Xavier Lab
@TheXavierLab
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Genes to functions. Microbiome in health & disease. Computational biology. Chemical biology. Innate & adaptive immunity. https://t.co/fsw4zVpmOE
Joined September 2020
We’re excited to see our latest @Nature paper online today! In collaboration with the Clardy lab, we identify a lipid from the Akkermansia muciniphila cell membrane that functions in homeostatic immunity 1/3.
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Exciting collab with @Honda1Kenya’s lab, out today in @Nature: A set of microbial strains taken from a human faecal donor can decolonize multidrug-resistant Enterobacteriaceae in the gut, including species associated with #IBD. (1/3)
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New in @NatImmunol! We identify pH sensor GPR65 as a controller of tissue inflammation in vivo and reveal functions of the I231L #IBD risk variant in multiple immune cell populations using newly-generated knock-in mice. 1/3
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Out now @ImmunityCP! Our comprehensive #singlecell atlas of >720k intestinal cells from #crohnsdisease patients uncovers transcriptional heterogeneity across tissues/inflammation states & identifies potential regulators of fibrosis. @MGH_RI.@broadinstitute.
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Out in @CellCellPress! We expand our understanding of maternal influences on the infant gut microbiome, with potentially profound implications for immune and neurodevelopment early in life @tvatanen @DamianPlichta @MoranYassour @MGH_RI @broadinstitute
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Check out our study in @NatureMicrobiol describing how oral microbe #Veillonella parvula switches its metabolism to utilize inflammatory nitrate & colonize the gut.
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New in @ImmunityCP, we investigate microbiome antigens that engage the immune system & discover a universally recognized Bacteroidales epitope, w/T cell responses shifting from tolerance to inflammation in IBD 👏.
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Excited to share our latest study uncovering gut microbes and microbial metabolites linked to cardiovascular health! We show that Oscillibacter is associated w/decreased cholesterol in human subjects & that these bacteria take up &metabolize cholesterol.
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ICYMI: Great study in @Nature from @DevlinLab and Jun Huh’s lab at @harvardmed identifying gut bacteria and enzymes that produce two anti-inflammatory bile acid metabolites, 3-oxoLCA and isoLCA. (1/3).
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1/3 Thrilled to share exciting new work in @Nature by @TouficMayassi, @li_chenhao, Åsa Segerstolpe, et al. Spatial profiling of mouse intestine reveals a landscape robust to perturbations in homeostatic drivers & adaptable in a spatially-restricted manner
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New in @nature, work with Kenya Honda’s lab identifying trypsin-degrading Paraprevotella strains that affect gut IgA levels and host pathogen sensitivity.
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Excited to share our latest @cellhostmicrobe study, led by @schirmer_lab & @mstrazar07, integrating #metagenomics, #metabolomics, & #culturomics to establish microbe-metabolite connections associated w/pediatric #UC disease severity @MGH_RI @broadinstitute.
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How does a single genetic variant impact multiple disease pathologies? Now online @PNASNews, we identify a link between Crohn’s disease (CD) risk allele SLC39A8 A391T & dietary Manganese to uncover a mechanism based on impaired intestinal barrier integrity
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Celebrating the establishment of The Gene Lay Institute of Immunology and Inflammation of Brigham and Women’s Hospital, Massachusetts General Hospital, and Harvard Medical School with institute directors—Dr. Vijay Kuchroo, Dr. Arlene Sharpe, and Dr. Ramnik Xavier.
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New in @NatureMicrobiol, we characterize the centenarian gut virome and identify enrichment of novel viral diversity, a population shift towards higher lytic activity, and a significant contribution of viral accessory genes to bacterial sulfur metabolism.
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Our latest work, out today @naturecomms & led by @mstrazar07 in collaboration with Mihai Netea and Quirijn de Mast, takes a multi-omics approach to uncover gut microbial factors & pathways that modulate host immune responses in a diverse Tanzanian cohort.
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New in @Nature! Emont et al describe a single-cell atlas of white adipose tissue & identify cell types linked to metabolic disease. Congrats to many colleagues, including Orr Ashenberg in the Klarman Cell Observatory @broadinstitute (1/2).
