thexavierlab.bsky.social

sciencedirect.comsciencedirect.com

Our latest analysis of microbiome-reactive T cells, which revealed a unique, pro-inflammatory TMIGD2-hi subset of Th17 cells that expands in IBD and enriches spatially at the epithelium, is now online @ImmunityCP! www.sciencedirect.com/science/arti... @broadinstitute.org @mgbresearch.bsky.social

broadinstitute.orgKlarman FellowshipThe Broad Institute of MIT and Harvard seeks exceptional applicants for the Klarman Fellowship, a postdoctoral research program within the GaMBiT Initiative.

Applications are open for the Klarman Fellowship at @broadinstitute.org! We are looking for postdoctoral researchers to join the GaMBiT Initiative to develop innovative technologies that translate human genetic discoveries into disease mechanisms, biomarkers, and therapeutic leads.

broadinstitute.orgKlarman FellowshipThe Broad Institute of MIT and Harvard seeks exceptional applicants for the Klarman Fellowship, a postdoctoral research program within the GaMBiT Initiative.

Learn more and apply here: www.broadinstitute.org/gambit/gambi...

nature.comA structure-informed deep learning framework for modeling TCR-peptide-HLA interactions - Nature CommunicationsBioinformatics tools can be used for modelling T cell receptor (TCR)-peptide-Human Leukocyte antigen (HLA) interactions since these are important in the initiation of immune responses. Here the author...

New work with Caroline Uhler's lab is out in @natcomms.nature.com. We developed StriMap, a deep learning model to predict TCR–peptide–HLA interactions, and used it to uncover bacterial peptides that activate an ankylosing spondylitis-associated TCR. www.nature.com/articles/s41...

@broadinstitute.org @mgbresearch.bsky.social

academic.oup.comPepGen: conditional generation of peptides for MHC bindingAbstractMotivation. Peptide-MHC II binding drives adaptive immunity, yet discovery of novel binder peptides remains challenging due to open binding grooves

27 Aug

We teamed up with Harri Lahdesmaki at Alto University to develop & validate PepGen, the first fully generative model capable of synthesizing MHCII peptide binders conditioned on allele, partial sequences, & continuous affinity Read the results here: academic.oup.com/bioinformati...

27 Aug

@broadinstitute.org

biorxiv.orgMulti-Modal Foundation Model with Whole-Slide Attention Enables Transferrable Digital Pathology at Single-Cell ResolutionPaired histopathology and spatial transcriptomics data are advancing our understanding of tissue biology and disease, but modeling both modalities at single-cell resolution while mapping local and dis...

27 Aug

New preprint from our collaboration with Caroline Uhler and @broadinstitute.org on TissueFormer, a new tool for predicting spatial gene expression from histology images at cellular resolution www.biorxiv.org/content/10.6...

nature.comAntisense transcription reveals disease-associated adaptations in the human gut microbiome - Nature MicrobiologyMetastrand integrates strand-aware metatranscriptomic and metagenomic data to distinguish microbial sense from antisense transcription at gene-level resolution, and a use case study highlights the imp...

11 Aug

Out now in @natmicrobiol.nature.com Marie Pust and colleagues developed metastrand, a tool to quantify strand-specific transcription in microbiomes at gene-level resolution, and used it to reveal microbial adaptations associated with IBD. www.nature.com/articles/s41... #metastrand #IBD

11 Aug

First author Marie is now the Group Leader in Microbiome Studies at the Kennedy Institute of Rheumatology, University of Oxford – Congratulations, Marie!

doi.orgADAMTS14 is a Novel Modulator of Fibroblast Mechanoactivation in Pulmonary FibrosisAbstractRationale. Yes-associated protein (YAP)-mediated fibroblast mechanoactivation is an important driver of fibrosis in idiopathic pulmonary fibrosis (

4 Aug

New work with Ben Medoff's lab, online now! ADAMTS14 regulates YAP-driven fibroblast activation in IPF. We define an ADAMTS14–collagen V–focal adhesion pathway that contributes to $fibrosis, highlighting ADAMTS14 as a potential therapeutic target. doi.org/10.1093/ajrc...

4 Aug

Building on our previous lung atlas, which identified pathogenic CTHRC1-high #fibroblasts enriched within fibrotic niches, this study further defines the molecular mechanisms that drive IPF. doi.org/10.1016/j.xg... @mgbresearch.bsky.social @broadinstitute.org

doi.orgRedirecting

nature.comStudying vanishing dietary diversity before it is lost: the World Diet Initiative - Nature MedicineHeritage diets are disappearing as food systems homogenize; their effects on immunity, metabolism and host–microbiome biology remain poorly understood. The World Diet Initiative offers a framework to ...

