An infant nasal microbial gene atlas uncovers intervention-driven microbiome shifts and salt-resistant pathogen expansion Steinberg 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, ...

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

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.)

Population and single‐cell analyses reveal immune cell‐specific expression profiles associated with Alzheimer's disease risk INTRODUCTION 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...

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

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

@mgbresearch.bsky.social @broadinstitute.org

Microbiota-mediated induction of beige adipocytes in response to dietary cues - Nature In 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...

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...

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

@mgbresearch.bsky.social

Genome-wide association analyses of autoimmune hypothyroidism reveal autoimmune and thyroid-specific contributions and an inverse relationship with cancer risk - Nature Genetics Genome-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...

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)

Study reveals genetic balancing act between autoimmunity and cancer risk Researchers 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...

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...

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

bsky.app/profile/00ku...

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

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

(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

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...

Two-step screen for CARD9 inhibitors Discover the world’s best science and medicine | Nature.com

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...

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!