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New in @cellhostmicrobe! We investigate the gut #microbiome as an integrator of environmental risk in developing colorectal cancer, identifying microbial profiles associated with distinct premalignant colon polyps & links to diet and medication history.
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Online now! The Smillie Lab @MGH_RI & @broadinstitute used evolutionary approaches to discover hundreds of ancient, diverse, and ubiquitous bacterial strains that expand and outcompete health-associated counterparts during IBD (1/2).
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Online @ImmunityCP! @mstrazar07 & colleagues identify HLA-II binding peptides w/monoallelic #immunopeptiomics & develop a #machinelearning tool (CAPTAn) that predicts peptide antigens based on HLA-II affinity and source protein sequence.
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Multi-omic profiling in IBD patients initiating biologic therapy identifies remission-associated gut microbial features. Our findings provide a foundation for more individualized selection of optimal therapeutic agents. Online now @cellhostmicrobe:.
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Featured on the cover of @CellCellPress!.@tvatanen, @QiYanAng & colleagues at Nestle Research & @icddr_b uncover succession of B. longum clades in gut #microbiome of infants from Dhaka, Bangladesh spanning dietary changes in the first two years of life
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Interested in #antigen discovery? The Xavier lab is developing prediction tools like these! . Check out the papers linked below:. BOTA: hBOTA: CAPTAn:
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Excited to share our latest work determining biological functions of disease risk genes! @li_chenhao @TouficMayassi @helen_lin2113 @iamkoushik_kg @jaiswal_ok .@MGH_RI @MGHMolBio @broadinstitute.
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How do ER stress response pathways maintain cell survival and function in health and disease? Out now @Sciencemagazine, we identify an arm of the PERK-eIF2α UPR pathway that determines cell fate during #ERstress.
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Out now in @GenomeMedicine! Read about our latest efforts, led by @RebLWalker, exploring associations between diet, lifestyle, & cardiometabolic disease phenotypes w/the gut #microbiome among the @FraminghamStudy participants.
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Out today in @cellhostmicrobe! In work led by @ericmichbrown and @HASCiencia we show that ADP-ribosyltransferases are phage-associated proteins plentiful in commensal bacteria in the human gut microbiome & confer fitness advantages in the gut. (1/4)
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Which #bacteria are too close for comfort and how does the mouse gut sense them? . Britta, @mstrazar07, RJX and @mssanjavickovic develop SHM-seq, a new #spatial host and #microbiome sequencing technology. Learn more in Nat Biotech:
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In a creative study in @NatureMedicine, @QuintanaLabHMS develops yeast-based engineeredprobiotics that suppress intestinal inflammation in mouse models of IBD as effectively as standard therapies while mitigating off-target effects. 1/2
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Collaboration with @TheColonnaLab & others, in press at @Dev_Cell: The FGFR1OP gene, implicated in #Crohns, contributes to intestinal barrier function by modulating the actin cytoskeleton in crypt cells. (1/2)
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In a collaboration with Kenya Honda’s lab to characterize gut microbiomes of centenarians we identified a novel biosynthetic pathway producing a potent antimicrobial 2° bile acid that may contribute to healthy aging. @DamianPlichta 👋.
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New in @JExpMed, single-cell transcriptomic & VDJ profiling of the colon plasma cell (PC) repertoire reveals #microbiome-specific PC responses in #ulcerativecolitis (UC) patients. @basak_ersln @AJHudak @ericmichbrown @broadinstitute @MGHMolBio.
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Online today in @cellhostmicrobe! We characterized transcriptional signatures of host cells harboring different phenotypic states of Mycobacterium #tuberculosis (Mtb) and identified the MMGT1-GPR156 axis as a host regulator of Mtb persistence.
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New in @molpsychiatry! We show #schizophrenia risk variant in SLC39A8 alters protein #glycosylation in the #brain—a potentially reversible biochemical change & therapeutic target. (1/2).
