Despite the uncertainty of the current moment, and despite the understandable anxiety created by constant narratives about AI, replacement, and disruption, the reality is much more open, and much more hopeful.
The biggest discoveries are still ahead of us.
The hardest diseases still need to be cured.
The most important tools still need to be built.
And it will take a village: biologists, physicians, chemists, engineers, material scientists, computer scientists, ethicists, builders, communicators, and many others.
If young people can tune out some of the noise and let curiosity take over, there is an enormous amount of meaningful work waiting for them.
Academia feels increasingly like playing Monkey Island, if you miss something as absurd as picking up a rubber chicken with a pulley in the first scene, you only realize much later that you’re stuck and can’t pass to the next stage.
I was interviewed today by @ScienceMagazine about the funding crisis following the ERC announcement. I argued that when a grant rejection can hinge on something small, and you then have to wait years to resubmit, the cost becomes so high that instead of suggesting “high-risk high-gain” plans scientists will prepare more cautious, less ambitious proposals. It turns into a perverse game of simplifying your ideas and trying (unsuccessfully) to predict what an overstretched reviewer pool will find easiest to digest.
"Abrupt change to European funder’s rules leaves researchers shut out | Science | AAAS" https://t.co/MNjHuqzd7Z
🚀 New paper out (Open Access): a same-donor, cross-tissue scRNA-seq + TCR-seq map of T cells across the human **gut–liver–blood axis**.
The gut–liver axis is arguably the body’s most immunologically active interface, where constant exposure to dietary and microbial antigens meets the liver’s high-volume immune filtration. Yet we still poorly understand how individual T-cell clones are connected across multiple organs within the same person via circulation and tissue seeding. Strikingly, even within a single organ the colon’s IEL and lamina propria T-cell compartments behave like distinct ecosystems, showing huge diversity and surprisingly little clonal overlap despite being separated by only microns.
Key takeaways:
📈 Across tissues, highly expanded clones share a core “clonal success” transcriptional signature
🧩 Niche signaling points to **liver-derived ligands shaping colon TRM states** (via integrin-linked axes)
🧭 Tissue-resident programs diverge strongly across sites (colon vs liver), with LP TRMs enriched for interferon-stimulated programs
🔀 **IEL vs lamina propria** clonotype overlap is *modest* → limited exchange between these compartments
🔥 In liver, **MAIT cells dominate the most expanded clonotypes**
If you care about tissue-resident immunity, MAIT biology, or how immune circuits adapt across connected organs, I’d love to hear what resonates (and what you’d want to see next).
👇 Paper link in the comments.
#CellReports #SingleCell #Immunology #TCells #TissueResident #Gut #Liver #humanbiomimetics #JHACH #JHU
Key findings: Distinct tissue-resident T cell phenotypes, limited clonal exchange between gut IELs & LP, & potential liver influence on colon T cells!
New #bioRxiv preprint with @_DougBru ! We explored T cell diversity & clonal dynamics across the human gut-liver-blood axis using single-cell RNA & TCR sequencing of matched samples. 1/3 https://t.co/rhAunBPAuj #immunology#Tcells#scRNAseq
This work highlights the importance of studying human immunity in situ & has implications for understanding tissue-specific diseases. #gutliveraxis#tissueimmunity#humanimmunology
@davidasinclair@Cell_Metabolism Activity of SCFA is context and ratio dependent as well as the metabolic and proliferative state of cells. For example, they can drive excessive T cell effector function including in IBD.
When one’s cover letter says:”I am particularly drawn to this opportunity [specific aspects of the lab ,e.g., its focus in chromatin dynamics or translational applications]. I am confident that my technical expertise aligns well with the goals of your team.”
Our preprint: Systematic Analysis of Human Colorectal Cancer scRNA-seq Revealed Limited Pro-tumoral IL-17 Production Potential in Gamma Delta T Cells https://t.co/QBrm8QLKoh
@forum_gd @_DougBrubaker @MTrapecar#Immunology#gdTcells#Cancer#colorectalcancer
Me: dedicating half a page of the R01 proposal describing the fluidics and perfusion of our system.
Rev 3: major flaw of the approach is the lack of any perfusion….
😂