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
RELMß sets the threshold for microbiome-dependent oral tolerance. Nature. 2025 Jan 22. View Abstract
Enteric glia regulate Paneth cell secretion and intestinal microbial ecology. bioRxiv. 2024 Dec 23. View Abstract
ABO blood groups and galectins: Implications in transfusion medicine and innate immunity. Semin Immunol. 2024 Jul-Sep; 74-75:101892. View Abstract
Galectin-4 Antimicrobial Activity Primarily Occurs Through its C-Terminal Domain. Mol Cell Proteomics. 2024 May; 23(5):100747. View Abstract
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
C. difficile intoxicates neurons and pericytes to drive neurogenic inflammation. Nature. 2023 Oct; 622(7983):611-618. View Abstract
Blood group A enhances SARS-CoV-2 infection. Blood. 2023 08 24; 142(8):742-747. View Abstract
Bacterial amylases enable glycogen degradation by the vaginal microbiome. Nat Microbiol. 2023 09; 8(9):1641-1652. View Abstract
Vaginal microbiome-host interactions modeled in a human vagina-on-a-chip. Microbiome. 2022 11 26; 10(1):201. View Abstract
Innate immune Galectin-7 specifically targets microbes that decorate themselves in blood group-like antigens. iScience. 2022 Jul 15; 25(7):104482. View Abstract
The gut microbiome. Curr Biol. 2022 03 28; 32(6):R257-R264. View Abstract
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
Multi-kingdom ecological drivers of microbiota assembly in preterm infants. Nature. 2021 03; 591(7851):633-638. View Abstract
Ecological rules for the assembly of microbiome communities. PLoS Biol. 2021 02; 19(2):e3001116. View Abstract
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
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
Distribution and storage of inflammatory memory in barrier tissues. Nat Rev Immunol. 2020 05; 20(5):308-320. View Abstract
Understanding Competition and Cooperation within the Mammalian Gut Microbiome. Curr Biol. 2019 06 03; 29(11):R538-R544. View Abstract
Harnessing single-cell genomics to improve the physiological fidelity of organoid-derived cell types. BMC Biol. 2018 06 05; 16(1):62. View Abstract
The evolution of the host microbiome as an ecosystem on a leash. Nature. 2017 08 02; 548(7665):43-51. View Abstract
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
The evolution of cooperation within the gut microbiota. Nature. 2016 05 12; 533(7602):255-9. View Abstract
Another Reason to Thank Mom: Gestational Effects of Microbiota Metabolites. Cell Host Microbe. 2016 Apr 13; 19(4):425-7. View Abstract
Host Selection of Microbiota via Differential Adhesion. Cell Host Microbe. 2016 Apr 13; 19(4):550-9. View Abstract
The Regulation of Immunological Processes by Peripheral Neurons in Homeostasis and Disease. Trends Immunol. 2015 Oct; 36(10):578-604. View Abstract
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
Immunology: Starve a fever, feed the microbiota. Nature. 2014 Oct 30; 514(7524):576-7. View Abstract
An ecological network of polysaccharide utilization among human intestinal symbionts. Curr Biol. 2014 Jan 06; 24(1):40-49. View Abstract
Innate and adaptive immune connections in inflammatory bowel diseases. Curr Opin Gastroenterol. 2010 Nov; 26(6):572-7. View Abstract
Innate immune recognition of the indigenous microbial flora. Mucosal Immunol. 2008 Nov; 1 Suppl 1:S10-4. View Abstract
Role of toll-like receptors in tissue repair and tumorigenesis. Biochemistry (Mosc). 2008 May; 73(5):555-61. View Abstract
T cell responses to human endogenous retroviruses in HIV-1 infection. PLoS Pathog. 2007 Nov; 3(11):e165. View Abstract
Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88. Science. 2007 Jul 06; 317(5834):124-7. View Abstract
Prostaglandin-secreting cells: a portable first aid kit for tissue repair. J Clin Invest. 2007 Jan; 117(1):83-6. View Abstract
Why cancer and inflammation? Yale J Biol Med. 2006 Dec; 79(3-4):123-30. View Abstract
Retraction: Regulation of class II expression in monocytic cells after HIV-1 infection. J Immunol. 2006 Nov 01; 177(9):6561. View Abstract
Role of toll-like receptors in spontaneous commensal-dependent colitis. Immunity. 2006 Aug; 25(2):319-29. View Abstract
Role of the innate immune system and host-commensal mutualism. Curr Top Microbiol Immunol. 2006; 308:1-18. View Abstract
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
Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell. 2004 Jul 23; 118(2):229-41. View Abstract
Regulation of class II expression in monocytic cells after HIV-1 infection. J Immunol. 2001 Aug 15; 167(4):2331-42. View Abstract