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We are excited to share work by @johannesfscheid, @cobarnes27, and @basak_ersln with @bjorkmanlab, Regev lab, and @PaulBieniasz lab characterizing B cell responses against #SARSCoV2. (1/3) @broadinstitute .Online @CellCellPress:
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Check out our new preview piece on unexpected T cells activated by fungi - the latter are enriched in Crohn's Disease and some cheeses, too. #cheese #crohnsdisease #fungi #tcells.
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Exciting work from our collaboration with John Rioux @ICMtl is out now @GenomeMedicine. A functional screen of #IBD #genes in intestinal epithelial cells reveals key biological.functions. (1/3). @broadinstitute @mgh_ri.
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Congratulations to co-first authors @ericmichbrown and @HASCiencia on their ADPRT paper making it on the @cellhostmicrobe list of editors' favorite articles in 2021! .
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Out now in Genome Biology! @mstrazar07 led our latest work in collaboration with Vera Mourits, which reveals specific gut microbes and their products that may alter specific and trained immune responses. @broadinstitute (1/5)
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New collaborative work with @KuchrooLab, @YosefLab & others reporting the requirement of IL-23R signaling in Th1-like cells to induce pathogenic tissue inflammation – now online in @ImmunityCP.
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We want to recognize @tvatanen for his appointment as Associate Professor at @helsinkiuni .@HiLIFE_helsinki! During his time in our group, Tommi made incredible contributions to #microbiome research (highlighted below), & we’re excited to see all the great science to come! (1/7).
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CONGRATULATIONS GARY!.
Say good morning to our new medicine laureate 🎉. Gary Ruvkun was woken up in the early hours to the news he had been awarded the 2024 Nobel Prize in Physiology or Medicine. Stay tuned for our interview with him, coming soon.
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Out now @GenomeBiology, we identify gut microbe-derived metabolites that modulate the #ERstress response, suggesting a potential role in maintaining gut ER and intestinal epithelial cell homeostasis. @broadinstitute @MGH_RI (1/5).
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(1/5) Excited to share this collab with the Cravatt lab at @scrippsresearch! A structurally diverse library of photoreactive, stereoselective chemical probes can be used for high-throughput #proteomics experiments in living systems.
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Timely review of bioactive lipids derived from gut bacteria and their impacts on host immunity and metabolism – published yesterday in Cell Host & Microbe with @ericmichbrown and Jon Clardy @broadinstitute @MGHMolBio @MGH_RI.
Gut microbiome lipid metabolism and its impact on host physiology. Featured Review from @ericmichbrown Clardy @HMS_BCMP @TheXavierLab examining # lipids that #microbiome species can synthesize and their function on host physiology
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Thanks for the great write up!.
Researchers from the Smillie Lab at @MGH_RI and the @broadinstitute identifies particular strains of gut bacteria that are more prominent in patients with inflammatory bowel disease (IBD)
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👏Congrats to @SashaZhernakova, @jingyuan_fu & many other colleagues on the new Dutch Microbiome Project paper, out yesterday in @nature! (1/3).
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Out now in @NatureComms: our single-cell atlas of the esophagus during #EoE highlights previously unknown features of this inflammatory condition, including an important role for mast cells in active disease.
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Out today in @CellReports! We show that counter-regulation of lipid membrane dynamics by mammalian host cells and bacteria during xenophagy modulates an innate defense response (1/6):.
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As we welcome summer and warmer weather, we'd like to give a big congratulations and good luck to all the RAs who are moving on to graduate school, medical school, and the next step in their career. We loved celebrating you and all your hard work! 👏👏👏🎉 (1/2)
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Exciting new #preprint in untargeted #metabolomics! With Xavier lab postdoc @mstrazar07, @samgoldman19 @cwcoley & others at MIT built a neural architecture called MIST to annotate mass spectra peaks beyond known standards.
