The Kueh lab

BIG ANNOUNCEMENT📣: I haven’t been this excited to be part of something new in 15 years… Thrilled to reveal the passion project I’ve been working on for the past year and a half!🙀🥳 (thread 👇)

Welcome to the Human Immunome—Conversations with Systems Immunologist John Tsang and Human Immunome Project Chair Jane Metcalfe John and Jane are key subjects in my new investigative article for MIT Tech Review and Aventine. The column offers more details and musings on recent dramatic breakthroughs in immunomics

"Imagine if we can apply the same approach across the entire world and start to map to capture the true diversity of the human immune system so we can build predictive models and figure out interventions." 🔆

Don't miss David Ewing Duncan's new substack:
davideduncan.substack.com/p/welcome-to...

Congrats Nik, Julie and Brian!

Distinct T cell functions enable efficient immunoediting and prevent tumor emergence of developing sarcomas Cheung et al. describe efficient T cell control of nascent neoantigen+ and nearby neoantigen-negative sarcoma cells, underlying a ∼50% reduction in tumor penetrance. This otherwise imperceptible immun...

Happy to announce the publication using advanced models to understand how T cells mediate efficient immunoediting in early sarcomas.

This was a collaboration between Julie Cheung and Brian Hunt
in the lab

Thanks to Cancer Cell for publishing our work.

www.cell.com/cancer-cell/...

If the immune system is an army...
...
would you rather rely on one “super warrior” — or on a diverse team of fighters, even if none of them is the single strongest?

I’d go with the team.

Why? Check out our new study, just published in Science Immunology: www.science.org/doi/10.1126/...

@biorxivpreprint.bsky.social STAT3 operates as an inflammation-dependent transcriptional switch @josephsunlab.bsky.social @simongrassmann.bsky.social @mskcancercenter.bsky.social
www.biorxiv.org/content/10.1...

Research Specialist A/B University Overview The University of Pennsylvania, the largest private employer in Philadelphia, is a world-renowned leader in education, research, and innovation. This historic, Ivy League school co...

The Vahedi Lab is seeking a highly motivated Research Specialist A/B to join our dynamic research group studying the mechanisms of immune regulation. Apply here: wd1.myworkdaysite.com/recruiting/u...

Divergent cytokine and transcriptional signatures control functional T follicular helper cell heterogeneity - Nature Immunology Dalit, Tan and colleagues provide a multiomic profile of T follicular helper (TFH) cells responses to diverse pathogens, revealing a blueprint for transcriptional flexibility and new tools to interrog...

Thrilled to have our latest research @wehi-research.bsky.social published in @natimmunol.nature.com
www.nature.com/articles/s41...

This work was an outstanding partnership between talented PhD student Len Dalit (now postdoc, no 🦋) and bioinformatician @chinweetan.bsky.social

Thread below...

One more thing to mention: we are thrilled to be joining the vibrant and growing Systems Immunology community here, led by @tsanglab.bsky.social. There will be much collaborative work with the vision of understanding and rebuilding the immune system from the ground up, so stay tuned!

As we setup our lab here, we will be looking to recruit at all levels, from students and postdocs to research /management personnel. If you are motivated and curious to understand and engineer the immune system, send me a message.

We are sad to leave to @uwbioe.bsky.social‬, UW and Seattle, and are grateful for the wonderful friends, collaborators and colleagues that have gotten to know here over the years. We will miss you all.

Research The immune system is a spatially distributed, whole-body sensory-reactive system that monitors, reacts, and adapts to various stress signals (e.g., tissue

We have some news to share: The Kueh lab is moving to ‪Yale this fall!‬ We will be joining the Yale Center for Systems and Engineering Immunology ‪@yalecsei.bsky.social‬ and the Department of Immunobiology.

medicine.yale.edu/systems-engi...

This week @science.org examines the wonders of the immune system! From molecular defences that co-evolved with pathogens to specialised cells that are intricately linked with physiology, the immune system is attuned to biological sex and different stages of life.

Identification of proliferating neural progenitors in the adult human hippocampus Continuous adult hippocampal neurogenesis is involved in memory formation and mood regulation but is challenging to study in humans. Difficulties finding proliferating progenitor cells called into que...

Woohoo! From superstars ionut and Marta in the Frisén lab! www.science.org/doi/10.1126/... can’t wait to see what the anti-neurogenesis folks say about it 😃

EPIGENETIC HULK READY TO SMASH AGAIN! GET IN LOSERS!

