Congratulations to Alok and all the authors!

@broadinstitute.org @mgbresearch.bsky.social

Spatial transcriptomics reveals altered communities and drivers of aberrant epithelia and pro-fibrotic fibroblasts in interstitial lung diseases Using 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...

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

@broadinstitute.org
@mgbresearch.bsky.social

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)

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)

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)

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)

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...

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)

Human genetics guides the discovery of CARD9 inhibitors with anti-inflammatory activity Human 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...

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

Intelectin-2 is a broad-spectrum antimicrobial lectin - Nature Communications Intelectin-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...

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...

@mgbresearch.bsky.social

Very excited to share our latest work in @Nature integrating single-cell & spatial transcriptomics with bidirectional CRISPR screens to unravel an immune–stromal cell circuit dependent on the transcription factor GLIS3 that regulates intestinal fibrosis during chronic inflammation. Congrats, Vlad!

Microbiome-derived bile acid signatures in early life and their association with islet autoimmunity - PubMed Emerging studies reveal that gut microbes can conjugate diverse amino acids to bile acids, known as microbially conjugated bile acids. However, their regulation and health effects remain unclear. Here, we analyzed early-life microbially conjugated bile acid patterns and their link to islet autoimmun …

New in @NatureComms — collaborative work with the Knip & Orešič labs uncovers microbially conjugated bile acids in early life linked to immune development and type 1 diabetes risk.

pubmed.ncbi.nlm.nih.gov/41339624/

@broadinstitute.org @mgbresearch.bsky.social

IHMC 2026 SEOUL IHMC 2026 SEOUL 사이트입니다.

Register now for the International Human Microbiome Consortium (#IHMC) 2026, June 3–5 in Seoul, Korea!

Join this global gathering of researchers for an exciting program highlighting the latest discoveries in human #microbiome science:

www.ihmc2026seoul.com/html/

Excited to share our new FinnGen single-nucleus multiome preprint! 🧬

We profiled ~10M PBMCs (snRNA-seq + snATAC-seq) from 1,108 Finnish donors to map how genetic variants drive complex disease through chromatin and gene regulation 🧵👇
🔗 Link: www.medrxiv.org/content/10.1...

ICMI 2026 ICMI provides an ideal opportunity to showcase your organization’s products and services and have direct interface with mucosal immunologists from around the globe.

Registration now open for the International Congress of Mucosal Immunology (ICMI) 2026, Jul 13–17 in Montreal, Canada.

www.socmucimm.org/meetings-eve...

Looking forward to being part of this lineup of talks highlighting research at the interface of the immune system and mucosal surfaces!

Check out their findings from paired mother/infant microbiome & disease-specific metagenomic datasets! rdcu.be/eRVYz (2/2)

Kumar Thurimella & co-authors addressed the challenge of functionally annotating uncharacterized microbial enzymes with CAZyLingua, a deep learning model for classifying CAZymes from metagenomics. (1/2)

Solute carrier (SLC) transporters are implicated in many human diseases. In @jclinicalinvest, we show that efavirenz potentiates metal transporter SLC39A8 via a cryptic allosteric pocket—revealing new potential for therapeutic targeting.

www.jci.org/articles/vie...

In Nov issue: rupress.org/jem/issue/22...
@thexavierlab.bsky.social describe the biological function of Ankrd55 in mice, working as a functional modulator of T cell metabolism impacting Th17 responses. Cover shows a colon section of a mouse that received Ankrd55−/− T cells doi.org/10.1084/jem....

Congrats to Jinjin Xu & co-authors – an image from their recent @jem.org article that describes Ankrd55 as a modulator of T cell metabolism impacting Th17 responses was selected for the cover!

Read the study here: rupress.org/jem/article-...

@broadinstitute.org @mgbresearch.bsky.social

Great summary from the @mgbresearch.bsky.social team on our new Science paper about ENS–immune system interactions! Check it out: www.massgeneralbrigham.org/en/about/new...

Regional encoding of enteric nervous system responses to microbiota and type 2 inflammation Enteric neurons are essential regulators of intestinal physiology, yet their responses to varying microbial and immune environments along the intestinal tract and or during challenges remain poorly un...

Check out our new study in @ScienceMagazine! Using single-cell transcriptomics, we profile enteric nervous system responses to the microbiota and inflammation, identifying regulators of motor #neuron states and #gut transit time.

www.science.org/doi/10.1126/...

Congrats to the authors!

@broadinstitute.org
@mgbresearch.bsky.social

Human immunodeficiency virus and antiretroviral therapies exert distinct influences across diverse gut microbiomes - Nature Microbiology Metagenomic analysis of the gut microbiome of people with human immunodeficiency virus (HIV), from three distinct cohorts, revealed infection- and antiretroviral drug-linked alterations, which may con...

Excited to share new work in @NatureMicrobio! Using metagenomics, we show how #HIV infection and treatment shape the gut microbiome across geographic regions & find ART-induced phageome changes linked to inflammation and atherosclerosis.

www.nature.com/articles/s41...

🔦 Spotlight! The Korean Association of Immuologists International 2025 is convening Oct 30th-Nov 1st in Incheon, South Korea. KAI 2025 will address current topics in immunology, encompassing both fundamental research and its application to immunological diseases.

kai2025.kr

Unusual Phospholipids from Morganella morganii Linked to Depression A multifactorial association study detected a probable causal connection between the prevalence of Morganella morganii in the gut microbiome and the incidence of major depressive disorder (MDD) in the...

Our findings offer a new target that could be useful for diagnosing or treating certain cases of depressive disorder. They also provide a roadmap for probing how other members of the gut microbiome influence human health and behavior.

Harvard Medical School 2025 State of the School Address In the 2025 State of the School Address, Dean George Q. Daley described the challenges and opportunities ahead for Harvard Medical School and academic research.

In his “Harvard Medical School 2025 State of the School Address”, Dean George Daley highlighted our collaboration with the Clardy lab studying the connection between the gut microbiome and depression @harvardmed.bsky.social @broadinstitute.org

#vimeo #microbiome #depression #gut