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Join us in congratulating Dr. Ramnik Xavier, who has been named on Clarivate Analytics’ Web of Science Group's 2020 annual list of Highly Cited Researchers! @broadinstitute @MGH_RI
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Online today in @AgingCell, collaborative work with Albert Shaw using multi-omics data to uncover age related #metabolomic & #transcriptomic signatures associated with #influenza vaccine response. @ChihHungChou @YaleMed @hipcProject @MGH_RI @broadinstitute
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Congratulations to Xavier Lab RA Dallis Sergio on her admittance to @BrownUniversity's Pathobiology #PhD program! We are sad to see you go, but hope that you enjoy your time at Brown. Good luck 🎉!!. @BrownUPathoGP #phdlife #xavierlabalumni #pathobiology.
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A wonderful spotlight on our lab member, @AJHudak, who worked with @johannesfscheid and others on our recent @CellCellPress paper characterizing B cell responses against #SARSCoV2.
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Out today! In a collaboration w/the Clardy lab, we show that the difference between mounting a tolerogenic or inflammatory response to R. gnavus strains depends on the presence or absence of a capsule, respectively. @ericmichbrown @broadinstitute @MGH_RI .
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Core @broadinstitute member Ramnik Xavier named as the next Director of the Klarman Cell Observatory (KCO). Launched in 2012 under the leadership of Aviv Regev and support from the Klarman Family Foundation, the KCO became the driving force in the single-cell biology revolution.
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Busy day in the Xavier Lab! Now in @CellCellPress:. Results of highly collaborative work to develop a massively parallel base-editing platform for variant-to-function studies in primary cells! . @broadinstitute @harvardmed @MGHMolBio @MGH_RI .
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We’re excited to introduce MMUPHin, new software developed & validated with the @hutlab that enables normalization & statistical meta-analysis across #microbiome datasets! Full @GenomeBiology study here: .
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Congratulations @schirmer_lab, @mstrazar07, and colleagues for the cover feature on the cover of the latest @cellhostmicrobe issue!!! . Thanks to @LSE_Duygu for this beautiful work!.
Show your love for microbiology today and explore our new issue, now live!
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In our latest @CellReports study, we dissect #transcriptomic, #proteomic, and #metabolic dynamics in Beclin1-dependent models of deficient and hyperactive #autophagy to understand mechanisms of autophagy-regulated inflammatory signaling.
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Delighted to have been a part of a new & exciting study that will accelerate the discovery of molecules and phenotypic associations from untargeted #metabolomics data! Read @Pdorrestein1’s thread describing the work:.
I am so excited that @em_gentry1 (@gentrylab) paper on reverse metabolomics to discover molecules is published, a project started in 2018. She found many new lipids and bile acids in humans. (online What is reverse metabolomics?.
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Congratulations to the Xavier lab members who were awarded the Broad Institute’s 2020 Excellence and Achievement Awards: Andrew Bolze, Andrew Hudak, Betsabeh Tusi, Haroon Kalam, Johannes Scheid, Sung-Moo Park, and Kawther Abu Elneel! (1/2).
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New @biorxivpreprint! This collab with Ben Cravatt, @brumelillo, @SchreiberStuart and others used photo-stereoprobes to engage hard-to-target proteins in #highthroughput screening assays, which has applications in #drugdiscovery. See first author @d_ogasa’s detailed summary.
Excited to share my postdoc work in Cravatt lab & Schreiber lab!.We described photo-stereoprobes, DOS-inspired photo-reactive probes, for expanding the ligandable proteome. 🧵.
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Congratulations to @ReubenRyanCano on the next step in his scientific career! We will miss you in the lab but are excited for your bright future as an MD/PhD.
If you had told me when I was in community college that I’d be doing research here one day, I wouldn’t have believed you. So grateful for all the friends, life lessons, and knowledge I’ve gained in the @TheXavierLab at the @broadinstitute. Excited for the next chapter @DukeMSTP!
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The Center for Integrated Solutions in Infectious Disease is seeking an Assistant Professor to lead groundbreaking research @ the intersection of basic science & clinical practice! Are you passionate about transforming our understanding of human infection & immunity? (1/2)
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The Center for Computational and Integrative Biology and the Center for Immunology and Inflammatory Diseases are seeking an Assistant Professor pursuing innovative approaches to fundamental problems in immunology with a focus on clinical applications.