KuehLab on X: "Our latest preprint, on T cell receptor (TCR) signaling by condensate nucleation! This theory + experiment study was led by the brilliant Will White, with Jay Groves @UCB_Chemistry and David Baker @UWproteindesign and @Arielbs100.  (1/n) https://t.co/JGLukouM44" / X Our latest preprint, on T cell receptor (TCR) signaling by condensate nucleation! This theory + experiment study was led by the brilliant Will White, with Jay Groves @UCB_Chemistry and David Baker @UWproteindesign and @Arielbs100.  (1/n) https://t.co/JGLukouM44

For a summary, check out: x.com/Kueh_Lab/sta... (apologies, but this is on the old platform)

Excited to share that our study, on how T cells selectively sense foreign antigens with single-molecule sensitivity, is out! This work was led by the brilliant Will White, and done in collaboration with Jay Groves and David Baker @uwproteindesign.bsky.social

www.pnas.org/doi/10.1073/...

First Phase 2 randomized trial of engineered T cells for a solid tumor—GI cancer— with some encouraging results
www.thelancet.com/journals/lan... @thelancet.com

🚨 New #preprint alert!
We're excited to share our latest work:
"Single-Allele Chromatin Tracing Reveals Genomic Clustering of Paralogous Transcription Factors as a Mechanism for Developmental Robustness in T Cells"🔗 tinyurl.com/4ve26tbd

Congratulations Joe and Endi!

Check out this new study and TCR Tg mouse generated by Endi Santosa @endicytosis.bsky.social. If you are interested in studying classic and inflationary CD8+ T cell memory to MCMV infection, we’re happy to share this mouse, and @laboxenius.bsky.social is extremely generous with her Tg lines as well.

(1/n) New preprint from @claricehongky.bsky.social
Fan Fang Varshini Ramanathan in collab w Jie Liu.

Q: How do we get ultra-high-res 3D genome maps?

A: New deep learning model, Cleopatra.

Cleo trains on Micro-C, fine-tunes on RCMC, and predicts genome-wide 3D maps at ultra-high resolution.

Congratulations @anshulkundaje.bsky.social and co-workers! I'm partial to the composite TF motifs in thymic/immune development but this is a fantastic resource for many fields!

Check out this great resource of single cell multiome data, cell annotations, regulatory DNA models of cell type resolved chromatin accessibility & comprehensive annotation of motifs & sequence syntax for multiple tissues in early human development 1/

1. For the past thirty years I've had the best job in the world.


I've had the opportunity to follow my curiosity; explore the workings of nature and society; mentor students and junior colleagues in the same process; and teach generations of students about it all.

Transcription factor networks disproportionately enrich for heritability of blood cell phenotypes Most phenotype-associated genetic variants map to noncoding regulatory regions of the human genome, but their mechanisms remain elusive in most cases. We developed a highly efficient strategy, Perturb...

Delighted to have our Perturb-multiome paper, led by #JorgeMartinRufino and @hemagene.bsky.social from our lab, published today in @science.org. Please check out this powerful approach to decipher gene regulatory networks enriched for genetic variation: www.science.org/doi/10.1126/...

Trump promised scientific breakthroughs. Researchers say he’s breaking science. NIH funding for biomedical research has abruptly fallen by billions of dollars, with many grant decisions on hold. Trump officials say they’re reviewing the agency.

Powerful new Washington Post story up...

wapo.st/426d9fT

(Gift link)

1/n

NIH Grants Fueled $95 Billion In FY 2024 Economic Activity, Finds New Report National Institutes of Health grants generated almost $95 billion in economic activity nationwide in FY 2024 according to a new report by United for Medical Research.

It’s the economy stupid- “There is no better investment than one that saves lives, supports local economies and drives America’s global leadership in biomedical innovation” www.forbes.com/sites/michae...

Clonal dynamics and somatic evolution of haematopoiesis in mouse - Nature Isolating and studying haematopoietic stem cells in young and aged mice demonstrates evolutionary processes related to blood production and provides a framework for interpreting future work using labo...

Delighted to share my PhD thesis work is now published in @nature.com! This study tracks the journey of blood stem cells in aging mice, examining how the clonal dynmics of blood production change over time. A short 🧵1/n #aging #stemcells #clonalhematopoiesis
www.nature.com/articles/s41...

Autophagy repression by antigen and cytokines shapes mitochondrial, migration and effector machinery in CD8 T cells - Nature Immunology Sinclair et al. combine quantitative proteomics and an autophagy flux reporter to map autophagy substrates and triggers during CD8 T cell differentiation. Proteins degraded and fueled by autophagy in ...

I am overjoyed to present our latest paper on Autophagy in CD8 Tcells!
www.nature.com/articles/s41...
It was, as all ‘sciencing’ is, a huge team effort.

I will try to do it some justice in the following thread 😊 1/n
@cantrell-lab.bsky.social @immpres.bsky.social @ajmhowden.bsky.social