in Biomedical Sciences, a Basil O’Connor Award from the March of Dimes, and a Career Award for Medical Scientists from the Burroughs Wellcome Foundation. Dr. Rakoff-Nahoum’s clinical focus is in the immunocompromised infectious diseases pediatric population.

 

Education

Medical School

Yale University School of Medicine
2009 New Haven CT

Internship

Pediatrics Boston Combined Residency Program (BCRP)
2010 Boston MA

Residency

Pediatrics Boston Combined Residency Program (BCRP)
2012 Boston MA

Fellowship

Pediatric Infectious Diseases Boston Children's Hospital
2015 Boston MA

Publications

  1. RELMß sets the threshold for microbiome-dependent oral tolerance. Nature. 2025 Jan 22. View Abstract
  2. Enteric glia regulate Paneth cell secretion and intestinal microbial ecology. bioRxiv. 2024 Dec 23. View Abstract
  3. ABO blood groups and galectins: Implications in transfusion medicine and innate immunity. Semin Immunol. 2024 Jul-Sep; 74-75:101892. View Abstract
  4. Galectin-4 Antimicrobial Activity Primarily Occurs Through its C-Terminal Domain. Mol Cell Proteomics. 2024 May; 23(5):100747. View Abstract
  5. Stress Ulcer Prophylaxis Versus Placebo-A Blinded Pilot Randomized Controlled Trial to Evaluate the Safety of Two Strategies in Critically Ill Infants With Congenital Heart Disease. Pediatr Crit Care Med. 2024 Feb 01; 25(2):118-127. View Abstract
  6. C. difficile intoxicates neurons and pericytes to drive neurogenic inflammation. Nature. 2023 Oct; 622(7983):611-618. View Abstract
  7. Blood group A enhances SARS-CoV-2 infection. Blood. 2023 08 24; 142(8):742-747. View Abstract
  8. Bacterial amylases enable glycogen degradation by the vaginal microbiome. Nat Microbiol. 2023 09; 8(9):1641-1652. View Abstract
  9. Vaginal microbiome-host interactions modeled in a human vagina-on-a-chip. Microbiome. 2022 11 26; 10(1):201. View Abstract
  10. Innate immune Galectin-7 specifically targets microbes that decorate themselves in blood group-like antigens. iScience. 2022 Jul 15; 25(7):104482. View Abstract
  11. The gut microbiome. Curr Biol. 2022 03 28; 32(6):R257-R264. View Abstract
  12. Strain-level fitness in the gut microbiome is an emergent property of glycans and a single metabolite. Cell. 2022 02 03; 185(3):513-529.e21. View Abstract
  13. Multi-kingdom ecological drivers of microbiota assembly in preterm infants. Nature. 2021 03; 591(7851):633-638. View Abstract
  14. Ecological rules for the assembly of microbiome communities. PLoS Biol. 2021 02; 19(2):e3001116. View Abstract
  15. Combined immunodeficiency due to a mutation in the ?1 subunit of the coat protein I complex. J Clin Invest. 2021 02 01; 131(3). View Abstract
  16. Stress ulcer prophylaxis versus placebo-a blinded randomized control trial to evaluate the safety of two strategies in critically ill infants with congenital heart disease (SUPPRESS-CHD). Trials. 2020 Jun 29; 21(1):590. View Abstract
  17. Distribution and storage of inflammatory memory in barrier tissues. Nat Rev Immunol. 2020 05; 20(5):308-320. View Abstract
  18. Understanding Competition and Cooperation within the Mammalian Gut Microbiome. Curr Biol. 2019 06 03; 29(11):R538-R544. View Abstract
  19. Harnessing single-cell genomics to improve the physiological fidelity of organoid-derived cell types. BMC Biol. 2018 06 05; 16(1):62. View Abstract
  20. The evolution of the host microbiome as an ecosystem on a leash. Nature. 2017 08 02; 548(7665):43-51. View Abstract
  21. Interplay between microbial d-amino acids and host d-amino acid oxidase modifies murine mucosal defence and gut microbiota. Nat Microbiol. 2016 07 25; 1(10):16125. View Abstract
  22. The evolution of cooperation within the gut microbiota. Nature. 2016 05 12; 533(7602):255-9. View Abstract
  23. Another Reason to Thank Mom: Gestational Effects of Microbiota Metabolites. Cell Host Microbe. 2016 Apr 13; 19(4):425-7. View Abstract
  24. Host Selection of Microbiota via Differential Adhesion. Cell Host Microbe. 2016 Apr 13; 19(4):550-9. View Abstract
  25. The Regulation of Immunological Processes by Peripheral Neurons in Homeostasis and Disease. Trends Immunol. 2015 Oct; 36(10):578-604. View Abstract
  26. Analysis of gene-environment interactions in postnatal development of the mammalian intestine. Proc Natl Acad Sci U S A. 2015 Feb 17; 112(7):1929-36. View Abstract
  27. Immunology: Starve a fever, feed the microbiota. Nature. 2014 Oct 30; 514(7524):576-7. View Abstract
  28. An ecological network of polysaccharide utilization among human intestinal symbionts. Curr Biol. 2014 Jan 06; 24(1):40-49. View Abstract
  29. Innate and adaptive immune connections in inflammatory bowel diseases. Curr Opin Gastroenterol. 2010 Nov; 26(6):572-7. View Abstract
  30. Toll-like receptors and cancer. Nat Rev Cancer. 2009 Jan; 9(1):57-63. View Abstract
  31. Innate immune recognition of the indigenous microbial flora. Mucosal Immunol. 2008 Nov; 1 Suppl 1:S10-4. View Abstract
  32. Role of toll-like receptors in tissue repair and tumorigenesis. Biochemistry (Mosc). 2008 May; 73(5):555-61. View Abstract
  33. T cell responses to human endogenous retroviruses in HIV-1 infection. PLoS Pathog. 2007 Nov; 3(11):e165. View Abstract
  34. Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88. Science. 2007 Jul 06; 317(5834):124-7. View Abstract
  35. Prostaglandin-secreting cells: a portable first aid kit for tissue repair. J Clin Invest. 2007 Jan; 117(1):83-6. View Abstract
  36. Why cancer and inflammation? Yale J Biol Med. 2006 Dec; 79(3-4):123-30. View Abstract
  37. Retraction: Regulation of class II expression in monocytic cells after HIV-1 infection. J Immunol. 2006 Nov 01; 177(9):6561. View Abstract
  38. Role of toll-like receptors in spontaneous commensal-dependent colitis. Immunity. 2006 Aug; 25(2):319-29. View Abstract
  39. Role of the innate immune system and host-commensal mutualism. Curr Top Microbiol Immunol. 2006; 308:1-18. View Abstract
  40. Detection of T lymphocytes specific for human endogenous retrovirus K (HERV-K) in patients with seminoma. AIDS Res Hum Retroviruses. 2006 Jan; 22(1):52-6. View Abstract
  41. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell. 2004 Jul 23; 118(2):229-41. View Abstract
  42. Regulation of class II expression in monocytic cells after HIV-1 infection. J Immunol. 2001 Aug 15; 167(4):2331-42. View Abstract

Contact Seth Rakoff-Nahoum