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The Xavier Lab hosted its annual team retreat last week and everyone had a blast! We all had a beachin' good time, thanks to @LamplighterBrew and La Bonne Maison for great food and drinks.
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Xavier lab postdoc, Masa Kanai, was one of the leaders at @broadinstitute responsible for the second analysis of genetic factors influencing #COVID-19, published in Nature! (cont.).
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Our collaborative @J_A_C_S study reports a small but critical correction to the structure of a #lipid immunogen for #LymeDisease, with implications for vaccine efforts and #immune activation by #bacterial galactolipids. @broadinstitute @MGH_RI .
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Our latest paper identifying positive allosteric modulators of GPR65 that alter #cytokine signaling networks is out in @ScienceAdvances & was driven by an RA in the lab, who is moving on to a PhD program at UPenn! Congrats Ilona & coauthors!.
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Insightful article on recent advances in #IBD research, featuring studies on novel mechanisms and genetic and microbial associations that promise more effective, individualized therapies. (1/4).
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Why does smoking affect #Crohns and #ulcerativecolitis patients differently? New in. @IBDJournals: We profiled both shared and CD/UC-specific effects of #smoking on gene methylation and transcription, with emphasis on immune and inflammatory pathways.
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As summer winds down, we are saying goodbye to all of our "graduating" RAs. Although we have tweeted our goodbyes to most of them, we'd like to formally say congratulations and good luck to all of the talented junior scientists who are leaving our lab this year.
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Are you a scientist interested in joining a unique team of amazing, creative people pushing scientific frontiers? The Xavier Lab is seeking postdocs who are interested in immunology, molecular biology, biochemistry, or computational biology! . Apply here: .
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New in @CellCellPress: An adjuvant that corrects migratory defects in the dendritic cells of elderly mice. #Vaccines given with this adjuvant can induce anti-tumor #immunity in both young and old mice. Check out first author @Dzhivaki’s walkthrough of the findings!.
A detailed tweetorial on our new study describing vaccines that work in the old and young by Dania Zhivaki. @DZhivaki .
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‘Conditioned immunity’ integrates multifaceted mechanisms by which the #microbiome modulates #immunity. Read our opinion piece in the new @TrendsImmuno special issue on #SystemsImmunology!. @broadinstitute @MGHMolBio @MGH_RI.
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Out now in @PLOSBiology! Guadalupe Jasso and @jaiswal_ok et al. generate a single-cell transcriptomic atlas of the intestinal stromal compartment in mice. (1/3).
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Great work from one of our hard-working research associates!.
My first publication is out today in @cellhostmicrobe ! Exciting work led by @ericmichbrown and @HASCiencia investigating gut microbiome ADP-ribosyltransferases which serve as phage-encoded fitness factors. @TheXavierLab @broadinstitute @Novartis (1/2).
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Check out the Broad news story on our recently published work in @GenomeBiology and @CellReports examining how the #BCG vaccine gives specific protection against #TB as well as non-specific protection against other pathogens. @broadinstitute @mgh_ri (1/2).
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@mrtbrandt and colleagues at @broadinstitute @MGHMolBio @MGH_RI applied translational genetics to a rare CARD9 missense variant linked with dermatophytosis and uncovered a signaling switch that controls tissue immunity against fungal infection, now online in @CellReports!.
Translational genetics identifies a phosphorylation switch in CARD9 required for innate inflammatory responses
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A successful (albeit cloud and wet) lab hike at Mount Wachusett this weekend with some of our esteemed lab members!
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Excited to be part of this study from @matejoresic's group on #bileacid metabolism in development of type 1 diabetes!.
New paper! We used #GSMM to integrate longitudinal #gutmicrobiome and #bileacid data in children en route to #T1D & found that 2ndary BA pathways may contribute to T1D pathogenesis. Thx particularly @partho_phd & @SantoLamichane!.#lipidomics #metabolomics.
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Out now in @GenomeMedicine, Damian Plichta and coauthors report on an initial characterization of gut microbiome ecology in immunoglobulin G4-related systemic disease (IgG4-RD) and secondary sclerosing cholangitis (SSc) (1/4).