16 July

Check out this @NatureMedicine Comment about the importance of studying heritage diets and the World Diet Initiative’s efforts to translate dietary diversity into health benefits for the global community: www.nature.com/articles/s41...

18 June

Join us and @genelayinstitute.bsky.social on July 31st for the Annual Symposium! This year's speakers include Marco Colonna, Shimon Sakaguchi, Stefani Spranger, and Gabriel Victora. Register using the QR code in the flyer! #inflammation #immunity #disease #genelayinstitute

8 June

It's that time of year again--we are saying goodbye to more of our youngest and brightest lab members as they transition to the next steps of their careers, either in grad school or in other institutions. This week, we are saying goodbye to Anna, Regan, and Tanvi.

8 June

Good luck at UCSF (Anna), University of Washington (Regan), and MIT (Tanvi). We will miss you!

28 May

New website launch for the World Diet Initiative—an international effort to map global dietary patterns and their impacts on human health. The site is now accepting heritage diet submissions to build the open-access World Diet Atlas. www.worlddietinitiative.org

@cp-cellhostmicrobe.bsky.social

22 May

Congratulations to postdoc Sacha Lebon on publishing his graduate work! Using single-cell profiling, his study reveals how intestinal epithelial stem cells sense and respond to bacterial invasion. www.nature.com/articles/s41...

thexavierlab.bsky.social reposted

Cell Host & Microbe

19 May

Early-life interventions & airway microbiome Nasal microbial gene atlas in infants w/cystic fibrosis. Hypertonic saline inhalation reshapes microbiome, selects salt-tolerant H. influenzae & ⬆️transporters linked to antibiotic tolerance @thexavierlab.bsky.social www.cell.com/cell-host-mi...

cell.comAn infant nasal microbial gene atlas uncovers intervention-driven microbiome shifts and salt-resistant pathogen expansionSteinberg et al. generated an infant nasal microbial gene atlas using samples from infants with and without cystic fibrosis. Frequent hypertonic saline inhalation reshapes airway microbiome function, ...

thexavierlab.bsky.social reposted

Cell Host & Microbe

@cp-cellhostmicrobe.bsky.social

19 May

What the nose knows of cystic fibrosis microbes and hypertonic saline Bouzek Previews work by @thexavierlab.bsky.social presenting microbial gene atlas of nasopharyngeal swabs in infants w/cystic fibrosis & healthy controls & IDing impacts of clinical interventions www.cell.com/cell-host-mi...

cell.comWhat the nose knows of cystic fibrosis microbes and hypertonic salineIn this issue of Cell Host & Microbe, Steinberg et al. present a microbial gene atlas of nasopharyngeal swabs in infants with cystic fibrosis and healthy controls using shotgun metagenomic sequencing....

bit.lyExome sequencing directly implicates 68 genes in inflammatory bowel diseaseInflammatory bowel disease (IBD) is a chronic immune-mediated disorder of the gastrointestinal tract whose genetic basis is only partly resolved because most risk variants identified by genome-wide as...

18 May

Excited to share this new preprint from a large collaborative effort using #exome + #genome sequencing, moving beyond GWAS to implicate 68 genes in #IBD through rare protein-coding variation. bit.ly/43h72GA @broadinstitute.org @mgbresearch.bsky.social

cell.comMechanisms of inflammatory bowel diseases: Insights from human genetics and chemical biologyAdvancements in human genetics have catalyzed rapid discovery in immunology. Graham and Xavier review how functional genomics and chemical biology have joined forces to uncover mechanisms of mucosal i...

27 Apr

Excited to share our new @cp-immunity.bsky.social review, discussing how advances in functional genomics and chemical biology are enabling the translation of IBD genetics into mechanistic understanding and new therapeutic hypotheses. www.cell.com/immunity/ful... #IBD #inflammatoryboweldisease

21 Apr

Out now in @cp-cellhostmicrobe.bsky.social! In collaboration with Swiss clinicians, we built the largest nasal microbial gene atlas in infants w/ and w/o cystic fibrosis to date (cont.)

21 Apr

We found and validated in vitro that early-life perturbations (hypertonic saline inhalation therapy) can select for microbial traits linked to salt and antibiotic tolerance. www.cell.com/cell-host-mi... #antibiotics #cysticfibrosis #microbial @broadinstitute.org @mgbresearch.bsky.social

doi.orgPopulation and single‐cell analyses reveal immune cell‐specific expression profiles associated with Alzheimer's disease riskINTRODUCTION Dysregulation of the peripheral immune system may increase Alzheimer's disease (AD) risk, but the underlying cell type-specific mechanisms remain unclear. METHODS We conducted Mendeli...

23 Mar

Our latest work, with Mika Kivimaki's lab, now online @alzdemjournals.bsky.social: we used single-cell and GWAS data to uncover genes in peripheral blood immune cells associated with Alzheimer’s disease. doi.org/10.1002/alz.... @broadinstitute @MGHMolBio @MGBResearchNews #Alzheimers

nature.comMultimodal framework for the joint analysis of single-cell RNA and T cell receptor sequencing data predicts T cell response to cancer immunotherapy - Nature CommunicationsRecent technologies enable joint profiling of T cell RNA and T cell receptor (TCR) sequences at single-cell resolution. The authors here develop a TCR-RNA Integrating Model (TRIM) to predict intra tum...

16 Mar

New work with @CarolineUhler, now online in @natcomms.nature.com! We developed TRIM, a multimodal framework integrating T cell RNA and TCR profiling to predict T cell responses to cancer treatment. www.nature.com/articles/s41... @broadinstitute @MGHMolBio @MGBResearchNews

nature.comMicrobiota-mediated induction of beige adipocytes in response to dietary cues - NatureIn mice, a low-protein diet leads to a gut-microbiota-driven remodelling of adipose tissue towards brown fat, showing that gut microorganisms have a role in detecting and responding to a lack of prote...

4 Mar

New study, in collaboration with Kenya Honda, out now in @nature.com. We show how a low protein diet drives a microbiota-dependent induction of thermogenic brown adipocytes via FXR & FGF21 pathways. www.nature.com/articles/s41...

@mgbresearch.bsky.social @broadinstitute.org

4 Mar

broadinstitute.orgStudy reveals genetic balancing act between autoimmunity and cancer riskResearchers pinpoint genetic factors linked to both higher risk of a common autoimmune disorder and lower cancer risk

Check out this great write-up of a recent study between the @broadinstitute.org , University of Helsinki, and other institutions which has found more than 400 genetic markers that are linked to autoimmune hypothyroidism (AIHT). (1/4) www.broadinstitute.org/news/study-r...

nature.comGenome-wide association analyses of autoimmune hypothyroidism reveal autoimmune and thyroid-specific contributions and an inverse relationship with cancer risk - Nature GeneticsGenome-wide analyses identify 418 independent associations with autoimmune hypothyroidism and classify risk loci into distinct groupings related to systemic autoimmunity and thyroid-specific dysfuncti...

This paper charts a clear path to understanding how genetics can not only find the genetic variants linked to a disease, but also dissect them into clearly distinct groups that represent independent components of the disease. (3/4) www.nature.com/articles/s41...

Thank you to all the authors, including @dalygene.bsky.social and @masakanai.bsky.social for their hard work and contributions! @mgbresearch.bsky.social

By performing a genome-wide association analysis of over 81,000 people with #AIHT in the FinnGen cohort and UK Biobank, the team was also able to distinguish genetic factors related specifically to thyroid biology from those linked to more general autoimmune processes. (2/4)

nature.comMulti-modal skin atlas identifies a multicellular immune-stromal community associated with disrupted cornification and specific T cell expansion in atopic dermatitis - Nature CommunicationsIn atopic dermatitis (AD), skin barrier disruption leads to chronic inflammation. Here, the authors use single-cell sequencing to map human skin, uncovering AD-specific cell states and populations inv...

Excited to share our new study defining the multicellular ecosystem of atopic dermatitis. Integrating >700k single cells from healthy and inflamed skin, we uncover disease-specific immune circuits linked to disrupted keratinocyte differentiation. www.nature.com/articles/s41...

sciencedirect.comIdentifying microbial protease allergens through protein language model-guided homologyEmerging research links the gut, skin, and oral microbiomes to allergies, with serine proteases (SPs) identified as potential allergens. This study le…

23 Feb

(1/2) New paper out now in Cell Systems @cellpress.bsky.social describing development of a deep learning framework to predict allergenic microbial proteases! www.sciencedirect.com/science/arti... @broadinstitute.org @mgbresearch.bsky.social

cell.comIdentifying microbial protease allergens through protein language model-guided homologyThurimella et al. introduce a deep learning framework using protein language models to predict allergenic proteases in the microbiome. The model identified hundreds of candidate allergenic proteases i...

23 Feb

For an in-depth walkthrough, check out this Tweetorial by first author @00kumar.bsky.social bsky.app/profile/00ku...

Kumar Thurimella, PhD@00kumar.bsky.social

1/ Our paper is out today in @cp-cellsystems.bsky.social. We used protein language models and deep learning to identify candidate protease allergens in the human microbiome. www.cell.com/cell-systems...

thexavierlab.bsky.social reposted

Kumar Thurimella, PhD

@00kumar.bsky.social

20 Feb

Replying to @00kumar.bsky.social

7/ Thanks to Elena Wu and senior authors Damian Plichta, @carriesokol.bsky.social, @thexavierlab.bsky.social, Sergio Bacallado. A cross-disciplinary effort across @broadinstitute.org, @massgeneralbrigham.bsky.social, @cam.ac.uk, @cuanschutz.bsky.social, @gatescambridge.bsky.social

ciim-hannover.deCiiM | Symposium 2026Registration is open. Due to limited capacity, early registration is strongly recommended. Once the maximum number of participants is reached, a waiting list will be established.