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New workflow developed by @tvatanen and colleagues to assemble and annotate #microbial #genomes that combines deep-learning functional predictions with commonly used orthology-based annotations: @broadinstitute @MGHMolBio @MGH_RI.
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Give a warm welcome to @adrianbebenek, our new PhD student in the Harvard #ChemBio program! Adrian is interested in using structural biology/biophysics to link #autoimmune disease-associated genetic #variants w/protein function & developing tools to modulate immune activation.
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New in @NatureGenet! We measured cell type- and state-dependent variance in HLA gene regulation using scHLApers, our pipeline for single-cell quantification of HLA expression that uses personalized reference #genomes to account for the HLA genes’ high degree of #polymorphism.
Excited that our single-cell eQTL study of HLA genes is out now in @NatureGenet! ⭐️ .Huge thx to @soumya_boston @saorisakaue @yluo86 for their guidance. Check out this great News & Views by the Gaffney lab describing the key points:
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New study from @TheColonnaLab using #singlecell transcriptional and #metabolomic profiling to dissect metabolic pathways in ILC3-driven immune responses – out now in @PNASNews!.
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New in @NatureAging, Xavier lab postdoc @JLindbohm investigates the causal role of #immune system and blood-brain-barrier dysfunction in #dementia & suggests anti-inflammatory drugs could be repurposed for dementia-causing diseases.
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Now online from @SciImmunology! @KateJeffrey1 and colleagues show that the enteric #virome actively shapes mucosal immunity, with #IBD viromes eliciting and non-IBD viromes suppressing inflammation.
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(1/3) This important collab with @WangXiaoLab, out now in @NatureBiotech, promises to expand the potential of mRNA-based therapies. The paper describes a method for systematic chemical modification and screening of synthetic #mRNAs to optimize their translation efficiency.
Chapter 2 of branched RNA: chemically modified branched cap for multi-capped mRNA and capped circular RNA (QRNA)--the cellular translation machinery is surprisingly tolerant of unnatural structures! Beyond enhanced performance, the mechanism is intriguing:
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Could personalized fecal microbiota transplants (FMTs) help maintain remission in patients with Crohn’s disease (CD)? In a study now online @AGA_Gastro, we assess gut microbiome composition changes in CD patients receiving FMT while in remission. (1/2).
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Our recent findings from analyses of the gut microbiome’s roles in #IBD therapy response ( and in healthy aging ( further support that 3-oxoLCA and isoLCA promote human health. (3/3).
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How are TFEB and its targets regulated? Now online .@CellReports, we unravel localization- and stimulation-specific responses to TFEB and uncover a connection between BHLHE40/BHLHE41, TFEB and lysosomes. @broadinstitute @MGH_RI .
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Latest collaboration w/ the Clardy lab finds another immunogenic #microbial #lipid: CaLGL-1 produced by C. aerofaciens at low pH. Structures, target, formation, and signaling reported here @harvardmed @broadinstitute @MGHMolBio @MGH_RI.
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Out today: A review discussing how emerging technologies, like #singlecell genomics, shed light on the processes that define the human #Bcell receptor repertoire and how they can contribute to disease. A must-read for folks interested in autoimmunity! . Congrats, @jdeguine.
Jacques Deguine & Ramnik Xavier @TheXavierLab review how technological advances have expanded our ability to map immune receptor repertoires across B cell states in health & disease, revealing distinct processes involved in the generation of autoantibodies
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Out yesterday @CellReports! We are using single-cell transcriptomic profiling in monocytes to uncover mechanisms of #BCG #trained #immunity. (1/4). @broadinstitute @mgh_ri.
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Thanks to Jonathan Braun @IBDCedarsSinai for highlighting our IBD study on biomarkers for response to treatment in his thoughtful commentary in .@cellhostmicrobe about the contributionsof microbial communities to host phenotypes! .
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If you missed today's Keynote talk at the Microbiome Virtual International Forum, you can catch a replay here tomorrow:
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