18 Feb

We’re looking forward to the upcoming 2nd International Conference on Individualized Infection Medicine in Hannover, 19–21 March 2026. Registration is still open! www.ciim-hannover.de/aktuelles/sy...

nature.comTwo-step screen for CARD9 inhibitorsDiscover the world’s best science and medicine | Nature.com

17 Feb

Nice to see our recent CARD9 work covered in @natrevdrugdiscov.nature.com, with a focus on our two-step screening approach for identifying binders of challenging targets. www.nature.com/articles/d41...

cell.comSpatial transcriptomics reveals altered communities and drivers of aberrant epithelia and pro-fibrotic fibroblasts in interstitial lung diseasesUsing single-nucleus RNA sequencing and spatial transcriptomics, Jaiswal et al. identify disease-associated cell communities that include aberrant transitional alveolar epithelium and pro-fibrotic fib...

22 Jan

Excited to share our latest study in Cell Genomics, combining single-nucleus RNA-seq, spatial transcriptomics, and histology to dissect the molecular determinants of lung fibrosis! www.cell.com/cell-genomic... #fibrosis #lung #ILD

22 Jan

Congratulations to Alok and all the authors! @broadinstitute.org @mgbresearch.bsky.social

sciencedirect.comHuman genetics guides the discovery of CARD9 inhibitors with anti-inflammatory activityHuman genetic association studies highlight key genes involved in disease pathology, yet targets identified by these analyses often fall outside the t…

(🧵1/7) New work, now online in @CellCellPress! Using a phased, binder-first strategy, we identified a ligandable pocket on CARD9 and discovered a small-molecule inhibitor of CARD9 inflammatory signaling. www.sciencedirect.com/science/arti...

These studies firmly establish a foundation for development of an inhibitor of CARD9 inflammatory response. More broadly, this approach illustrates a strategy for using human genetics and chemical biology to guide small-molecule discovery against challenging immune targets. (7/7)

@broadinstitute.org @mgbresearch.bsky.social

Using time-resolved FRET (TR-FRET) displacement screens, surface plasmon resonance (SPR), and structure-activity relationship studies we identified a benzodiazepine compound with selective CARD9 binding and cellular activity. (5/7)

The optimized compound blocked CARD9-dependent NFκB activation and cytokine release in human dendritic cells and reduced inflammation in mouse model of fungal infection expressing humanized CARD9 (hCARD9), demonstrating the feasibility of pharmacological targeting of CARD9. (6/7)

In prior work, we leveraged CARD9Δ11 to study CARD9 regulation and identified the E3 ligase TRIM62 as a CARD9-interacting protein that regulates CARD9 activation through post-translational modification. (3/7) www.sciencedirect.com/science/arti...

To explore pharmacological modulation of CARD9, we took a binder-first strategy: a DNA-encoded library screen and subsequent structural studies revealed a ligandable pocket in the CARD9 coiled-coil domain, guiding subsequent chemical exploration. (4/7)

@laurakiessling.bsky.social

CARD9 is a key immune adaptor required for immune responses against fungi and bacteria and is implicated in multiple inflammatory diseases. The truncation variant CARD9Δ11 protects against Crohn’s disease, suggesting CARD9 inhibition as a strategy for therapeutic intervention. (2/7)

thexavierlab.bsky.social reposted

Laura Kiessling

15 Jan

Fun collaboration with @thexavierlab.bsky.social and Ribbeck groups to figure out how this human lectin plays multiple roles in controlling the #microbiome: stabilizing the mucus barrier and reducing bacteria that breach it. news.mit.edu/2026/protein... #glycotime

news.mit.eduA protein found in the GI tract can neutralize many bacteriaMIT researchers found that a protein called intelectin-2 has broad spectrum antimicrobial activity against bacteria found in the GI tract. Additionally, intelectin-2 can crosslink molecules that make ...

thexavierlab.bsky.social@thexavierlab.bsky.social

Amazing work–with potential therapeutic implications–by the @laurakiessling.bsky.social group reveals dual actions of interlectin-2 in stabilizing mucosal barriers and targeting bacteria that escape a compromised barrier www.nature.com/articles/s41...

nature.comIntelectin-2 is a broad-spectrum antimicrobial lectin - Nature CommunicationsIntelectin-2 defends mucosal interfaces by crosslinking mucus and blocking microbial growth. This study reveals that mouse and human intelectin-2 recognizes galactose-rich glycans to bind and target d...